Sample records for h1n1 influenza vaccine

  1. A(H1N1)pdm09 influenza infection: vaccine inefficiency.

    PubMed

    Friedman, Nehemya; Drori, Yaron; Pando, Rakefet; Glatman-Freedman, Aharona; Sefty, Hanna; Bassal, Ravit; Stein, Yaniv; Shohat, Tamy; Mendelson, Ella; Hindiyeh, Musa; Mandelboim, Michal

    2017-05-16

    The last influenza pandemic, caused by the swine A(H1N1)pdm09 influenza virus, began in North America at 2009. Since then, the World Health Organization (WHO) recommended integration of the swine-based virus A/California/07/2009 strain in yearly vaccinations. Yet, infections with A(H1N1)pdm09 have continued in subsequent years. The reasons for this are currently unknown. During the 2015-2016 influenza season, we noted an increased prevalence of A(H1N1)pdm09 influenza virus infection in Israel. Our phylogenetic analysis indicated that the circulating A(H1N1)pdm09 strains belonged to 6B.1 and 6B.2 clades and differed from the vaccinating strain, with approximately 18 amino acid differences found between the circulating strains and the immunizing A/California/07/2009 strain. Hemmaglutination inhibition (HI) assays demonstrated higher antibodies titer against the A/California/07/2009 vaccinating strain as compared to the circulating Israeli strains. We thus suggest that the current vaccination was not sufficiently effective and propose inclusion of the current circulating A(H1N1)pdm09 influenza viruses in the annual vaccine composition.

  2. Reassortant H1N1 influenza virus vaccines protect pigs against pandemic H1N1 influenza virus and H1N2 swine influenza virus challenge.

    PubMed

    Yang, Huanliang; Chen, Yan; Shi, Jianzhong; Guo, Jing; Xin, Xiaoguang; Zhang, Jian; Wang, Dayan; Shu, Yuelong; Qiao, Chuanling; Chen, Hualan

    2011-09-28

    Influenza A (H1N1) virus has caused human influenza outbreaks in a worldwide pandemic since April 2009. Pigs have been found to be susceptible to this influenza virus under experimental and natural conditions, raising concern about their potential role in the pandemic spread of the virus. In this study, we generated a high-growth reassortant virus (SC/PR8) that contains the hemagglutinin (HA) and neuraminidase (NA) genes from a novel H1N1 isolate, A/Sichuan/1/2009 (SC/09), and six internal genes from A/Puerto Rico/8/34 (PR8) virus, by genetic reassortment. The immunogenicity and protective efficacy of this reassortant virus were evaluated at different doses in a challenge model using a homologous SC/09 or heterologous A/Swine/Guangdong/1/06(H1N2) virus (GD/06). Two doses of SC/PR8 virus vaccine elicited high-titer serum hemagglutination inhibiting (HI) antibodies specific for the 2009 H1N1 virus and conferred complete protection against challenge with either SC/09 or GD/06 virus, with reduced lung lesions and viral shedding in vaccine-inoculated animals compared with non-vaccinated control animals. These results indicated for the first time that a high-growth SC/PR8 reassortant H1N1 virus exhibits properties that are desirable to be a promising vaccine candidate for use in swine in the event of a pandemic H1N1 influenza. Copyright © 2011 Elsevier B.V. All rights reserved.

  3. Characterization of cross protection of Swine-Origin Influenza Virus (S-OIV) H1N1 and reassortant H5N1 influenza vaccine in BALB/c mice given a single-dose vaccination

    PubMed Central

    2013-01-01

    Background Influenza virus has antigen drift and antigen shift effect, vaccination with some influenza vaccine might not induce sufficient immunity for host to the threat of other influenza virus strains. S-OIV H1N1 and H5N1 influenza vaccines in single-dose immunization were evaluated in mice for cross protection to the challenge of A/California/7/2009 H1N1 or NIBRG-14 H5N1 virus. Results Both H1N1 and H5N1 induced significant homologous IgG, HAI, and microneutralization antibody responses in the mice, while only vaccines plus adjuvant produced significant heterogeneous IgG and HAI antibody responses. Both alum and MPLA adjuvants significantly reduced the S-OIV H1N1 vaccine dose required to elicit protective HAI antibody titers from 0.05 μg to 0.001 μg. Vaccines alone did not protect mice from challenge with heterogeneous influenza virus, while H5N1 vaccine plus alum and MPLA adjuvants did. Mouse body weight loss was also less significant in the presence of adjuvant than in the vaccine without adjuvant. Furthermore, both H1N1 and H5N1 lung viral titers of immunized mice were significantly reduced post challenge with homologous viruses. Conclusion Only in the presence of MPLA adjuvant could the H5N1 vaccine significantly reduce mouse lung viral titers post H1N1 virus challenge, and not vice versa. MPLA adjuvant induced cross protection with a single dose vaccination to the challenge of heterogeneous influenza virus in mice. Lung viral titer seemed to be a better indicator compared to IgG, neutralization antibody, and HAI titer to predict survival of mice infected with influenza virus. PMID:23517052

  4. Boosting heterosubtypic neutralization antibodies in recipients of 2009 pandemic H1N1 influenza vaccine.

    PubMed

    Qiu, Chao; Huang, Yang; Wang, Qian; Tian, Di; Zhang, Wanju; Hu, Yunwen; Yuan, Zhenghong; Zhang, Xiaoyan; Xu, Jianqing

    2012-01-01

    A mass vaccination has been implemented to prevent the spread of 2009 pandemic influenza virus in China. Highly limited information is available on whether this vaccine induces cross-reactive neutralization antibodies against other subtypes of influenza viruses. We employed pseudovirus-based assays to analyze heterosubtypic neutralization responses in serum samples of 23 recipients of 2009 pandemic influenza vaccine. One dose of pandemic vaccine not only stimulated good neutralization antibodies against cognate influenza virus 2009 influenza A (H1N1), but also raised broad cross-reactive neutralization activities against seasonal H3N2 and highly pathogenic avian influenza virus H5N1 and lesser to H2N2. The cross-reactive neutralization activities were completely abolished after the removal of immunoglobin G (IgG). In contrast, H1N1 vaccination alone in influenza-naive mice elicited only vigorous homologous neutralizing activities but not cross-reactive neutralization activities. Our data suggest that the cross-reactive neutralization epitopes do exist in this vaccine and could elicit significant cross-reactive neutralizing IgG antibodies in the presence of preexisting responses. The exposure to H1N1 vaccine is likely to modify the hierarchical order of preexisting immune responses to influenza viruses. These findings provide insights into the evolution of human immunity to influenza viruses after experiencing multiple influenza virus infections and vaccinations.

  5. Pandemic influenza A (H1N1) 2009 vaccine: an update.

    PubMed

    Goel, M K; Goel, M; Khanna, P; Mittal, K

    2011-01-01

    The world witnessed a the first influenza pandemic in this century and fourth overall since first flu pandemic was reported during the World War I. The past experiences with influenza viruses and this pandemic of H1N1 place a consider-able strain on health services and resulted in serious illnesses and a large number of deaths. Develop-ing countries were declared more likely to be at risk from the pandemic effects, as they faced the dual problem of highly vulnerable populations and limited resources to respond H1N1. The public health experts agreed that vaccination is the most effective ways to mitigate the negative effects of the pandemic. The vaccines for H1N1 virus have been used in over 40 countries and administered to over 200 million people helped in a great way and on August 10, 2010, World Health Organization (WHO) announced H1N1 to be in postpandemic period. But based on knowledge about past pandemics, the H1N1 (2009) virus is expected to continue to circulate as a seasonal virus and may undergo some agenic-variation. As WHO strongly recommends vaccination, vigilance for regular updating of the composition of influenza vaccines, based on an assessment of the future impact of circulating viruses along with safety surveillance of the vaccines is necessary. This review has been done to take a stock of the currently available H1N1 vaccines and their possible use as public health intervention in the postpandemic period.

  6. Yeast Surface-Displayed H5N1 Avian Influenza Vaccines

    PubMed Central

    Lei, Han; Jin, Sha; Karlsson, Erik; Schultz-Cherry, Stacey

    2016-01-01

    Highly pathogenic H5N1 avian influenza viruses pose a pandemic threat to human health. A rapid vaccine production against fast outbreak is desired. We report, herein, a paradigm-shift influenza vaccine technology by presenting H5N1 hemagglutinin (HA) to the surface of yeast. We demonstrated, for the first time, that the HA surface-presented yeast can be used as influenza vaccines to elicit both humoral and cell-mediated immunity in mice. The HI titer of antisera reached up to 128 in vaccinated mice. A high level of H5N1 HA-specific IgG1 and IgG2a antibody production was detected after boost immunization. Furthermore, we demonstrated that the yeast surface-displayed HA preserves its antigenic sites. It preferentially binds to both avian- and human-type receptors. In addition, the vaccine exhibited high cross-reactivity to both homologous and heterologous H5N1 viruses. A high level production of anti-HA antibodies was detected in the mice five months after vaccination. Finally, our animal experimental results indicated that the yeast vaccine offered complete protection of mice from lethal H5N1 virus challenge. No severe side effect of yeast vaccines was noted in animal studies. This new technology allows for rapid and large-scale production of influenza vaccines for prepandemic preparation. PMID:28078309

  7. H5N1 influenza vaccine induces a less robust neutralizing antibody response than seasonal trivalent and H7N9 influenza vaccines.

    PubMed

    Wong, Sook-San; DeBeauchamp, Jennifer; Zanin, Mark; Sun, Yilun; Tang, Li; Webby, Richard

    2017-01-01

    Conventional inactivated avian influenza vaccines have performed poorly in past vaccine trials, leading to the hypothesis that they are less immunogenic than seasonal influenza vaccines. We tested this hypothesis by comparing the immunogenicity of the H5N1 and H7N9 vaccines (avian influenza vaccines) to a seasonal trivalent inactivated influenza vaccine in naïve ferrets, administered with or without the adjuvants MF59 or AS03. Vaccine immunogenicity was assessed by measuring neutralizing antibody titers against hemagglutinin and neuraminidase and by hemagglutinin -specific IgG levels. Two doses of unadjuvanted vaccines induced low or no HA-specific IgG responses and hemagglutination-inhibiting titers. Adjuvanted vaccines induced comparable IgG-titers, but poorer neutralizing antibody titers for the H5 vaccine. All adjuvanted vaccines elicited detectable anti- neuraminidase -antibodies with the exception of the H5N1 vaccine, likely due to the low amounts of neuraminidase in the vaccine. Overall, the H5N1 vaccine had poorer capacity to induce neutralizing antibodies, but not HA-specific IgG, compared to H7N9 or trivalent inactivated influenza vaccine.

  8. Protective efficacy of an inactivated Eurasian avian-like H1N1 swine influenza vaccine against homologous H1N1 and heterologous H1N1 and H1N2 viruses in mice.

    PubMed

    Sui, Jinyu; Yang, Dawei; Qiao, Chuanling; Xu, Huiyang; Xu, Bangfeng; Wu, Yunpu; Yang, Huanliang; Chen, Yan; Chen, Hualan

    2016-07-19

    Eurasian avian-like H1N1 (EA H1N1) swine influenza viruses are prevalent in pigs in Europe and Asia, but occasionally cause human infection, which raises concern about their pandemic potential. Here, we produced a whole-virus inactivated vaccine with an EA H1N1 strain (A/swine/Guangxi/18/2011, SW/GX/18/11) and evaluated its efficacy against homologous H1N1 and heterologous H1N1 and H1N2 influenza viruses in mice. A strong humoral immune response, which we measured by hemagglutination inhibition (HI) and virus neutralization (VN), was induced in the vaccine-inoculated mice upon challenge. The inactivated SW/GX/18/11 vaccine provided complete protection against challenge with homologous SW/GX/18/11 virus in mice and provided effective protection against challenge with heterologous H1N1 and H1N2 viruses with distinctive genomic combinations. Our findings suggest that this EA H1N1 vaccine can provide protection against both homologous H1N1 and heterologous H1N1 or H1N2 virus infection. As such, it is an excellent vaccine candidate to prevent H1N1 swine influenza. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Acceptance of 2009 H1N1 influenza vaccine among pregnant women in Delaware.

    PubMed

    Drees, Marci; Johnson, Oluwakemi; Wong, Esther; Stewart, Ashley; Ferisin, Stephanie; Silverman, Paul R; Ehrenthal, Deborah B

    2012-04-01

    Due to disproportionately high mortality from 2009 H1N1 influenza, pregnant women were given highest priority for H1N1 vaccination. We surveyed postpartum women to determine vaccine uptake and reasons for lack of vaccination. We performed a cross-sectional survey of postpartum women delivering at our institution from February 1 to April 15, 2010. The 12-question survey ascertained maternal characteristics and vaccination concerns. Among 307 postpartum women, 191 (62%) had received H1N1 vaccination and 98 (32%) had declined. Factors associated with H1N1 vaccination included older age (relative risk [RR] 1.3, 95% confidence interval [CI] 1.1 to 1.5 for age ≥35 years compared with 20 to 34 years), at least college education (RR 1.5, 95% CI 1.3 to 1.8), prior influenza vaccination (RR 1.6, 95% CI 1.3 to 2.0), provider recommendation (RR 3.9, 95% CI 2.1 to 7.4), vaccination of family members (RR 1.6, 95% CI 1.3 to 1.9), and receipt of seasonal influenza vaccination (RR 2.2, 95% CI 1.7 to 2.9). Non-Hispanic black women were less likely to have been vaccinated (RR 0.6, 95% CI 0.5 to 0.8) than non-Hispanic white women. Safety concerns were cited by the majority (66%) of nonvaccinated women. H1N1 vaccine uptake among pregnant women was substantially higher than reported influenza vaccination rates during previous seasons. Safety concerns were the major barrier to vaccination. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  10. A Candidate H1N1 Pandemic Influenza Vaccine Elicits Protective Immunity in Mice

    PubMed Central

    Steitz, Julia; Barlow, Peter G.; Hossain, Jaber; Kim, Eun; Okada, Kaori; Kenniston, Tom; Rea, Sheri; Donis, Ruben O.; Gambotto, Andrea

    2010-01-01

    Background In 2009 a new pandemic disease appeared and spread globally. The recent emergence of the pandemic influenza virus H1N1 first isolated in Mexico and USA raised concerns about vaccine availability. We here report our development of an adenovirus-based influenza H1N1 vaccine tested for immunogenicity and efficacy to confer protection in animal model. Methods We generated two adenovirus(Ad5)-based influenza vaccine candidates encoding the wildtype or a codon-optimized hemagglutinin antigen (HA) from the recently emerged swine influenza isolate A/California/04/2009 (H1N1)pdm. After verification of antigen expression, immunogenicity of the vaccine candidates were tested in a mouse model using dose escalations for subcutaneous immunization. Sera of immunized animals were tested in microneutalization and hemagglutination inhibition assays for the presence of HA-specific antibodies. HA-specific T-cells were measured in IFNγ Elispot assays. The efficiency of the influenza vaccine candidates were evaluated in a challenge model by measuring viral titer in lung and nasal turbinate 3 days after inoculation of a homologous H1N1 virus. Conclusions/Significance A single immunization resulted in robust cellular and humoral immune response. Remarkably, the intensity of the immune response was substantially enhanced with codon-optimized antigen, indicating the benefit of manipulating the genetic code of HA antigens in the context of recombinant influenza vaccine design. These results highlight the value of advanced technologies in vaccine development and deployment in response to infections with pandemic potential. Our study emphasizes the potential of an adenoviral-based influenza vaccine platform with the benefits of speed of manufacture and efficacy of a single dose immunization. PMID:20463955

  11. Effect of Repeated Vaccination With the Same Vaccine Component Against 2009 Pandemic Influenza A(H1N1) Virus.

    PubMed

    Martínez-Baz, Iván; Casado, Itziar; Navascués, Ana; Díaz-González, Jorge; Aguinaga, Aitziber; Barrado, Laura; Delfrade, Josu; Ezpeleta, Carmen; Castilla, Jesús

    2017-03-15

    The 2009 pandemic influenza A(H1N1) (A[H1N1]pdm09) vaccine component has remained unchanged from 2009. We estimate the effectiveness of current and prior inactivated influenza A(H1N1)pdm09 vaccination from influenza seasons 2010-2011 to 2015-2016. Patients attended with influenza-like illness were tested for influenza. Four periods with continued A(H1N1)pdm09 circulation were included in a test-negative design. We enrolled 1278 cases and 2343 controls. As compared to individuals never vaccinated against influenza A(H1N1)pdm09, the highest effectiveness (66%; 95% confidence interval, 49%-78%) was observed in those vaccinated in the current season who had received 1-2 prior doses. The effectiveness was not statistically lower in individuals vaccinated in the current season only (52%) or in those without current vaccination and >2 prior doses (47%). However, the protection was lower in individuals vaccinated in the current season after >2 prior doses (38%; P = .009) or those currently unvaccinated with 1-2 prior doses (10%; P < .001). Current-season vaccination improved the effect in individuals with 1-2 prior doses and did not modify significantly the risk of influenza in individuals with >2 prior doses. Current vaccination or several prior doses were needed for high protection. Despite the decreasing effect of repeated vaccination, current-season vaccination was not inferior to no current-season vaccination. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  12. Seasonal and 2009 H1N1 influenza vaccine uptake, predictors of vaccination and self-reported barriers to vaccination among secondary school teachers and staff

    PubMed Central

    Painter, Julia E; Sales, Jessica M; Morfaw, Christopher; Jones, LaDawna M; Murray, Dennis; Wingood, Gina M; DiClemente, Ralph J; Hughes, James M

    2011-01-01

    Objective Teachers, like healthcare workers, may be a strategic target for influenza immunization programs. Influenza vaccination is critical to protect both teachers and the students they come into contact with. This study assessed factors associated with seasonal and H1N1 influenza vaccine uptake among middle- and high-school teachers. Results Seventy-eight percent of teachers who planned to receive seasonal influenza vaccine and 36% of those who planned to receive H1N1 influenza vaccine at baseline reported that they did so. Seasonal vaccine uptake was significantly associated with perceived severity (odds ratio [OR] 1.57, p = 0.05) and self-efficacy (OR 4.46, p = 0.006). H1N1 vaccine uptake was associated with perceived barriers (OR 0.7, p = 0.014) and social norms (OR 1.39, p = 0.05). The number one reason for both seasonal and H1N1 influenza vaccine uptake was to avoid getting seasonal/H1N1 influenza disease. The number one reason for seasonal influenza vaccine refusal was a concern it would make them sick and for H1N1 influenza vaccine refusal was concern about vaccine side effects. Methods Participants were recruited from two counties in rural Georgia. Data were collected from surveys in September 2009 and May 2010. Multivariate logistic regression was used to assess the association between teachers' attitudes toward seasonal and H1N1 influenza vaccination and vaccine uptake. Conclusions There is a strong association between the intention to be vaccinated against influenza (seasonal or 2009 H1N1) and actual vaccination uptake. Understanding and addressing factors associated with teachers' influenza vaccine uptake may enhance future influenza immunization efforts. PMID:21263225

  13. Cross-protective immunity against influenza A/H1N1 virus challenge in mice immunized with recombinant vaccine expressing HA gene of influenza A/H5N1 virus

    PubMed Central

    2013-01-01

    Background Influenza virus undergoes constant antigenic evolution, and therefore influenza vaccines must be reformulated each year. Time is necessary to produce a vaccine that is antigenically matched to a pandemic strain. A goal of many research works is to produce universal vaccines that can induce protective immunity to influenza A viruses of various subtypes. Despite intensive studies, the precise mechanisms of heterosubtypic immunity (HSI) remain ambiguous. Method In this study, mice were vaccinated with recombinant virus vaccine (rL H5), in which the hemagglutinin (HA) gene of influenza A/H5N1 virus was inserted into the LaSota Newcastle disease virus (NDV) vaccine strain. Following a challenge with influenza A/H1N1 virus, survival rates and lung index of mice were observed. The antibodies to influenza virus were detected using hemagglutination inhibition (HI). The lung viral loads, lung cytokine levels and the percentages of both IFN-γ+CD4+ and IFN-γ+CD8+ T cells in spleen were detected using real-time RT-PCR, ELISA and flow cytometry respectively. Results In comparison with the group of mice given phosphate-buffered saline (PBS), the mice vaccinated with rL H5 showed reductions in lung index and viral replication in the lungs after a challenge with influenza A/H1N1 virus. The antibody titer in group 3 (H1N1-H1N1) was significantly higher than that in other groups which only low levels of antibody were detected. IFN-γ levels increased in both group 1 (rL H5-H1N1) and group 2 (rL H5 + IL-2-H1N1). And the IFN-γ level of group 2 was significantly higher than that of group 1. The percentages of both IFN-γ+CD4+ and IFN-γ+CD8+ T cells in group 1 (rL H5-H1N1) and group 2 (rL H5 + IL-2-H1N1) increased significantly, as measured by flow cytometry. Conclusion After the mice were vaccinated with rL H5, cross-protective immune response was induced, which was against heterosubtypic influenza A/H1N1 virus. To some extent, cross-protective immune response can

  14. Key points in evaluating immunogenicity of pandemic influenza vaccines: A lesson from immunogenicity studies of influenza A(H1N1)pdm09 vaccine.

    PubMed

    Ohfuji, Satoko; Kobayashi, Masayuki; Ide, Yuichiro; Egawa, Yumi; Saito, Tomoko; Kondo, Kyoko; Ito, Kazuya; Kase, Tetsuo; Maeda, Akiko; Fukushima, Wakaba; Hirota, Yoshio

    2017-09-18

    Immunogenicity studies on pandemic influenza vaccine are necessary to inform rapid development and implementation of a vaccine during a pandemic. Thus, strategies for immunogenicity assessment are required. To identify essential factors to consider when evaluating the immunogenicity of pandemic influenza vaccines using the experience in Japan with the influenza A(H1N1)pdm09 vaccine. We conducted a search of observational studies using PubMed and IchushiWeb. Search terms included "influenza vaccine AND (immunogenicity OR immune response) AND Japan AND (2009 OR pdm09) NOT review," and was limited to studies conducted in humans. A total of 33 articles were identified, of which 16 articles met the inclusion criteria. Immunogenicity of the commercially available influenza A(H1N1)pdm09 vaccine satisfied the international criteria for influenza vaccine immunogenicity in all study populations. The most remarkable immune response was observed in junior high school students, while the lowest immune response was observed in hematological malignancy patients. Similar to immunogenicity studies on seasonal influenza vaccines, factors such as patient background (e.g., age, underlying condition, pre-vaccination titer, body mass index, etc.) and study procedure (e.g., concurrent measurement of pre- and post-vaccination antibody titer, effects of infection during the study period) may have affected the assessment of immunogenicity to the influenza A(H1N1)pdm09 vaccine. In addition, prior vaccination with the seasonal influenza vaccine may inhibit antibody induction by the influenza A(H1N1)pdm09 vaccine. This review discusses factors and strategies that must be considered and addressed during immunogenicity assessments of pandemic influenza vaccines, which may provide useful information for future influenza pandemics. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  15. Willingness to accept H1N1 pandemic influenza vaccine: a cross-sectional study of Hong Kong community nurses.

    PubMed

    Wong, Samuel Y S; Wong, Eliza L Y; Chor, Josette; Kung, Kenny; Chan, Paul K S; Wong, Carmen; Griffiths, Sian M

    2010-10-29

    The 2009 pandemic of influenza A (H1N1) infection has alerted many governments to make preparedness plan to control the spread of influenza A (H1N1) infection. Vaccination for influenza is one of the most important primary preventative measures to reduce the disease burden. Our study aims to assess the willingness of nurses who work for the community nursing service (CNS) in Hong Kong on their acceptance of influenza A (H1N1) influenza vaccination. 401 questionnaires were posted from June 24, 2009 to June 30, 2009 to community nurses with 67% response rate. Results of the 267 respondents on their willingness to accept influenza A (H1N1) vaccine were analyzed. Twenty-seven percent of respondents were willing to accept influenza vaccination if vaccines were available. Having been vaccinated for seasonable influenza in the previous 12 months were significantly independently associated with their willingness to accept influenza A (H1N1) vaccination (OR = 4.03; 95% CI: 2.03-7.98). Similar to previous findings conducted in hospital healthcare workers and nurses, we confirmed that the willingness of community nurses to accept influenza A (H1N1) vaccination is low. Future studies that evaluate interventions to address nurses' specific concerns or interventions that aim to raise the awareness among nurses on the importance of influenza A (H1N1) vaccination to protect vulnerable patient populations is needed.

  16. Influenza Virus Vaccines: Lessons from the 2009 H1N1 pandemic

    PubMed Central

    Broadbent, Andrew J.; Subbarao, Kanta

    2011-01-01

    Reflecting on the 2009 H1N1 pandemic, we summarize lessons regarding influenza vaccines that can be applied in the future. The two major challenges to vaccination during the 2009 H1N1 pandemic were timing and availability of vaccine. Vaccines were, however, well-tolerated and immunogenic, with inactivated vaccines containing 15μg of HA generally inducing antibody titers ≥1:40 in adults within 2 weeks of the administration of a single dose. Moreover, the use of oil-in-water adjuvants in Europe permitted dose- reduction, with vaccines containing as little as 3.75 or 7.5μg HA being immunogenic. Case-control studies demonstrated that monovalent 2009 H1N1 vaccines were effective in preventing infection with the 2009 H1N1 virus, but preliminary data suggests that it is important for individuals to be re-immunized annually. PMID:22125588

  17. Influenza Vaccine Effectiveness Against 2009 Pandemic Influenza A(H1N1) Virus Differed by Vaccine Type During 2013–2014 in the United States

    PubMed Central

    Gaglani, Manjusha; Pruszynski, Jessica; Murthy, Kempapura; Clipper, Lydia; Robertson, Anne; Reis, Michael; Chung, Jessie R.; Piedra, Pedro A.; Avadhanula, Vasanthi; Nowalk, Mary Patricia; Zimmerman, Richard K.; Jackson, Michael L.; Jackson, Lisa A.; Petrie, Joshua G.; Ohmit, Suzanne E.; Monto, Arnold S.; McLean, Huong Q.; Belongia, Edward A.; Fry, Alicia M.; Flannery, Brendan

    2016-01-01

    Background. The predominant strain during the 2013–2014 influenza season was 2009 pandemic influenza A(H1N1) virus (A[H1N1]pdm09). This vaccine-component has remained unchanged from 2009. Methods. The US Flu Vaccine Effectiveness Network enrolled subjects aged ≥6 months with medically attended acute respiratory illness (MAARI), including cough, with illness onset ≤7 days before enrollment. Influenza was confirmed by reverse-transcription polymerase chain reaction (RT-PCR). We determined the effectiveness of trivalent or quadrivalent inactivated influenza vaccine (IIV) among subjects ages ≥6 months and the effectiveness of quadrivalent live attenuated influenza vaccine (LAIV4) among children aged 2–17 years, using a test-negative design. The effect of prior receipt of any A(H1N1)pdm09-containing vaccine since 2009 on the effectiveness of current-season vaccine was assessed. Results. We enrolled 5999 subjects; 5637 (94%) were analyzed; 18% had RT-PCR–confirmed A(H1N1)pdm09-related MAARI. Overall, the effectiveness of vaccine against A(H1N1)pdm09-related MAARI was 54% (95% confidence interval [CI], 46%–61%). Among fully vaccinated children aged 2–17 years, the effectiveness of LAIV4 was 17% (95% CI, −39% to 51%) and the effectiveness of IIV was 60% (95% CI, 36%–74%). Subjects aged ≥9 years showed significant residual protection of any prior A(H1N1)pdm09-containing vaccine dose(s) received since 2009, as did children <9 years old considered fully vaccinated by prior season. Conclusions. During 2013–2014, IIV was significantly effective against A(H1N1)pdm09. Lack of LAIV4 effectiveness in children highlights the importance of continued annual monitoring of effectiveness of influenza vaccines in the United States. PMID:26743842

  18. Clinical efficacy of seasonal influenza vaccination: characteristics of two outbreaks of influenza A(H1N1) in immunocompromised patients.

    PubMed

    Helanterä, I; Janes, R; Anttila, V-J

    2018-06-01

    Influenza A(H1N1) causes serious complications in immunocompromised patients. The efficacy of seasonal vaccination in these patients has been questioned. To describe two outbreaks of influenza A(H1N1) in immunocompromised patients. Two outbreaks of influenza A(H1N1) occurred in our institution: on the kidney transplant ward in 2014 including patients early after kidney or simultaneous pancreas-kidney transplantation, and on the oncology ward in 2016 including patients receiving chemotherapy for malignant tumours. Factors leading to these outbreaks and the clinical efficacy of seasonal influenza vaccination were analysed. Altogether 86 patients were exposed to influenza A(H1N1) during the outbreaks, among whom the seasonal influenza vaccination status was unknown in 10. Only three out of 38 vaccinated patients were infected with influenza A(H1N1), compared with 20 out of 38 unvaccinated patients (P = 0.02). The death of one out of 38 vaccinated patients was associated with influenza, compared with seven out of 38 unvaccinated patients (P = 0.06). Shared factors behind the two outbreaks included outdated facilities not designed for the treatment of immunosuppressed patients. Vaccination coverage among patients was low, between 40% and 70% despite vaccination being offered to all patients free of charge. Vaccination coverage of healthcare workers on the transplant ward was low (46%), but, despite high coverage on the oncology ward (92%), the outbreak occurred. Seasonal influenza vaccination was clinically effective with both a reduced risk of influenza infection and a trend towards reduced mortality in these immunocompromised patients. Several possible causes were identified behind these two outbreaks, requiring continuous awareness in healthcare professionals to prevent further outbreaks. Copyright © 2017 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

  19. Vaccination and auto-immune rheumatic diseases: lessons learnt from the 2009 H1N1 influenza virus vaccination campaign.

    PubMed

    Touma, Zahi; Gladman, Dafna D; Urowitz, Murray B

    2013-03-01

    To determine the safety and efficacy of adjuvant and nonadjuvant influenza A/H1NI vaccination in patients with rheumatic diseases. Due to immune abnormalities and the use of steroids and immunosuppressant treatment, patients with rheumatic diseases are susceptible to infections including influenza. Infections continue to be one of the leading causes of morbidity and mortality in rheumatic diseases, partly due to the disease processes and partly due to medications. Viral infections are particularly an issue, so vaccinations would be advisable. However, because of the abnormalities in immune mechanisms in many rheumatic diseases, it is not clear whether vaccinations are well tolerated and effective. A number of studies confirmed the efficacy and safety of adjuvant and nonadjuvant influenza A/H1NI vaccination in patients with rheumatic diseases. The potential side effects associated with H1N1 vaccines were not different from those observed with seasonal influenza vaccine. The use of steroids and immunosuppressant therapies may alter the efficacy of the vaccines. Adjuvant and nonadjuvant influenza A/H1NI vaccinations have no clinically important effect on production or levels of autoantibodies in patients with rheumatic diseases. H1N1 vaccination should be given to patients with rheumatic diseases.

  20. Efficacy of a pandemic (H1N1) 2009 virus vaccine in pigs against the pandemic influenza virus is superior to commercially available swine influenza vaccines.

    PubMed

    Loeffen, W L A; Stockhofe, N; Weesendorp, E; van Zoelen-Bos, D; Heutink, R; Quak, S; Goovaerts, D; Heldens, J G M; Maas, R; Moormann, R J; Koch, G

    2011-09-28

    In April 2009 a new influenza A/H1N1 strain, currently named "pandemic (H1N1) influenza 2009" (H1N1v), started the first official pandemic in humans since 1968. Several incursions of this virus in pig herds have also been reported from all over the world. Vaccination of pigs may be an option to reduce exposure of human contacts with infected pigs, thereby preventing cross-species transfer, but also to protect pigs themselves, should this virus cause damage in the pig population. Three swine influenza vaccines, two of them commercially available and one experimental, were therefore tested and compared for their efficacy against an H1N1v challenge. One of the commercial vaccines is based on an American classical H1N1 influenza strain, the other is based on a European avian H1N1 influenza strain. The experimental vaccine is based on reassortant virus NYMC X179A (containing the hemagglutinin (HA) and neuraminidase (NA) genes of A/California/7/2009 (H1N1v) and the internal genes of A/Puerto Rico/8/34 (H1N1)). Excretion of infectious virus was reduced by 0.5-3 log(10) by the commercial vaccines, depending on vaccine and sample type. Both vaccines were able to reduce virus replication especially in the lower respiratory tract, with less pathological lesions in vaccinated and subsequently challenged pigs than in unvaccinated controls. In pigs vaccinated with the experimental vaccine, excretion levels of infectious virus in nasal and oropharyngeal swabs, were at or below 1 log(10)TCID(50) per swab and lasted for only 1 or 2 days. An inactivated vaccine containing the HA and NA of an H1N1v is able to protect pigs from an infection with H1N1v, whereas swine influenza vaccines that are currently available are of limited efficaciousness. Whether vaccination of pigs against H1N1v will become opportune remains to be seen and will depend on future evolution of this strain in the pig population. Close monitoring of the pig population, focussing on presence and evolution of

  1. Infant Respiratory Outcomes Associated with Prenatal Exposure to Maternal 2009 A/H1N1 Influenza Vaccination.

    PubMed

    Fell, Deshayne B; Wilson, Kumanan; Ducharme, Robin; Hawken, Steven; Sprague, Ann E; Kwong, Jeffrey C; Smith, Graeme; Wen, Shi Wu; Walker, Mark C

    2016-01-01

    Infants are at high risk for influenza illness, but are ineligible for vaccination before 6 months. Transfer of maternal antibodies to the fetus has been demonstrated for 2009 A/H1N1 pandemic vaccines; however, clinical effectiveness is unknown. Our objective was to evaluate the association between 2009 A/H1N1 pandemic vaccination during pregnancy and rates of infant influenza and pneumonia. We linked a population-based birth cohort to administrative databases to measure rates of influenza and pneumonia diagnosed during ambulatory physician visits, hospitalizations and emergency department visits during one year of follow-up. We estimated incidence rate ratios and 95% confidence intervals (95% CI) using Poisson regression, comparing infants born to A/H1N1-vaccinated women (vaccine-exposed infants) with unexposed infants, adjusted for confounding using high-dimensional propensity scores. Among 117,335 infants in the study, 36,033 (31%) were born to A/H1N1-vaccinated women. Crude rates of influenza during the pandemic (per 100,000 infant-days) for vaccine-exposed and unexposed infants were similar (2.19, 95% CI: 1.27-3.76 and 3.60, 95% CI: 2.51-5.14, respectively), as were crude rates of influenza and pneumonia combined. We did not observe any significant differences in rates of study outcomes between study groups during the second wave of the 2009 A/H1N1 pandemic, nor during any post-pandemic time period. We observed no difference in rates of study outcomes among infants born to A/H1N1-vaccinated mothers relative to unexposed infants born during the second A/H1N1 pandemic wave; however, due to late availability of the pandemic vaccine, the available follow-up time during the pandemic time period was very limited.

  2. Live attenuated H5N1 vaccine with H9N2 internal genes protects chickens from infections by both Highly Pathogenic H5N1 and H9N2 Influenza Viruses

    PubMed Central

    Nang, Nguyen Tai; Song, Byung Min; Kang, Young Myong; Kim, Heui Man; Kim, Hyun Soo; Seo, Sang Heui

    2012-01-01

    Please cite this paper as: Nang et al. (2013) Live attenuated H5N1 vaccine with H9N2 internal genes protects chickens from infections by both Highly Pathogenic H5N1 and H9N2 Influenza Viruses. Influenza and Other Respiratory Viruses 7(2) 120–131. Background  The highly pathogenic H5N1 and H9N2 influenza viruses are endemic in many countries around the world and have caused considerable economic loss to the poultry industry. Objectives  We aimed to study whether a live attenuated H5N1 vaccine comprising internal genes from a cold‐adapted H9N2 influenza virus could protect chickens from infection by both H5N1 and H9N2 viruses. Methods  We developed a cold‐adapted H9N2 vaccine virus expressing hemagglutinin and neuraminidase derived from the highly pathogenic H5N1 influenza virus using reverse genetics. Results and Conclusions  Chickens immunized with the vaccine were protected from lethal infections with homologous and heterologous H5N1 or H9N2 influenza viruses. Specific antibody against H5N1 virus was detected up to 11 weeks after vaccination (the endpoint of this study). In vaccinated chickens, IgA and IgG antibody subtypes were induced in lung and intestinal tissue, and CD4+ and CD8+ T lymphocytes expressing interferon‐gamma were induced in the splenocytes. These data suggest that a live attenuated H5N1 vaccine with cold‐adapted H9N2 internal genes can protect chickens from infection with H5N1 and H9N2 influenza viruses by eliciting humoral and cellular immunity. PMID:22487301

  3. AF03-adjuvanted and non-adjuvanted pandemic influenza A (H1N1) 2009 vaccines induce strong antibody responses in seasonal influenza vaccine-primed and unprimed mice.

    PubMed

    Caillet, Catherine; Piras, Fabienne; Bernard, Marie-Clotilde; de Montfort, Aymeric; Boudet, Florence; Vogel, Frederick R; Hoffenbach, Agnès; Moste, Catherine; Kusters, Inca

    2010-04-19

    Pandemic influenza vaccines have been manufactured using the A/California/07/2009 (H1N1) strain as recommended by the World Health Organization. We evaluated in mice the immunogenicity of pandemic (H1N1) 2009 vaccine and the impact of prior vaccination against seasonal trivalent influenza vaccines (TIV) on antibody responses against pandemic (H1N1) 2009. In naïve mice, a single dose of unadjuvanted H1N1 vaccine (3 microg of HA) was shown to elicit hemagglutination inhibition (HI) antibody titers >40, a titer associated with protection in humans against seasonal influenza. A second vaccine dose of pandemic (H1N1) 2009 vaccine strongly increased these titers, which were consistently higher in mice previously primed with TIV than in naïve mice. At a low immunization dose (0.3 microg of HA), the AF03-adjuvanted vaccine elicited higher HI antibody titers than the corresponding unadjuvanted vaccines in both naïve and TIV-primed animals, suggesting a potential for antigen dose-sparing. These results are in accordance with the use in humans of a split-virion inactivated pandemic (H1N1) 2009 vaccine formulated with or without AF03 adjuvant to protect children and young adults against influenza A (H1N1) 2009 infection. Copyright 2010 Elsevier Ltd. All rights reserved.

  4. Responses to A(H1N1)pdm09 Influenza Vaccines in Participants Previously Vaccinated With Seasonal Influenza Vaccine: A Randomized, Observer-Blind, Controlled Study

    PubMed Central

    Roy-Ghanta, Sumita; Van der Most, Robbert; Li, Ping; Vaughn, David W.

    2014-01-01

    Background. Prior receipt of a trivalent seasonal influenza vaccine (TIV) can affect hemagglutination inhibition (HI) antibody responses to pandemic influenza vaccines. We investigated the effect of TIV priming on humoral responses to AS03-adjuvanted and nonadjuvanted A(H1N1)pdm09 vaccines, the role of AS03 on cell-mediated immune (CMI) responses, and vaccine safety. Methods. Healthy adults (aged 19–40 years) were randomized 1:1:1:1 to receive TIV or saline followed 4 months later by 2 doses, 3 weeks apart, of adjuvanted or nonadjuvanted A(H1N1)pdm09 vaccine and followed up to study end (day 507). Pre- and postvaccination responses of HI and neutralizing antibody, CD4+/CD8+ T cells, memory B cells, and plasmablasts were assessed. Results. Ninety-nine of the 133 participants enrolled completed the study. No vaccine-related serious adverse events were recorded. In TIV-primed participants, A(H1N1)pdm09-specific antibody and CD4+ T-cell and memory B-cell responses to the pandemic vaccine tended to be diminished. Vaccine adjuvantation led to increased responses of vaccine-homologous and -heterologous HI and neutralizing antibodies and CD4+ T cells, homologous memory B cells, and plasmablasts. Conclusions. In healthy adults, prior TIV administration decreased humoral and CMI responses to A(H1N1)pdm09 vaccine. Adjuvantation of A(H1N1)pdm09 antigen helped to overcome immune interference between the influenza vaccines. No safety concerns were observed. Registration. Clinical Trials.gov identifier NCT00707967. PMID:24864125

  5. Protection of human influenza vaccines against a reassortant swine influenza virus of pandemic H1N1 origin using a pig model.

    PubMed

    Arunorat, Jirapat; Charoenvisal, Nataya; Woonwong, Yonlayong; Kedkovid, Roongtham; Jittimanee, Supattra; Sitthicharoenchai, Panchan; Kesdangsakonwut, Sawang; Poolperm, Pariwat; Thanawongnuwech, Roongroje

    2017-10-01

    Since the pandemic H1N1 emergence in 2009 (pdmH1N1), many reassortant pdmH1N1 viruses emerged and found circulating in the pig population worldwide. Currently, commercial human subunit vaccines are used commonly to prevent the influenza symptom based on the WHO recommendation. In case of current reassortant swine influenza viruses transmitting from pigs to humans, the efficacy of current human influenza vaccines is of interest. In this study, influenza A negative pigs were vaccinated with selected commercial human subunit vaccines and challenged with rH3N2. All sera were tested with both HI and SN assays using four representative viruses from the surveillance data in 2012 (enH1N1, pdmH1N1, rH1N2 and rH3N2). The results showed no significant differences in clinical signs and macroscopic and microscopic findings among groups. However, all pig sera from vaccinated groups had protective HI titers to the enH1N1, pdmH1N1 and rH1N2 at 21DPV onward and had protective SN titers only to pdmH1N1and rH1N2 at 21DPV onward. SN test results appeared more specific than those of HI tests. All tested sera had no cross-reactivity against the rH3N2. Both studied human subunit vaccines failed to protect and to stop viral shedding with no evidence of serological reaction against rH3N2. SIV surveillance is essential for monitoring a novel SIV emergence potentially for zoonosis. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Characterization of a whole, inactivated influenza (H5N1) vaccine.

    PubMed

    Tada, Yoshikazu

    2008-11-01

    Effective vaccines against the highly pathogenic influenza A/H5N1 virus are being developed worldwide. In Japan, two adjuvanted, inactivated, whole-virion influenza vaccines were recently developed and licensed as mock-up, pre-pandemic vaccine formulations by the Ministry of Health and Labor Welfare of Japan. During the vaccine design and development process, various obstacles were overcome and, in this report, we introduce the non clinical production, immunogenicity data in human and development process that was associated with egg-derived adjuvanted, inactivated, whole-virion influenza A (H5N1) vaccine. Pilot lots of H5N1 vaccine were produced using the avirulent H5N1 reference strain A/Vietnam/1194/2004 (H5N1) NIBRG-14 and administered following adsorption with aluminum hydroxide as an adjuvant. Quality control and formulation stability tests were performed before clinical trials were initiated (phase I-III). The research foundation for microbial diseases of Osaka University (BIKEN) carried out vaccine production, quality control, stability testing and the phase I clinical trial in addition to overseeing the licensing of this vaccine. Mitsubishi Chemical Safety Institute Ltd. carried out the non clinical pharmacological toxicity and safety studies and the Japanese medical association carried out the phase II/III trials. Phase I-III trials took place in 2006. The production processes were well controlled by established tests and validations. Vaccine quality was confirmed by quality control, stability and pre-clinical tests, and the vaccine was approved as a mock-up, pre-pandemic vaccine by the Ministry of Health and Labor Welfare of Japan. Numerous safety and efficacy procedures were carried out prior to the approval of the described vaccine formulation. Some of these procedures were of particular importance e.g., vaccine development, validation, and quality control tests that included strict monitoring of the hemagglutinin (HA) content of the vaccine

  7. Heterovariant Cross-Reactive B-Cell Responses Induced by the 2009 Pandemic Influenza Virus A Subtype H1N1 Vaccine

    PubMed Central

    He, Xiao-Song; Sasaki, Sanae; Baer, Jane; Khurana, Surender; Golding, Hana; Treanor, John J.; Topham, David J.; Sangster, Mark Y.; Jin, Hong; Dekker, Cornelia L.; Subbarao, Kanta; Greenberg, Harry B.

    2013-01-01

    Background. The generation of heterovariant immunity is a highly desirable feature of influenza vaccines. The goal of this study was to compare the heterovariant B-cell response induced by the monovalent inactivated 2009 pandemic influenza A virus subtype H1N1 (A[H1N1]pdm09) vaccine with that induced by the 2009 seasonal trivalent influenza vaccine (sTIV) containing a seasonal influenza A virus subtype H1N1 (A[H1N1]) component in young and elderly adults. Methods. Plasmablast-derived polyclonal antibodies (PPAb) from young and elderly recipients of A(H1N1)pdm09 vaccine or sTIV were tested for binding activity to various influenza antigens. Results. In A(H1N1)pdm09 recipients, the PPAb titers against homotypic A(H1N1)pdm09 vaccine were similar to those against the heterovariant seasonal A(H1N1) vaccine and were similar between young and elderly subjects. The PPAb avidity was higher among elderly individuals, compared with young individuals. In contrast, the young sTIV recipients had 10-fold lower heterovariant PPAb titers against the A(H1N1)pdm09 vaccine than against the homotypic seasonal A(H1N1) vaccine. In binding assays with recombinant head and stalk domains of hemagglutinin, PPAb from the A(H1N1)pdm09 recipients but not PPAb from the sTIV recipients bound to the conserved stalk domain. Conclusion. The A(H1N1)pdm09 vaccine induced production of PPAb with heterovariant reactivity, including antibodies targeting the conserved hemagglutinin stalk domain. PMID:23107783

  8. H1N1 influenza (Swine flu)

    MedlinePlus

    Swine flu; H1N1 type A influenza ... The H1N1 virus is now considered a regular flu virus. It is one of the three viruses included in the regular (seasonal) flu vaccine . You cannot get H1N1 flu virus from ...

  9. Healthcare workers as parents: attitudes toward vaccinating their children against pandemic influenza A/H1N1.

    PubMed

    Torun, Sebahat D; Torun, Fuat; Catak, Binali

    2010-10-10

    Both the health care workers (HCWs) and children are target groups for pandemic influenza vaccination. The coverage of the target populations is an important determinant for impact of mass vaccination. The objective of this study is to determine the attitudes of HCWs as parents, toward vaccinating their children with pandemic influenza A/H1N1 vaccine. A cross-sectional questionnaire survey was conducted with health care workers (HCWs) in a public hospital during December 2009 in Istanbul. All persons employed in the hospital with or without a health-care occupation are accepted as HCW. The HCWs who are parents of children 6 months to 18 years of age were included in the study. Pearson's chi-square test and logistic regression analysis was applied for the statistical analyses. A total of 389 HCWs who were parents of children aged 6 months-18 years participated study. Among all participants 27.0% (n = 105) reported that themselves had been vaccinated against pandemic influenza A/H1N1. Two third (66.1%) of the parents answered that they will not vaccinate their children, 21.1% already vaccinated and 12.9% were still undecided. Concern about side effect was most reported reason among who had been not vaccinated their children and among undecided parents. The second reason for refusing the pandemic vaccine was concerns efficacy of the vaccine. Media was the only source of information about pandemic influenza in nearly one third of HCWs. Agreement with vaccine safety, self receipt of pandemic influenza A/H1N1 vaccine, and trust in Ministry of Health were found to be associated with the positive attitude toward vaccinating their children against pandemic influenza A/H1N1. Persuading parents to accept a new vaccine seems not be easy even if they are HCWs. In order to overcome the barriers among HCWs related to pandemic vaccines, determination of their misinformation, attitudes and behaviors regarding the pandemic influenza vaccination is necessary. Efforts for orienting

  10. Healthcare workers as parents: attitudes toward vaccinating their children against pandemic influenza A/H1N1

    PubMed Central

    2010-01-01

    Background Both the health care workers (HCWs) and children are target groups for pandemic influenza vaccination. The coverage of the target populations is an important determinant for impact of mass vaccination. The objective of this study is to determine the attitudes of HCWs as parents, toward vaccinating their children with pandemic influenza A/H1N1 vaccine. Methods A cross-sectional questionnaire survey was conducted with health care workers (HCWs) in a public hospital during December 2009 in Istanbul. All persons employed in the hospital with or without a health-care occupation are accepted as HCW. The HCWs who are parents of children 6 months to 18 years of age were included in the study. Pearson's chi-square test and logistic regression analysis was applied for the statistical analyses. Results A total of 389 HCWs who were parents of children aged 6 months-18 years participated study. Among all participants 27.0% (n = 105) reported that themselves had been vaccinated against pandemic influenza A/H1N1. Two third (66.1%) of the parents answered that they will not vaccinate their children, 21.1% already vaccinated and 12.9% were still undecided. Concern about side effect was most reported reason among who had been not vaccinated their children and among undecided parents. The second reason for refusing the pandemic vaccine was concerns efficacy of the vaccine. Media was the only source of information about pandemic influenza in nearly one third of HCWs. Agreement with vaccine safety, self receipt of pandemic influenza A/H1N1 vaccine, and trust in Ministry of Health were found to be associated with the positive attitude toward vaccinating their children against pandemic influenza A/H1N1. Conclusions Persuading parents to accept a new vaccine seems not be easy even if they are HCWs. In order to overcome the barriers among HCWs related to pandemic vaccines, determination of their misinformation, attitudes and behaviors regarding the pandemic influenza vaccination

  11. Design and Characterization of a Computationally Optimized Broadly Reactive Hemagglutinin Vaccine for H1N1 Influenza Viruses

    PubMed Central

    Carter, Donald M.; Darby, Christopher A.; Lefoley, Bradford C.; Crevar, Corey J.; Alefantis, Timothy; Oomen, Raymond; Anderson, Stephen F.; Strugnell, Tod; Cortés-Garcia, Guadalupe; Vogel, Thorsten U.; Parrington, Mark; Kleanthous, Harold

    2016-01-01

    ABSTRACT One of the challenges of developing influenza A vaccines is the diversity of antigenically distinct isolates. Previously, a novel hemagglutinin (HA) for H5N1 influenza was derived from a methodology termed computationally optimized broadly reactive antigen (COBRA). This COBRA HA elicited a broad antibody response against H5N1 isolates from different clades. We now report the development and characterization of a COBRA-based vaccine for both seasonal and pandemic H1N1 influenza virus isolates. Nine prototype H1N1 COBRA HA proteins were developed and tested in mice using a virus-like particle (VLP) format for the elicitation of broadly reactive, functional antibody responses and protection against viral challenge. These candidates were designed to recognize H1N1 viruses isolated within the last 30 years. In addition, several COBRA candidates were designed based on sequences of H1N1 viruses spanning the past 100 years, including modern pandemic H1N1 isolates. Four of the 9 H1N1 COBRA HA proteins (X1, X3, X6, and P1) had the broadest hemagglutination inhibition (HAI) activity against a panel of 17 H1N1 viruses. These vaccines were used in cocktails or prime-boost combinations. The most effective regimens that both elicited the broadest HAI response and protected mice against a pandemic H1N1 challenge were vaccines that contained the P1 COBRA VLP and either the X3 or X6 COBRA VLP vaccine. These mice had little or no detectable viral replication, comparable to that observed with a matched licensed vaccine. This is the first report describing a COBRA-based HA vaccine strategy that elicits a universal, broadly reactive, protective response against seasonal and pandemic H1N1 isolates. IMPORTANCE Universal influenza vaccine approaches have the potential to be paradigm shifting for the influenza vaccine field, with the goal of replacing the current standard of care with broadly cross-protective vaccines. We have used COBRA technology to develop an HA head

  12. Humoral and cellular responses to a non-adjuvanted monovalent H1N1 pandemic influenza vaccine in hospital employees

    PubMed Central

    2013-01-01

    Background The efficacy of the H1N1 influenza vaccine relies on the induction of both humoral and cellular responses. This study evaluated the humoral and cellular responses to a monovalent non-adjuvanted pandemic influenza A/H1N1 vaccine in occupationally exposed subjects who were previously vaccinated with a seasonal vaccine. Methods Sixty healthy workers from a respiratory disease hospital were recruited. Sera and peripheral blood mononuclear cells (PBMCs) were obtained prior to and 1 month after vaccination with a non-adjuvanted monovalent 2009 H1N1 vaccine (Influenza A (H1N1) 2009 Monovalent Vaccine Panenza, Sanofi Pasteur). Antibody titers against the pandemic A/H1N1 influenza virus were measured via hemagglutination inhibition (HI) and microneutralization assays. Antibodies against the seasonal HA1 were assessed by ELISA. The frequency of IFN-γ-producing cells as well as CD4+ and CD8+ T cell proliferation specific to the pandemic virus A/H1N peptides, seasonal H1N1 peptides and seasonal H3N2 peptides were assessed using ELISPOT and flow cytometry. Results At baseline, 6.7% of the subjects had seroprotective antibody titers. The seroconversion rate was 48.3%, and the seroprotection rate was 66.7%. The geometric mean titers (GMTs) were significantly increased (from 6.8 to 64.9, p < 0.05). Forty-nine percent of the subjects had basal levels of specific IFN-γ-producing T cells to the pandemic A/H1N1 peptides that were unchanged post-vaccination. CD4+ T cell proliferation in response to specific pandemic A/H1N1 virus peptides was also unchanged; in contrast, the antigen-specific proliferation of CD8+ T cells significantly increased post-vaccination. Conclusion Our results indicate that a cellular immune response that is cross-reactive to pandemic influenza antigens may be present in populations exposed to the circulating seasonal influenza virus prior to pandemic or seasonal vaccination. Additionally, we found that the pandemic vaccine induced a

  13. Outbreak of Influenza A(H1N1) in a Kidney Transplant Unit-Protective Effect of Vaccination.

    PubMed

    Helanterä, I; Anttila, V-J; Lappalainen, M; Lempinen, M; Isoniemi, H

    2015-09-01

    Seasonal influenza vaccination is recommended for patients with end-stage renal disease (ESRD), despite suggested inferior efficacy among these patients. We characterize an outbreak of influenza A(H1N1) in a kidney transplant unit. Altogether 23 patients were treated on the ward for postoperative care after kidney transplantation during the outbreak. After the first positive case, all patients were tested with nasopharyngeal swab tests and 7 patients were diagnosed with influenza A(H1N1). Altogether 17/23 patients had received adequate seasonal influenza vaccination, of whom 2/17 tested positive for influenza (one asymptomatic, one with mild cough). Five of six unvaccinated patients were diagnosed with influenza A(H1N1); 3/5 suffered from severe respiratory failure and were treated with ventilator support in the ICU, but all died due to acute respiratory distress syndrome, whereas 2/5 suffered from mild viral pneumonitis and recovered fully. The risk of influenza infection and mortality was significantly increased in unvaccinated patients (odds ratio 37.5 [95% CI 2.7-507.5, p = 0.01] and 6.7 [95% CI 2.3-18.9, p = 0.003], respectively). Influenza A(H1N1) had a high mortality in our cohort of nonvaccinated immunosuppressed patients early after kidney transplantation. None of the vaccinated patients developed serious disease, supporting the role of vaccination also for ESRD patients. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

  14. Bell’s palsy and influenza(H1N1)pdm09 containing vaccines: A self-controlled case series

    PubMed Central

    Wijnans, Leonoor; Weibel, Daniel; Sturkenboom, Miriam

    2017-01-01

    Background An association between AS03 adjuvanted pandemic influenza vaccine and the occurrence of Bell’s palsy was found in a population based cohort study in Stockholm, Sweden. To evaluate this association in a different population, we conducted a self-controlled case series in a primary health care database, THIN, in the United Kingdom. The aim of this study was to determine whether there was an increased risk of Bell’s palsy following vaccination with any influenza vaccine containing A/California/7/2009 (H1N1)-like viral strains. Secondly, we investigated whether risks were different following pandemic influenza A(H1N1)pdm09 vaccines and seasonal influenza vaccines containing the influenza A(H1N1)pdm09 strain. Methods The study population comprised all incident Bell’s palsy cases between 1 June 2009 and 30 June 2013 identified in THIN. We determined the relative incidence (RI) of Bell’s palsy during the 6 weeks following vaccination with either pandemic or seasonal influenza vaccine. All analyses were adjusted for seasonality and confounding variables. Results We found an incidence rate of Bell’s palsy of 38.7 per 100,000 person years. Both acute respiratory infection (ARI) consultations and pregnancy were found to be confounders. When adjusted for seasonality, ARI consultations and pregnancies, the RI during the 42 days after vaccination with an influenza vaccine was 0.85 (95% CI: 0.72–1.01). The RI was similar during the 42 days following seasonal vaccine (0.96, 95%CI: 0.82–1.13) or pandemic vaccine (0.73, 95%CI: 0.47–1.12). Conclusion We found no evidence for an increased incidence of Bell’s palsy following seasonal influenza vaccination overall, nor for monovalent pandemic influenza vaccine in 2009. PMID:28467420

  15. Antibody responses to influenza a H1N1 vaccine compared to the circulating strain in influenza vaccine recipients during the 2013/2014 season in North America.

    PubMed

    Barron, Michelle A; Frank, Daniel N; Claypool, David; Ir, Diana; Ning, Mariangeli F; Curtis, Donna; Weinberg, Adriana

    2016-10-01

    Influenza strain A/California/07/2009 H1N1 (H1N1-09) reemerged in 2013/2014 as the predominant cause of illness. We sought to determine if antigenic drift may have contributed to the decreased responses to influenza vaccine. Fifty adults who received trivalent inactivated influenza vaccine (IIV3) and 56 children who received live attenuated quadrivalent influenza vaccine (LAIV4) had hemagglutination inhibition (HAI) and microneutralizing (MN) antibodies measured in plasma against H1N1-09 and H1N1 2013/2014 (H1N1-14) influenza. Partial sequencing of the hemagglutinin gene (nt 280-780) was performed on 38 clinical isolates and the vaccine prototype. In IIV3 recipients, HAI and MN titers against H1N1-14 were significantly lower than against H1N1-09 (p<0.0001 and 0.04, respectively). In LAIV4 recipients, only MN titers were significantly lower (p=0.02) for H1N1-09 compared with H1N1-14. A combined analysis showed significantly lower HAI and MN titers for H1N1-14 compared with H1N1-09 (p=0. 016 and 0.008, respectively). All 38 clinical isolates encoded the HA gene K166Q non-synonymous substitution; other non-synonymous substitutions were observed in <10% of the clinical isolates. 2013/2014 IIV3 and LAIV4 recipients had consistently lower MN antibody titers against H1N1-14 compared with H1N1-09. The HA K166Q mutation, located in a neutralizing epitope, probably contributed to these findings. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Puzzling inefficiency of H5N1 influenza vaccines in Egyptian poultry

    PubMed Central

    Kim, Jeong-Ki; Kayali, Ghazi; Walker, David; Forrest, Heather L.; Ellebedy, Ali H.; Griffin, Yolanda S.; Rubrum, Adam; Bahgat, Mahmoud M.; Kutkat, M. A.; Ali, M. A. A.; Aldridge, Jerry R.; Negovetich, Nicholas J.; Krauss, Scott; Webby, Richard J.; Webster, Robert G.

    2010-01-01

    In Egypt, efforts to control highly pathogenic H5N1 avian influenza virus in poultry and in humans have failed despite increased biosecurity, quarantine, and vaccination at poultry farms. The ongoing circulation of HP H5N1 avian influenza in Egypt has caused >100 human infections and remains an unresolved threat to veterinary and public health. Here, we describe that the failure of commercially available H5 poultry vaccines in Egypt may be caused in part by the passive transfer of maternal H5N1 antibodies to chicks, inhibiting their immune response to vaccination. We propose that the induction of a protective immune response to H5N1 is suppressed for an extended period in young chickens. This issue, among others, must be resolved and additional steps must be taken before the outbreaks in Egypt can be controlled. PMID:20534457

  17. Humans and Ferrets with Prior H1N1 Influenza Virus Infections Do Not Exhibit Evidence of Original Antigenic Sin after Infection or Vaccination with the 2009 Pandemic H1N1 Influenza Virus

    PubMed Central

    O'Donnell, Christopher D.; Wright, Amber; Vogel, Leatrice; Boonnak, Kobporn; Treanor, John J.

    2014-01-01

    The hypothesis of original antigenic sin (OAS) states that the imprint established by an individual's first influenza virus infection governs the antibody response thereafter. Subsequent influenza virus infection results in an antibody response against the original infecting virus and an impaired immune response against the newer influenza virus. The purpose of our study was to seek evidence of OAS after infection or vaccination with the 2009 pandemic H1N1 (2009 pH1N1) virus in ferrets and humans previously infected with H1N1 viruses with various antigenic distances from the 2009 pH1N1 virus, including viruses from 1935 through 1999. In ferrets, seasonal H1N1 priming did not diminish the antibody response to infection or vaccination with the 2009 pH1N1 virus, nor did it diminish the T-cell response, indicating the absence of OAS in seasonal H1N1 virus-primed ferrets. Analysis of paired samples of human serum taken before and after vaccination with a monovalent inactivated 2009 pH1N1 vaccine showed a significantly greater-fold rise in the titer of antibody against the 2009 pH1N1 virus than against H1N1 viruses that circulated during the childhood of each subject. Thus, prior experience with H1N1 viruses did not result in an impairment of the antibody response against the 2009 pH1N1 vaccine. Our data from ferrets and humans suggest that prior exposure to H1N1 viruses did not impair the immune response against the 2009 pH1N1 virus. PMID:24648486

  18. Humans and ferrets with prior H1N1 influenza virus infections do not exhibit evidence of original antigenic sin after infection or vaccination with the 2009 pandemic H1N1 influenza virus.

    PubMed

    O'Donnell, Christopher D; Wright, Amber; Vogel, Leatrice; Boonnak, Kobporn; Treanor, John J; Subbarao, Kanta

    2014-05-01

    The hypothesis of original antigenic sin (OAS) states that the imprint established by an individual's first influenza virus infection governs the antibody response thereafter. Subsequent influenza virus infection results in an antibody response against the original infecting virus and an impaired immune response against the newer influenza virus. The purpose of our study was to seek evidence of OAS after infection or vaccination with the 2009 pandemic H1N1 (2009 pH1N1) virus in ferrets and humans previously infected with H1N1 viruses with various antigenic distances from the 2009 pH1N1 virus, including viruses from 1935 through 1999. In ferrets, seasonal H1N1 priming did not diminish the antibody response to infection or vaccination with the 2009 pH1N1 virus, nor did it diminish the T-cell response, indicating the absence of OAS in seasonal H1N1 virus-primed ferrets. Analysis of paired samples of human serum taken before and after vaccination with a monovalent inactivated 2009 pH1N1 vaccine showed a significantly greater-fold rise in the titer of antibody against the 2009 pH1N1 virus than against H1N1 viruses that circulated during the childhood of each subject. Thus, prior experience with H1N1 viruses did not result in an impairment of the antibody response against the 2009 pH1N1 vaccine. Our data from ferrets and humans suggest that prior exposure to H1N1 viruses did not impair the immune response against the 2009 pH1N1 virus.

  19. Effectiveness of monovalent 2009 pandemic influenza A virus subtype H1N1 and 2010-2011 trivalent inactivated influenza vaccines in Wisconsin during the 2010-2011 influenza season.

    PubMed

    Bateman, Allen C; Kieke, Burney A; Irving, Stephanie A; Meece, Jennifer K; Shay, David K; Belongia, Edward A

    2013-04-15

    The 2009 influenza A virus subtype H1N1 (A[H1N1]pdm09) did not exhibit antigenic drift during the 2010-2011 influenza season, providing an opportunity to investigate the duration of protection after vaccination. We estimated the independent effects of 2010-2011 seasonal trivalent inactivated influenza vaccine (TIV) and A(H1N1)pdm09 vaccine for preventing medically attended influenza A virus infection during the 2010-2011 season. Individuals were tested for influenza A virus by real-time reverse transcription polymerase chain reaction (rRT-PCR) after a clinical encounter for acute respiratory illness. Case-control analyses compared participants with rRT-PCR-confirmed influenza A virus infection and test-negative controls. Vaccine effectiveness was estimated separately for monovalent pandemic vaccine and TIV and was calculated as 100 × [1 - adjusted odds ratio], where the odds ratio was adjusted for potential confounders. The effectiveness of TIV against influenza A virus infection was 63% (95% confidence interval [CI], 37%-78%). The effectiveness of TIV against A(H1N1)pdm09 infection was 77% (95% CI, 44%-90%). Monovalent vaccine administered between October 2009 and April 2010 was not protective during the 2010-2011 season, with an effectiveness of -1% (95% CI, -146% to 59%) against A(H1N1)pdm09 infection.  Monovalent vaccine provided no sustained protection against A(H1N1)pdm09 infection during the 2010-2011 season. This waning effectiveness supports the need for annual revaccination, even in the absence of antigenic drift in A(H1N1)pdm09.

  20. [H1N1 influenza vaccines in Tunisia: efficiency and safety].

    PubMed

    Chaabane, Amel; Aouam, Karim; Ben Fredj, Nadia; Toumi, Adnen; Braham, Dorra; A Boughattas, Naceur; Chakroun, Mohamed

    2011-01-01

    We carried out this study in order to evaluate the effectiveness and the safety of the two H1N1 vaccines available in Tunisia: Focetria(®) and Panenza(®). It's a prospective epidemiological study including 601 vaccinated subjects. The vaccine effectiveness was based on the occurrence of flu clinical symptoms after vaccination. The safety was based on the occurrence of unexpected events after vaccines administration. The vaccines imputability was established according to Begaud et al. method. The number of subjects vaccinated by Focetria(®) is more important than Panenza(®). The efficiency of vaccines would be 93.6%. Neither the medical statue nor the type of the vaccine used influence the occurrence of a flu episode after vaccination. We recorded 406 adverse effects (32.4%) with a high score of imputability (I3). Focetria(®) adverse effects were more frequent than Panenza(®) ones (p = 0.009). Almost all adverse events disappeared within few days. The two vaccines used in Tunisia remain enough efficient to face the influenza (H1N1) pandemia and are well tolerated independently of the demographic and pathological statue of the vaccinated person as well as nature of the vaccine used. © 2011 Société Française de Pharmacologie et de Thérapeutique.

  1. Association Between Pandemic Influenza A(H1N1) Vaccination in Pregnancy and Early Childhood Morbidity in Offspring.

    PubMed

    Hviid, Anders; Svanström, Henrik; Mølgaard-Nielsen, Ditte; Lambach, Philipp

    2017-03-01

    Several studies investigating potential adverse effects of the pandemic A(H1N1) vaccine have supported that influenza A(H1N1) vaccination does not increase the risk for major pregnancy and birth adverse outcomes, but little is known about possible adverse effects in offspring of A(H1N1)-vaccinated mothers beyond the perinatal period and into early childhood. To evaluate whether pandemic influenza A(H1N1) vaccination in pregnancy increases the risk for early childhood morbidity in offspring. Register-based cohort study comprising all live-born singleton children in Denmark from pregnancies overlapping the A(H1N1) influenza vaccination campaign in Denmark, from November 2, 2009, to March 31, 2010. From a cohort of 61 359 pregnancies, offspring exposed and unexposed to the influenza A(H1N1) vaccine during pregnancy were matched 1:4 on propensity scores. Vaccination in pregnancy with a monovalent inactivated AS03-adjuvanted split virion influenza A(H1N1)pdm09 vaccine (Pandemrix; GlaxoSmithKline Biologicals). Rate ratios of hospitalization in early childhood until 5 years of age. Hospitalization was defined as (1) first inpatient hospital admission, (2) all inpatient hospital admissions, and (3) first hospital contact for selected diseases, which included individual infectious diseases and individual neurologic, autoimmune, and behavioral conditions. The mean (SD) age at end of follow-up was 4.6 (0.40) years for the 61 359 children included in the study. In the cohort, the mothers of 55 048 children were unvaccinated, 349 mothers were vaccinated in the first trimester, and 5962 mothers were vaccinated in the second or third trimesters. Children exposed in the first trimester were not more likely to be hospitalized in early childhood than unexposed children (hospitalization rates per 1000 person-years, 300.6 for exposed vs 257.5 for unexposed; rate ratio, 1.17; 95% CI, 0.94-1.45). Similarly, children exposed in the second or third trimester were not more likely to

  2. [Pandemic influenza A (H1N1)v vaccination status and factors affecting vaccination: Ankara and Diyarbakır 2009 data from Turkey].

    PubMed

    Ertek, Mustafa; Sevencan, Funda; Kalaycıoğlu, Handan; Gözalan, Ayşegül; Simşek, Ciğdem; Culha, Gönül; Dorman, Vedat; Ozlü, Ahmet; Arıkan, Füsun; Aktaş, Dilber; Akın, Levent; Korukluoğlu, Gülay; Sevindi, Demet Furkan

    2011-10-01

    In this study, it was aimed to determine the frequency of the symptoms of influenza-like illness during influenza A (H1N1)v pandemic in two provinces where sentinel influenza surveillance was conducted and also to obtain opinions about H1N1 influenza and vaccination, H1N1 vaccination status and factors affecting vaccination. This cross-sectional study was conducted in the provinces of Ankara (capital city, located at Central Anatolia) and Diyarbakır (located at southeastern Anatolia). It was planned to include 455 houses in Ankara and 276 houses in Diyarbakır. The household participation rate in the study was 78.9% and 53.6% for Ankara and Diyarbakır, respectively. Our study was carried out between January-February 2010, with 1164 participants from Ankara and 804 from Diyarbakır, including every household subjects except for infants younger than 11 months and patients with primary/secondary immunodeficiency diseases. Data was collected by site teams consisting of a physician and a healthcare staff with informed consent. Of the participants 45.5% from Ankara and 35.3% from Diyarbakır stated that they had gone through an influenza-like illness. The most frequently indicated clinical symptoms were fatigue/weakness, rhinitis, sore throat and cough. The rates of admission to a physician with influenza like illness complaints were 50.6% and 58.7%; rates of hospitalization due to influenza-like illness were 1% and 1.5%, and rates of antiviral drug use were 3.8% and 1.9%, in Ankara ve Diyarbakır participants, respectively. The rate of personal precautions taken by the subjects for prevention from pandemic influenza were 59% and 53.3%, in Ankara and Diyarbakır, respectively. These precautions most frequently were "hand washing" and "avoiding crowded public areas". H1N1 influenza vaccine was applied in 9.3% of the participants in Ankara and in 3.7% of the participants in Diyarbakır. Vaccination rate was higher in both of the provinces in adults over 25 years old than

  3. Possible Impact of Yearly Childhood Vaccination With Trivalent Inactivated Influenza Vaccine (TIV) on the Immune Response to the Pandemic Strain H1N1.

    PubMed

    Amer, Ahdi; Fischer, Howard; Li, Xiaoming; Asmar, Basim

    2016-03-01

    Annual vaccination of children against seasonal influenza with trivalent inactivated influenza vaccine (TIV) has shown to be beneficial. However, this yearly practice may have unintended effect. Studies have shown that infection with wild type influenza A viruses can stimulate protective heterotypic immunity against unrelated or new influenza subtypes. We hypothesized that a consequence of yearly TIV vaccination is lack of induction of heterotypic immunity against the recent H1N1 pandemic. This was a retrospective case-control study. We reviewed the medical records of polymerase chain reaction-confirmed cases of 2009 H1N1 influenza infection in children 6 months to 18 years and a matched control group seen during the pandemic. We identified 353 polymerase chain reaction-confirmed H1N1 cases and 396 matching control subjects. Among the H1N1 group, 202/353 (57%) cases received a total of 477 doses of seasonal TIV compared with 218/396 (55%) in the control group who received a total of 435 doses. Seasonal TIV uptake was significantly higher in the H1N1 group 477/548 (87%) than in the control group, 435/532 (81%) (P = .017). Seasonal TIV uptake was significantly higher in H1N1-infected group. The finding suggests that the practice of yearly vaccination with TIV might have negatively affected the immune response against the novel pandemic H1N1 strain. Given the rarity of pandemic novel influenza viruses, and the high predictability of seasonal influenza occurrence, the practice of yearly influenza vaccination should be continued. However, the use of live attenuated intranasal vaccine, as opposed to TIV, may allow for the desirable development of a vigorous heterotypic immune response against future pandemics. © The Author(s) 2015.

  4. Antibodies Against the Current Influenza A(H1N1) Vaccine Strain Do Not Protect Some Individuals From Infection With Contemporary Circulating Influenza A(H1N1) Virus Strains.

    PubMed

    Petrie, Joshua G; Parkhouse, Kaela; Ohmit, Suzanne E; Malosh, Ryan E; Monto, Arnold S; Hensley, Scott E

    2016-12-15

    During the 2013-2014 influenza season, nearly all circulating 2009 pandemic influenza A(H1N1) virus (A[H1N1]pdm09) strains possessed an antigenically important mutation in hemagglutinin (K166Q). Here, we performed hemagglutination-inhibition (HAI) assays, using sera collected from 382 individuals prior to the 2013-2014 season, and we determined whether HAI titers were associated with protection from A(H1N1)pdm09 infection. Protection was associated with HAI titers against an A(H1N1)pdm09 strain possessing the K166Q mutation but not with HAI titers against the current A(H1N1)pdm09 vaccine strain, which lacks this mutation. These data indicate that contemporary A(H1N1)pdm09 strains are antigenically distinct from the current A(H1N1)pdm09 vaccine strain. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  5. Influenza vaccination in the Americas: Progress and challenges after the 2009 A(H1N1) influenza pandemic

    PubMed Central

    Ropero-Álvarez, Alba María; El Omeiri, Nathalie; Kurtis, Hannah Jane; Danovaro-Holliday, M. Carolina; Ruiz-Matus, Cuauhtémoc

    2016-01-01

    ABSTRACT Background: There has been considerable uptake of seasonal influenza vaccines in the Americas compared to other regions. We describe the current influenza vaccination target groups, recent progress in vaccine uptake and in generating evidence on influenza seasonality and vaccine effectiveness for immunization programs. We also discuss persistent challenges, 5 years after the A(H1N1) 2009 influenza pandemic. Methods: We compiled and summarized data annually reported by countries to the Pan American Health Organization/World Health Organization (PAHO/WHO) through the WHO/UNICEF joint report form on immunization, information obtained through PAHO's Revolving Fund for Vaccine Procurement and communications with managers of national Expanded Programs on Immunization (EPI). Results: Since 2008, 25 countries/territories in the Americas have introduced new target groups for vaccination or expanded the age ranges of existing target groups. As of 2014, 40 (89%) out of 45 countries/territories have policies established for seasonal influenza vaccination. Currently, 29 (64%) countries/territories target pregnant women for vaccination, the highest priority group according to WHO´s Stategic Advisory Group of Experts and PAHO/WHO's Technical Advisory Group on Vaccine-preventable Diseases, compared to only 7 (16%) in 2008. Among 23 countries reporting coverage data, on average, 75% of adults ≥60 years, 45% of children aged 6–23 months, 32% of children aged 5–2 years, 59% of pregnant women, 78% of healthcare workers, and 90% of individuals with chronic conditions were vaccinated during the 2013–14 Northern Hemisphere or 2014 Southern Hemisphere influenza vaccination activities. Difficulties however persist in the estimation of vaccination coverage, especially for pregnant women and persons with chronic conditions. Since 2007, 6 tropical countries have changed their vaccine formulation from the Northern to the Southern Hemisphere formulation and the timing of

  6. Influenza vaccination in the Americas: Progress and challenges after the 2009 A(H1N1) influenza pandemic.

    PubMed

    Ropero-Álvarez, Alba María; El Omeiri, Nathalie; Kurtis, Hannah Jane; Danovaro-Holliday, M Carolina; Ruiz-Matus, Cuauhtémoc

    2016-08-02

    There has been considerable uptake of seasonal influenza vaccines in the Americas compared to other regions. We describe the current influenza vaccination target groups, recent progress in vaccine uptake and in generating evidence on influenza seasonality and vaccine effectiveness for immunization programs. We also discuss persistent challenges, 5 years after the A(H1N1) 2009 influenza pandemic. We compiled and summarized data annually reported by countries to the Pan American Health Organization/World Health Organization (PAHO/WHO) through the WHO/UNICEF joint report form on immunization, information obtained through PAHO's Revolving Fund for Vaccine Procurement and communications with managers of national Expanded Programs on Immunization (EPI). Since 2008, 25 countries/territories in the Americas have introduced new target groups for vaccination or expanded the age ranges of existing target groups. As of 2014, 40 (89%) out of 45 countries/territories have policies established for seasonal influenza vaccination. Currently, 29 (64%) countries/territories target pregnant women for vaccination, the highest priority group according to WHO´s Stategic Advisory Group of Experts and PAHO/WHO's Technical Advisory Group on Vaccine-preventable Diseases, compared to only 7 (16%) in 2008. Among 23 countries reporting coverage data, on average, 75% of adults ≥60 years, 45% of children aged 6-23 months, 32% of children aged 5-2 years, 59% of pregnant women, 78% of healthcare workers, and 90% of individuals with chronic conditions were vaccinated during the 2013-14 Northern Hemisphere or 2014 Southern Hemisphere influenza vaccination activities. Difficulties however persist in the estimation of vaccination coverage, especially for pregnant women and persons with chronic conditions. Since 2007, 6 tropical countries have changed their vaccine formulation from the Northern to the Southern Hemisphere formulation and the timing of their campaigns to April-May following the

  7. Efficacy of a high-growth reassortant H1N1 influenza virus vaccine against the classical swine H1N1 subtype influenza virus in mice and pigs.

    PubMed

    Wen, Feng; Yu, Hai; Yang, Fu-Ru; Huang, Meng; Yang, Sheng; Zhou, Yan-Jun; Li, Ze-Jun; Tong, Guang-Zhi

    2014-11-01

    Swine influenza (SI) is an acute, highly contagious respiratory disease caused by swine influenza A viruses (SwIVs), and it poses a potential global threat to human health. Classical H1N1 (cH1N1) SwIVs are still circulating and remain the predominant subtype in the swine population in China. In this study, a high-growth reassortant virus (GD/PR8) harboring the hemagglutinin (HA) and neuraminidase (NA) genes from a novel cH1N1 isolate in China, A/Swine/Guangdong/1/2011 (GD/11) and six internal genes from the high-growth A/Puerto Rico/8/34(PR8) virus was generated by plasmid-based reverse genetics and tested as a candidate seed virus for the preparation of an inactivated vaccine. The protective efficacy of this vaccine was evaluated in mice and pigs challenged with GD/11 virus. Prime and boost inoculation of GD/PR8 vaccine yielded high-titer serum hemagglutination inhibiting (HI) antibodies and IgG antibodies for GD/11 in both mice and pigs. Complete protection of mice and pigs against cH1N1 SIV challenge was observed, with significantly fewer lung lesions and reduced viral shedding in vaccine-inoculated animals compared with unvaccinated control animals. Our data demonstrated that the GD/PR8 may serve as the seed virus for a promising SwIVs vaccine to protect the swine population.

  8. Risk of Guillain–Barré syndrome following pandemic influenza A(H1N1) 2009 vaccination in Germany†

    PubMed Central

    Prestel, Jürgen; Volkers, Peter; Mentzer, Dirk; Lehmann, Helmar C; Hartung, Hans-Peter; Keller-Stanislawski, Brigitte

    2014-01-01

    Purpose A prospective, epidemiologic study was conducted to assess whether the 2009 pandemic influenza A(H1N1) vaccination in Germany almost exclusively using an AS03-adjuvanted vaccine (Pandemrix) impacts the risk of Guillain–Barré syndrome (GBS) and its variant Fisher syndrome (FS). Methods Potential cases of GBS/FS were reported by 351 participating hospitals throughout Germany. The self-controlled case series methodology was applied to all GBS/FS cases fulfilling the Brighton Collaboration (BC) case definition (levels 1–3 of diagnostic certainty) with symptom onset between 1 November 2009 and 30 September 2010 reported until end of December 2010. Results Out of 676 GBS/FS reports, in 30 cases, GBS/FS (BC levels 1–3) occurred within 150 days following influenza A(H1N1) vaccination. The relative incidence of GBS/FS within the primary risk period (days 5–42 post-vaccination) compared with the control period (days 43–150 post-vaccination) was 4.65 (95%CI [2.17, 9.98]). Similar results were found when stratifying for infections within 3 weeks prior to onset of GBS/FS and when excluding cases with additional seasonal influenza vaccination. The overall result of temporally adjusted analyses supported the primary finding of an increased relative incidence of GBS/FS following influenza A(H1N1) vaccination. Conclusions The results indicate an increased risk of GBS/FS in temporal association with pandemic influenza A(H1N1) vaccination in Germany. © 2014 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons, Ltd. PMID:24817531

  9. Heterologous Humoral Response against H5N1, H7N3, and H9N2 Avian Influenza Viruses after Seasonal Vaccination in a European Elderly Population

    PubMed Central

    Sanz, Ivan; Rojo, Silvia; Tamames, Sonia; Eiros, José María; Ortiz de Lejarazu, Raúl

    2017-01-01

    Avian influenza viruses are currently one of the main threats to human health in the world. Although there are some screening reports of antibodies against these viruses in humans from Western countries, most of these types of studies are conducted in poultry and market workers of Asian populations. The presence of antibodies against avian influenza viruses was evaluated in an elderly European population. An experimental study was conducted, including pre- and post-vaccine serum samples obtained from 174 elderly people vaccinated with seasonal influenza vaccines of 2006–2007, 2008–2009, 2009–2010, and 2010–2011 Northern Hemisphere vaccine campaigns. The presence of antibodies against A/H5N1, A/H7N3, and A/H9N2 avian influenza viruses were tested by using haemaglutination inhibition assays. Globally, heterotypic antibodies were found before vaccination in 2.9% of individuals against A/H5N1, 1.2% against A/H7N3, and 25.9% against A/H9N2. These pre-vaccination antibodies were present at titers ≥1/40 in 1.1% of individuals against A/H5N1, in 1.1% against H7N3, and in 0.6% against the A/H9N2 subtype. One 76 year-old male showed pre-vaccine antibodies (Abs) against those three avian influenza viruses, and another three individuals presented Abs against two different viruses. Seasonal influenza vaccination induced a significant number of heterotypic seroconversions against A/H5N1 (14.4%) and A/H9N2 (10.9%) viruses, but only one seroconversion was observed against the A/H7N3 subtype. After vaccination, four individuals showed Abs titers ≥1/40 against those three avian viruses, and 55 individuals against both A/H5N1 and A/H9N2. Seasonal vaccination is able to induce some weak heterotypic responses to viruses of avian origin in elderly individuals with no previous exposure to them. However, this response did not accomplish the European Medicament Agency criteria for influenza vaccine efficacy. The results of this study show that seasonal vaccines induce a broad

  10. Seasonal Influenza Vaccine and Protection against Pandemic (H1N1) 2009-Associated Illness among US Military Personnel

    PubMed Central

    Johns, Matthew C.; Eick, Angelia A.; Blazes, David L.; Lee, Seung-eun; Perdue, Christopher L.; Lipnick, Robert; Vest, Kelly G.; Russell, Kevin L.; DeFraites, Robert F.; Sanchez, Jose L.

    2010-01-01

    Introduction A novel A/H1N1 virus is the cause of the present influenza pandemic; vaccination is a key countermeasure, however, few data assessing prior seasonal vaccine effectiveness (VE) against the pandemic strain of H1N1 (pH1N1) virus are available. Materials and Methods Surveillance of influenza-related medical encounter data of active duty military service members stationed in the United States during the period of April–October 2009 with comparison of pH1N1-confirmed cases and location and date-matched controls. Crude odds ratios (OR) and VE estimates for immunized versus non-immunized were calculated as well as adjusted OR (AOR) controlling for sex, age group, and history of prior influenza vaccination. Separate stratified VE analyses by vaccine type (trivalent inactivated [TIV] or live attenuated [LAIV]), age groups and hospitalization status were also performed. For the period of April 20 to October 15, 2009, a total of 1,205 cases of pH1N1-confirmed cases were reported, 966 (80%) among males and over one-half (58%) under 25 years of age. Overall VE for service members was found to be 45% (95% CI, 33 to 55%). Immunization with prior season's TIV (VE = 44%, 95% CI, 32 to 54%) as well as LAIV (VE = 24%, 95% CI, 6 to 38%) were both found to be associated with protection. Of significance, VE against a severe disease outcome was higher (VE = 62%, 95% CI, 14 to 84%) than against milder outcomes (VE = 42%, 95% CI, 29 to 53%). Conclusion A moderate association with protection against clinically apparent, laboratory-confirmed Pandemic (H1N1) 2009-associated illness was found for immunization with either TIV or LAIV 2008–09 seasonal influenza vaccines. This association with protection was found to be especially apparent for severe disease as compared to milder outcome, as well as in the youngest and older populations. Prior vaccination with seasonal influenza vaccines in 2004–08 was also independently associated with protection. PMID:20502705

  11. Pandemic vaccination strategies and influenza severe outcomes during the influenza A(H1N1)pdm09 pandemic and the post-pandemic influenza season: the Nordic experience.

    PubMed

    Gil Cuesta, Julita; Aavitsland, Preben; Englund, Hélène; Gudlaugsson, Ólafur; Hauge, Siri Helene; Lyytikäinen, Outi; Sigmundsdóttir, Guðrún; Tegnell, Anders; Virtanen, Mikko; Krause, Tyra Grove

    2016-04-21

    During the 2009/10 influenza A(H1N1)pdm09 pandemic, the five Nordic countries adopted different approaches to pandemic vaccination. We compared pandemic vaccination strategies and severe influenza outcomes, in seasons 2009/10 and 2010/11 in these countries with similar influenza surveillance systems. We calculated the cumulative pandemic vaccination coverage in 2009/10 and cumulative incidence rates of laboratory confirmed A(H1N1)pdm09 infections, intensive care unit (ICU) admissions and deaths in 2009/10 and 2010/11. We estimated incidence risk ratios (IRR) in a Poisson regression model to compare those indicators between Denmark and the other countries. The vaccination coverage was lower in Denmark (6.1%) compared with Finland (48.2%), Iceland (44.1%), Norway (41.3%) and Sweden (60.0%). In 2009/10 Denmark had a similar cumulative incidence of A(H1N1)pdm09 ICU admissions and deaths compared with the other countries. In 2010/11 Denmark had a significantly higher cumulative incidence of A(H1N1)pdm09 ICU admissions (IRR: 2.4; 95% confidence interval (CI): 1.9-3.0) and deaths (IRR: 8.3; 95% CI: 5.1-13.5). Compared with Denmark, the other countries had higher pandemic vaccination coverage and experienced less A(H1N1)pdm09-related severe outcomes in 2010/11. Pandemic vaccination may have had an impact on severe influenza outcomes in the post-pandemic season. Surveillance of severe outcomes may be used to compare the impact of influenza between seasons and support different vaccination strategies.

  12. Effect of previous and current vaccination against influenza A(H1N1)pdm09, A(H3N2), and B during the post-pandemic period 2010-2016 in Spain.

    PubMed

    Gherasim, Alin; Martínez-Baz, Iván; Castilla, Jesús; Pozo, Francisco; Larrauri, Amparo

    2017-01-01

    Recent studies suggest that the protective effect of the current influenza vaccine could be influenced by vaccination in previous seasons. We estimated the combined effect of the previous and current influenza vaccines from the 2010-2011 season to the 2015-2016 season in Spain. We performed a test-negative case-control study in patients ≥9 years old. We estimated the influenza vaccine effectiveness (IVE) against influenza A(H1N1)pdm09, A(H3N2), and B virus. We included 1206 influenza A(H1N1)pdm09 cases, 1358 A(H3N2) cases and 1079 B cases. IVE against A(H1N1)pdm09 virus in the pooled-season analysis was 53% (95% Confidence Interval (CI): 21% to 72%) for those vaccinated only in the current season and 50% (95%CI: 23% to 68%) for those vaccinated in the both current and previous seasons. Against the influenza A(H3N2) virus, IVE was 17% (95%CI: -43% to 52%) for those vaccinated only in the current season and 3% (95%CI: -33% to 28%) for those vaccinated in both seasons. Regarding influenza B, we obtained similar IVEs for those vaccinated only in the current and those vaccinated in both seasons: 57% (95%CI: 12% to 79%) and 56% (95%CI: 36% to 70%), respectively. Our results suggested no interference between the previous and current influenza vaccines against A(H1N1)pdm09 and B viruses, but a possible negative interference against A(H3N2) virus.

  13. Immediate hypersensitivity reactions following monovalent 2009 pandemic influenza A (H1N1) vaccines: reports to VAERS.

    PubMed

    Halsey, Neal A; Griffioen, Mari; Dreskin, Stephen C; Dekker, Cornelia L; Wood, Robert; Sharma, Devindra; Jones, James F; LaRussa, Philip S; Garner, Jenny; Berger, Melvin; Proveaux, Tina; Vellozzi, Claudia; Broder, Karen; Setse, Rosanna; Pahud, Barbara; Hrncir, David; Choi, Howard; Sparks, Robert; Williams, Sarah Elizabeth; Engler, Renata J; Gidudu, Jane; Baxter, Roger; Klein, Nicola; Edwards, Kathryn; Cano, Maria; Kelso, John M

    2013-12-09

    Hypersensitivity disorders following vaccinations are a cause for concern. To determine the type and rate by age, gender, and vaccine received for reported hypersensitivity reactions following monovalent 2009 pandemic influenza A (H1N1) vaccines. A systematic review of reports to the Vaccine Adverse Event Reporting System (VAERS) following monovalent 2009 pandemic influenza A (H1N1) vaccines. US Civilian reports following vaccine received from October 1, 2009 through May 31, 2010. Age, gender, vaccines received, diagnoses, clinical signs, and treatment were reviewed by nurses and physicians with expertise in vaccine adverse events. A panel of experts, including seven allergists reviewed complex illnesses and those with conflicting evidence for classification of the event. Of 1984 reports, 1286 were consistent with immediate hypersensitivity disorders and 698 were attributed to anxiety reactions, syncope, or other illnesses. The female-to-male ratio was ≥4:1 for persons 20-to-59 years of age, but approximately equal for children under 10. One hundred eleven reports met Brighton Collaboration criteria for anaphylaxis; only one-half received epinephrine for initial therapy. The overall rate of reported hypersensitivity reactions was 10.7 per million vaccine doses distributed, with a 2-fold higher rate for live vaccine. Underreporting, especially of mild events, would result in an underestimate of the true rate of immediate hypersensitivity reactions. Selective reporting of events in adult females could have resulted in higher rates than reported for males. Adult females may be at higher risk of hypersensitivity reactions after influenza vaccination than men. Although the risk of hypersensitivity reactions following 2009 pandemic influenza A (H1N1) vaccines was low, all clinics administering vaccines should be familiar with treatment guidelines for these adverse events, including the use of intramuscular epinephrine early in the course of serious hypersensitivity

  14. Factors Mediating Seasonal and Influenza A (H1N1) Vaccine Acceptance among Ethnically Diverse Populations in the Urban South

    PubMed Central

    Frew, Paula M.; Painter, Julia E.; Hixson, Brooke; Kulb, Carolyn; Moore, Kathryn; del Rio, Carlos; Esteves-Jaramillo, Alejandra; Omer, Saad B.

    2012-01-01

    Objective We examined the acceptability of the influenza A (H1N1) and seasonal vaccinations immediately following government manufacture approval to gauge potential product uptake in minority communities. We studied correlates of vaccine acceptance including attitudes, beliefs, perceptions, and influenza immunization experiences, and sought to identify communication approaches to increase influenza vaccine coverage in community settings. Methods Adults ≥ 18 years participated in a cross-sectional survey from September through December 2009. Venue-based sampling was used to recruit participants of racial and ethnic minorities. Results The sample (N=503) included mostly lower income (81.9%, n=412) participants and African Americans (79.3%, n=399). Respondents expressed greater acceptability of the H1N1 vaccination compared to seasonal flu immunization (t=2.86, p=0.005) although H1N1 vaccine acceptability was moderately low (38%, n=191). Factors associated with acceptance of the H1N1 vaccine included positive attitudes about immunizations [OR=0.23, CI (0.16, 0.33)], community perceptions of H1N1 [OR=2.15, CI (1.57, 2.95)], and having had a flu shot in the past 5 years [OR=2.50, CI (1.52, 4.10). The factors associated with acceptance of the seasonal flu vaccine included positive attitudes about immunization [OR=0.43, CI (0.32, 0.59)], community perceptions of H1N1 [OR=1.53, CI (1.16, 2.01)], and having had the flu shot in the past 5 years [OR=3.53, CI (2.16, 5.78)]. Participants were most likely to be influenced to take a flu shot by physicians [OR=1.94, CI (1.31, 2.86)]. Persons who obtained influenza vaccinations indicated that Facebook (χ2=11.7, p=.02) and Twitter (χ2=18.1, p=.001) could be useful vaccine communication channels and that churches (χ2=21.5, p<.001) and grocery stores (χ2=21.5, p<.001) would be effective “flu shot stops” in their communities. Conclusions In this population, positive vaccine attitudes and community perceptions, along with

  15. Elicitation of Protective Antibodies against a Broad Panel of H1N1 Viruses in Ferrets Preimmune to Historical H1N1 Influenza Viruses.

    PubMed

    Carter, Donald M; Darby, Christopher A; Johnson, Scott K; Carlock, Michael A; Kirchenbaum, Greg A; Allen, James D; Vogel, Thorsten U; Delagrave, Simon; DiNapoli, Joshua; Kleanthous, Harold; Ross, Ted M

    2017-12-15

    Most preclinical animal studies test influenza vaccines in immunologically naive animal models, even though the results of vaccination may not accurately reflect the effectiveness of vaccine candidates in humans that have preexisting immunity to influenza. In this study, novel, broadly reactive influenza vaccine candidates were assessed in preimmune ferrets. These animals were infected with different H1N1 isolates before being vaccinated or infected with another influenza virus. Previously, our group has described the design and characterization of computationally optimized broadly reactive hemagglutinin (HA) antigens (COBRA) for H1N1 isolates. Vaccinating ferrets with virus-like particle (VLP) vaccines expressing COBRA HA proteins elicited antibodies with hemagglutination inhibition (HAI) activity against more H1N1 viruses in the panel than VLP vaccines expressing wild-type HA proteins. Specifically, ferrets infected with the 1986 virus and vaccinated with a single dose of the COBRA HA VLP vaccines elicited antibodies with HAI activity against 11 to 14 of the 15 H1N1 viruses isolated between 1934 and 2013. A subset of ferrets was infected with influenza viruses expressing the COBRA HA antigens. These COBRA preimmune ferrets had superior breadth of HAI activity after vaccination with COBRA HA VLP vaccines than COBRA preimmune ferrets vaccinated with VLP vaccines expressing wild-type HA proteins. Overall, priming naive ferrets with COBRA HA based viruses or using COBRA HA based vaccines to boost preexisting antibodies induced by wild-type H1N1 viruses, COBRA HA antigens elicited sera with the broadest HAI reactivity against multiple antigenic H1N1 viral variants. This is the first report demonstrating the effectiveness of a broadly reactive or universal influenza vaccine in a preimmune ferret model. IMPORTANCE Currently, many groups are testing influenza vaccine candidates to meet the challenge of developing a vaccine that elicits broadly reactive and long

  16. Elicitation of Protective Antibodies against a Broad Panel of H1N1 Viruses in Ferrets Preimmune to Historical H1N1 Influenza Viruses

    PubMed Central

    Carter, Donald M.; Darby, Christopher A.; Johnson, Scott K.; Carlock, Michael A.; Kirchenbaum, Greg A.; Allen, James D.; Vogel, Thorsten U.; Delagrave, Simon; DiNapoli, Joshua; Kleanthous, Harold

    2017-01-01

    ABSTRACT Most preclinical animal studies test influenza vaccines in immunologically naive animal models, even though the results of vaccination may not accurately reflect the effectiveness of vaccine candidates in humans that have preexisting immunity to influenza. In this study, novel, broadly reactive influenza vaccine candidates were assessed in preimmune ferrets. These animals were infected with different H1N1 isolates before being vaccinated or infected with another influenza virus. Previously, our group has described the design and characterization of computationally optimized broadly reactive hemagglutinin (HA) antigens (COBRA) for H1N1 isolates. Vaccinating ferrets with virus-like particle (VLP) vaccines expressing COBRA HA proteins elicited antibodies with hemagglutination inhibition (HAI) activity against more H1N1 viruses in the panel than VLP vaccines expressing wild-type HA proteins. Specifically, ferrets infected with the 1986 virus and vaccinated with a single dose of the COBRA HA VLP vaccines elicited antibodies with HAI activity against 11 to 14 of the 15 H1N1 viruses isolated between 1934 and 2013. A subset of ferrets was infected with influenza viruses expressing the COBRA HA antigens. These COBRA preimmune ferrets had superior breadth of HAI activity after vaccination with COBRA HA VLP vaccines than COBRA preimmune ferrets vaccinated with VLP vaccines expressing wild-type HA proteins. Overall, priming naive ferrets with COBRA HA based viruses or using COBRA HA based vaccines to boost preexisting antibodies induced by wild-type H1N1 viruses, COBRA HA antigens elicited sera with the broadest HAI reactivity against multiple antigenic H1N1 viral variants. This is the first report demonstrating the effectiveness of a broadly reactive or universal influenza vaccine in a preimmune ferret model. IMPORTANCE Currently, many groups are testing influenza vaccine candidates to meet the challenge of developing a vaccine that elicits broadly reactive and long

  17. Relative Efficacy of AS03-Adjuvanted Pandemic Influenza A(H1N1) Vaccine in Children: Results of a Controlled, Randomized Efficacy Trial

    PubMed Central

    Nolan, Terry; Roy-Ghanta, Sumita; Montellano, May; Weckx, Lily; Ulloa-Gutierrez, Rolando; Lazcano-Ponce, Eduardo; Kerdpanich, Angkool; Safadi, Marco Aurélio Palazzi; Cruz-Valdez, Aurelio; Litao, Sandra; Lim, Fong Seng; de Los Santos, Abiel Mascareñas; Weber, Miguel Angel Rodriguez; Tinoco, Juan-Carlos; Mezerville, Marcela Hernandez-de; Faingezicht, Idis; Kosuwon, Pensri; Lopez, Pio; Borja-Tabora, Charissa; Li, Ping; Durviaux, Serge; Fries, Louis; Dubin, Gary; Breuer, Thomas; Innis, Bruce L.; Vaughn, David W.

    2014-01-01

    Background. The vaccine efficacy (VE) of 1 or 2 doses of AS03-adjuvanted influenza A(H1N1) vaccine relative to that of 2 doses of nonadjuvanted influenza A(H1N1) vaccine in children 6 months to <10 years of age in a multinational study conducted during 2010–2011. Methods. A total of 6145 children were randomly assigned at a ratio of 1:1:1 to receive 2 injections 21 days apart of A/California/7/2009(H1N1)-AS03 vaccine at dose 1 and saline placebo at dose 2, 2 doses 21 days apart of A/California/7/2009(H1N1)-AS03 vaccine (the Ad2 group), or 2 doses 21 days apart of nonadjuvanted A/California/7/2009(H1N1) vaccine (the NAd2 group). Active surveillance for influenza-like illnesses continued from days 14 to 385. Nose and throat samples obtained during influenza-like illnesses were tested for A/California/7/2009(H1N1), using reverse-transcriptase polymerase chain reaction. Immunogenicity, reactogenicity, and safety were assessed. Results. There were 23 cases of confirmed 2009 pandemic influenza A(H1N1) (A[H1N1]pdm09) infection for the primary relative VE analysis. The VE in the Ad2 group relative to that in the NAd2 group was 76.8% (95% confidence interval, 18.5%–93.4%). The benefit of the AS03 adjuvant was demonstrated in terms of the greater immunogenicity observed in the Ad2 group, compared with the NAd2 group. Conclusion. The 4–8-fold antigen-sparing adjuvanted pandemic influenza vaccine demonstrated superior and clinically important prevention of A(H1N1)pdm09 infection, compared with nonadjuvanted vaccine, with no observed increase in medically attended or serious adverse events. These data support the use of adjuvanted influenza vaccines during influenza pandemics. Clinical Trials Registration. NCT01051661. PMID:24652494

  18. Effect of previous and current vaccination against influenza A(H1N1)pdm09, A(H3N2), and B during the post-pandemic period 2010-2016 in Spain

    PubMed Central

    Castilla, Jesús; Pozo, Francisco

    2017-01-01

    Background Recent studies suggest that the protective effect of the current influenza vaccine could be influenced by vaccination in previous seasons. We estimated the combined effect of the previous and current influenza vaccines from the 2010–2011 season to the 2015–2016 season in Spain. Methods We performed a test-negative case-control study in patients ≥9 years old. We estimated the influenza vaccine effectiveness (IVE) against influenza A(H1N1)pdm09, A(H3N2), and B virus. Results We included 1206 influenza A(H1N1)pdm09 cases, 1358 A(H3N2) cases and 1079 B cases. IVE against A(H1N1)pdm09 virus in the pooled-season analysis was 53% (95% Confidence Interval (CI): 21% to 72%) for those vaccinated only in the current season and 50% (95%CI: 23% to 68%) for those vaccinated in the both current and previous seasons. Against the influenza A(H3N2) virus, IVE was 17% (95%CI: -43% to 52%) for those vaccinated only in the current season and 3% (95%CI: -33% to 28%) for those vaccinated in both seasons. Regarding influenza B, we obtained similar IVEs for those vaccinated only in the current and those vaccinated in both seasons: 57% (95%CI: 12% to 79%) and 56% (95%CI: 36% to 70%), respectively. Conclusion Our results suggested no interference between the previous and current influenza vaccines against A(H1N1)pdm09 and B viruses, but a possible negative interference against A(H3N2) virus. PMID:28614376

  19. Efficacy of Live-Attenuated H9N2 Influenza Vaccine Candidates Containing NS1 Truncations against H9N2 Avian Influenza Viruses.

    PubMed

    Chen, Sujuan; Zhu, Yinbiao; Yang, Da; Yang, Yang; Shi, Shaohua; Qin, Tao; Peng, Daxin; Liu, Xiufan

    2017-01-01

    H9N2 avian influenza virus is a zoonotic agent with a broad host range that can contribute genetic information to H5 or H7N9 subtype viruses, which are significant threats to both humans and birds. Thus, there is a great need for a vaccine to control H9N2 avian influenza. Three mutant viruses of an H9N2 virus A/chicken/Taixing/10/2010 (rTX-NS1-73, rTX-NS1-100, and rTX-NS1-128) were constructed with different NS1 gene truncations and confirmed by western blot analysis. The genetic stability, pathogenicity, transmissibility, and host immune responses toward these mutants were evaluated. The mutant virus rTX-NS1-128 exhibited the most attenuated phenotype and lost transmissibility. The expression levels of interleukin 12 in the nasal and tracheal tissues from chickens immunized with rTX-NS1-128 were significantly upregulated on day 3 post-immunization and the IgA and IgG antibody levels were significantly increased on days 7, 14, and 21 post-immunization when compared to chickens that received an inactivated vaccine. rTX-NS1-128 also protected chickens from challenge by homologous and heterologous H9N2 avian influenza viruses. The results indicate that rTX-NS1-128 can be used as a potential live-attenuated vaccine against H9N2 avian influenza.

  20. Vaccination with virus-like particles containing H5 antigens from three H5N1 clades protects chickens from H5N1 and H5N8 influenza viruses

    PubMed Central

    Kapczynski, Darrell R.; Tumpey, Terrence M.; Hidajat, Rachmat; Zsak, Aniko; Chrzastek, Klaudia; Tretyakova, Irina; Pushko, Peter

    2016-01-01

    Highly pathogenic avian influenza (HPAI) viruses, especially H5N1 strains, represent a public health threat and cause widespread morbidity and mortality in domestic poultry. Recombinant virus-like particles (VLPs) represent a promising novel vaccine approach to control avian influenza including HPAI strains. Influenza VLPs contain viral hemagglutinin (HA), which can be expressed in cell culture within highly immunogenic VLPs that morphologically and antigenically resemble influenza virions, except VLPs are non-infectious. Here we describe a recombinant VLP containing HA proteins derived from three distinct clades of H5N1 viruses as an experimental, broadly protective H5 avian influenza vaccine. A baculovirus vector was configured to co-express the H5 genes from recent H5N1 HPAI isolates A/chicken/Germany/2014 (clade 2.3.4.4), A/chicken/West Java/Subang/29/2007 (clade 2.1.3) and A/chicken/Egypt/121/2012 (clade 2.2.1). Co-expression of these genes in Sf9 cells along with influenza neuraminidase (NA) and retrovirus gag genes resulted in production of triple-clade H555 VLPs that exhibited hemagglutination activity and morphologically resembled influenza virions. Vaccination of chickens with these VLPs resulted in induction of serum antibody responses and efficient protection against experimental challenges with three different viruses including the recent U.S. H5N8 HPAI isolate. We conclude that these novel triple-clade VLPs represent a feasible strategy for simultaneously evoking protective antibodies against multiple variants of H5 influenza virus. PMID:26868083

  1. Immune Responses in Pigs Vaccinated with Adjuvanted and Non-Adjuvanted A(H1N1)pdm/09 Influenza Vaccines Used in Human Immunization Programmes

    PubMed Central

    Lefevre, Eric A.; Carr, B. Veronica; Inman, Charlotte F.; Prentice, Helen; Brown, Ian H.; Brookes, Sharon M.; Garcon, Fanny; Hill, Michelle L.; Iqbal, Munir; Elderfield, Ruth A.; Barclay, Wendy S.; Gubbins, Simon; Bailey, Mick; Charleston, Bryan

    2012-01-01

    Following the emergence and global spread of a novel H1N1 influenza virus in 2009, two A(H1N1)pdm/09 influenza vaccines produced from the A/California/07/09 H1N1 strain were selected and used for the national immunisation programme in the United Kingdom: an adjuvanted split virion vaccine and a non-adjuvanted whole virion vaccine. In this study, we assessed the immune responses generated in inbred large white pigs (Babraham line) following vaccination with these vaccines and after challenge with A(H1N1)pdm/09 virus three months post-vaccination. Both vaccines elicited strong antibody responses, which included high levels of influenza-specific IgG1 and haemagglutination inhibition titres to H1 virus. Immunisation with the adjuvanted split vaccine induced significantly higher interferon gamma production, increased frequency of interferon gamma-producing cells and proliferation of CD4−CD8+ (cytotoxic) and CD4+CD8+ (helper) T cells, after in vitro re-stimulation. Despite significant differences in the magnitude and breadth of immune responses in the two vaccinated and mock treated groups, similar quantities of viral RNA were detected from the nasal cavity in all pigs after live virus challenge. The present study provides support for the use of the pig as a valid experimental model for influenza infections in humans, including the assessment of protective efficacy of therapeutic interventions. PMID:22427834

  2. Pandemic influenza A (H1N1) 2009 vaccination in children: a UK perspective.

    PubMed

    de Whalley, Philip C S; Pollard, Andrew J

    2013-03-01

    Pandemic H1N1 influenza infection was common in the UK in 2009 and children were particularly vulnerable. Most cases were mild or subclinical, but there was significant mortality, predominantly in those with pre-existing disease. Despite the rapid development of monovalent pandemic vaccines, and the fast-tracked approval process, these products were not available for large-scale use until the end of the second wave of infection. Vaccine uptake was relatively low, both among children and health-care workers. The monovalent pandemic vaccines and the 2010/2011 trivalent seasonal influenza vaccines were immunogenic and effective, and they probably reduced the impact of the third wave of infection. Vaccines containing novel adjuvants enabled antigen sparing, but safety concerns could limit the future use of these adjuvanted influenza vaccines in children. Public perceptions that the threat of the pandemic was exaggerated by the authorities, and concerns about vaccine safety, might prompt an inadequate response to the next influenza pandemic, potentially compromising public health. © 2012 The Authors. Journal of Paediatrics and Child Health © 2012 Paediatrics and Child Health Division (Royal Australasian College of Physicians).

  3. Birth outcomes following immunization of pregnant women with pandemic H1N1 influenza vaccine 2009-2010.

    PubMed

    Eaton, Abigail; Lewis, Ned; Fireman, Bruce; Hansen, John; Baxter, Roger; Gee, Julianne; Klein, Nicola P

    2018-05-03

    Following the H1N1 influenza pandemic in 2009, pregnant women were recommended to receive both seasonal (TIV) and H1N1 influenza vaccines. This study presents incidence of adverse birth and pregnancy outcomes among a population of pregnant women immunized with TIV and H1N1 vaccines at Kaiser Permanente Northern California during 2009-2010. We telephone surveyed pregnant Kaiser Permanente Northern California members to assess non-medically-attended reactions following H1N1, TIV or both vaccines during 2009-2010 (n=5365) in a separate study. Here we assessed preterm birth (<37weeks), very preterm birth (<32weeks), low birth weight (<2500 g, LBW), very low birth weight (<1500g), small for gestational age, spontaneous abortions, stillbirths and congenital anomalies among this cohort by comparing incidence and 95% confidence intervals between the following immunization groups: TIV only, H1N1 only, H1N1 prior to TIV immunization, TIV prior to H1N1 and both immunizations given at the same time. Results did not vary significantly between groups. Comparing H1N1 with TIV, incidence were similar for preterm births (6.37vs 6.28/100 births), very preterm births (5.30vs 8.29/1000 births), LBW (4.19vs 2.90/100 births), very LBW (4.54vs 5.52/1000 births), small for gestational age (9.99vs 9.24/1000 births), spontaneous abortion (7.10vs 6.83/1000 pregnancies), stillbirths (7.10vs 4.57/1000 pregnancies), and congenital anomalies (2.66vs 2.43/100 births). Although constrained by small sample size, complex vaccine groups, and differential vaccine availability during 2009-2010, this study found no difference in adverse birth outcomes between H1N1 vaccine and TIV. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. International collaboration to assess the risk of Guillain Barré Syndrome following Influenza A (H1N1) 2009 monovalent vaccines.

    PubMed

    Dodd, Caitlin N; Romio, Silvana A; Black, Steven; Vellozzi, Claudia; Andrews, Nick; Sturkenboom, Miriam; Zuber, Patrick; Hua, Wei; Bonhoeffer, Jan; Buttery, Jim; Crawford, Nigel; Deceuninck, Genevieve; de Vries, Corinne; De Wals, Philippe; Gutierrez-Gimeno, M Victoria; Heijbel, Harald; Hughes, Hayley; Hur, Kwan; Hviid, Anders; Kelman, Jeffrey; Kilpi, Tehri; Chuang, S K; Macartney, Kristine; Rett, Melisa; Lopez-Callada, Vesta Richardson; Salmon, Daniel; Gimenez-Sanchez, Francisco; Sanz, Nuria; Silverman, Barbara; Storsaeter, Jann; Thirugnanam, Umapathi; van der Maas, Nicoline; Yih, Katherine; Zhang, Tao; Izurieta, Hector

    2013-09-13

    The global spread of the 2009 novel pandemic influenza A (H1N1) virus led to the accelerated production and distribution of monovalent 2009 Influenza A (H1N1) vaccines (pH1N1). This pandemic provided the opportunity to evaluate the risk of Guillain-Barré syndrome (GBS), which has been an influenza vaccine safety concern since the swine flu pandemic of 1976, using a common protocol among high and middle-income countries. The primary objective of this project was to demonstrate the feasibility and utility of global collaboration in the assessment of vaccine safety, including countries both with and without an established infrastructure for vaccine active safety surveillance. A second objective, included a priori, was to assess the risk of GBS following pH1N1 vaccination. The primary analysis used the self-controlled case series (SCCS) design to estimate the relative incidence (RI) of GBS in the 42 days following vaccination with pH1N1 vaccine in a pooled analysis across databases and in analysis using a meta-analytic approach. We found a relative incidence of GBS of 2.42 (95% CI 1.58-3.72) in the 42 days following exposure to pH1N1 vaccine in analysis of pooled data and 2.09 (95% CI 1.28-3.42) using the meta-analytic approach. This study demonstrates that international collaboration to evaluate serious outcomes using a common protocol is feasible. The significance and consistency of our findings support a conclusion of an association between 2009 H1N1 vaccination and GBS. Given the rarity of the event the relative incidence found does not provide evidence in contradiction to international recommendations for the continued use of influenza vaccines. Copyright © 2013 Elsevier Ltd. All rights reserved.

  5. Influence of Birth Cohort on Effectiveness of 2015-2016 Influenza Vaccine Against Medically Attended Illness Due to 2009 Pandemic Influenza A(H1N1) Virus in the United States.

    PubMed

    Flannery, Brendan; Smith, Catherine; Garten, Rebecca J; Levine, Min Z; Chung, Jessie R; Jackson, Michael L; Jackson, Lisa A; Monto, Arnold S; Martin, Emily T; Belongia, Edward A; McLean, Huong Q; Gaglani, Manjusha; Murthy, Kempapura; Zimmerman, Richard; Nowalk, Mary Patricia; Griffin, Marie R; Keipp Talbot, H; Treanor, John J; Wentworth, David E; Fry, Alicia M

    2018-06-20

    The effectiveness of influenza vaccine during 2015-2016 was reduced in some age groups as compared to that in previous 2009 pandemic influenza A(H1N1) virus (A[H1N1]pdm09 virus)-predominant seasons. We hypothesized that the age at first exposure to specific influenza A(H1N1) viruses could influence vaccine effectiveness (VE). We estimated the effectiveness of influenza vaccine against polymerase chain reaction-confirmed influenza A(H1N1)pdm09-associated medically attended illness from the 2010-2011 season through the 2015-2016 season, according to patient birth cohort using data from the Influenza Vaccine Effectiveness Network. Birth cohorts were defined a priori on the basis of likely immunologic priming with groups of influenza A(H1N1) viruses that circulated during 1918-2015. VE was calculated as 100 × [1 - adjusted odds ratio] from logistic regression models comparing the odds of vaccination among influenza virus-positive versus influenza test-negative patients. A total of 2115 A(H1N1)pdm09 virus-positive and 14 696 influenza virus-negative patients aged ≥6 months were included. VE was 61% (95% confidence interval [CI], 56%-66%) against A(H1N1)pdm09-associated illness during the 2010-2011 through 2013-2014 seasons, compared with 47% (95% CI, 36%-56%) during 2015-2016. During 2015-2016, A(H1N1)pdm09-specific VE was 22% (95% CI, -7%-43%) among adults born during 1958-1979 versus 61% (95% CI, 54%-66%) for all other birth cohorts combined. Findings suggest an association between reduced VE against influenza A(H1N1)pdm09-related illness during 2015-2016 and early exposure to specific influenza A(H1N1) viruses.

  6. Antigenic variation of H1N1, H1N2 and H3N2 swine influenza viruses in Japan and Vietnam.

    PubMed

    Takemae, Nobuhiro; Nguyen, Tung; Ngo, Long Thanh; Hiromoto, Yasuaki; Uchida, Yuko; Pham, Vu Phong; Kageyama, Tsutomu; Kasuo, Shizuko; Shimada, Shinichi; Yamashita, Yasutaka; Goto, Kaoru; Kubo, Hideyuki; Le, Vu Tri; Van Vo, Hung; Do, Hoa Thi; Nguyen, Dang Hoang; Hayashi, Tsuyoshi; Matsuu, Aya; Saito, Takehiko

    2013-04-01

    The antigenicity of the influenza A virus hemagglutinin is responsible for vaccine efficacy in protecting pigs against swine influenza virus (SIV) infection. However, the antigenicity of SIV strains currently circulating in Japan and Vietnam has not been well characterized. We examined the antigenicity of classical H1 SIVs, pandemic A(H1N1)2009 (A(H1N1)pdm09) viruses, and seasonal human-lineage SIVs isolated in Japan and Vietnam. A hemagglutination inhibition (HI) assay was used to determine antigenic differences that differentiate the recent Japanese H1N2 and H3N2 SIVs from the H1N1 and H3N2 domestic vaccine strains. Minor antigenic variation between pig A(H1N1)pdm09 viruses was evident by HI assay using 13 mAbs raised against homologous virus. A Vietnamese H1N2 SIV, whose H1 gene originated from a human strain in the mid-2000s, reacted poorly with post-infection ferret serum against human vaccine strains from 2000-2010. These results provide useful information for selection of optimal strains for SIV vaccine production.

  7. Efficacy of a trivalent influenza vaccine against seasonal strains and against 2009 pandemic H1N1: A randomized, placebo-controlled trial.

    PubMed

    Mcbride, William J H; Abhayaratna, Walter P; Barr, Ian; Booy, Robert; Carapetis, Jonathan; Carson, Simon; De Looze, Ferdinandus; Ellis-Pegler, Rod; Heron, Leon; Karrasch, Jeff; Marshall, Helen; Mcvernon, Jodie; Nolan, Terry; Rawlinson, William; Reid, Jim; Richmond, Peter; Shakib, Sepehr; Basser, Russell L; Hartel, Gunter F; Lai, Michael H; Rockman, Steven; Greenberg, Michael E

    2016-09-22

    Before pandemic H1N1 vaccines were available, the potential benefit of existing seasonal trivalent inactivated influenza vaccines (IIV3s) against influenza due to the 2009 pandemic H1N1 influenza strain was investigated, with conflicting results. This study assessed the efficacy of seasonal IIV3s against influenza due to 2008 and 2009 seasonal influenza strains and against the 2009 pandemic H1N1 strain. This observer-blind, randomized, placebo-controlled study enrolled adults aged 18-64years during 2008 and 2009 in Australia and New Zealand. Participants were randomized 2:1 to receive IIV3 or placebo. The primary objective was to demonstrate the efficacy of IIV3 against laboratory-confirmed influenza. Participants reporting an influenza-like illness during the period from 14days after vaccination until 30 November of each study year were tested for influenza by real-time reverse transcription polymerase chain reaction. Over a study period of 2years, 15,044 participants were enrolled (mean age±standard deviation: 35.5±14.7years; 54.4% female). Vaccine efficacy of the 2008 and 2009 IIV3s against influenza due to any strain was 42% (95% confidence interval [CI]: 30%, 52%), whereas vaccine efficacy against influenza due to the vaccine-matched strains was 60% (95% CI: 44%, 72%). Vaccine efficacy of the 2009 IIV3 against influenza due to the 2009 pandemic H1N1 strain was 38% (95% CI: 19%, 53%). No vaccine-related deaths or serious adverse events were reported. Solicited local and systemic adverse events were more frequent in IIV3 recipients than placebo recipients (local: IIV3 74.6% vs placebo 20.4%, p<0.001; systemic: IIV3 46.6% vs placebo 39.1%, p<0.001). The 2008 and 2009 IIV3s were efficacious against influenza due to seasonal influenza strains and the 2009 IIV3 demonstrated moderate efficacy against influenza due to the 2009 pandemic H1N1 strain. Funded by CSL Limited, ClinicalTrials.gov identifier NCT00562484. Copyright © 2016 The Authors. Published by Elsevier

  8. Pre-Existing Cross-Reactive Antibodies to Avian Influenza H5N1 and 2009 Pandemic H1N1 in US Military Personnel

    PubMed Central

    Pichyangkul, Sathit; Krasaesub, Somporn; Jongkaewwattana, Anan; Thitithanyanont, Arunee; Wiboon-ut, Suwimon; Yongvanitchit, Kosol; Limsalakpetch, Amporn; Kum-Arb, Utaiwan; Mongkolsirichaikul, Duangrat; Khemnu, Nuanpan; Mahanonda, Rangsini; Garcia, Jean-Michel; Mason, Carl J.; Walsh, Douglas S.; Saunders, David L.

    2014-01-01

    We studied cross-reactive antibodies against avian influenza H5N1 and 2009 pandemic (p) H1N1 in 200 serum samples from US military personnel collected before the H1N1 pandemic. Assays used to measure antibodies against viral proteins involved in protection included a hemagglutination inhibition (HI) assay and a neuraminidase inhibition (NI) assay. Viral neutralization by antibodies against avian influenza H5N1 and 2009 pH1N1 was assessed by influenza (H5) pseudotyped lentiviral particle-based and H1N1 microneutralization assays. Some US military personnel had cross-neutralizing antibodies against H5N1 (14%) and 2009 pH1N1 (16.5%). The odds of having cross-neutralizing antibodies against 2009 pH1N1 were 4.4 times higher in subjects receiving more than five inactivated whole influenza virus vaccinations than those subjects with no record of vaccination. Although unclear if the result of prior vaccination or disease exposure, these pre-existing antibodies may prevent or reduce disease severity. PMID:24277784

  9. Knowledge, attitudes and anxiety towards influenza A/H1N1 vaccination of healthcare workers in Turkey.

    PubMed

    Savas, Esen; Tanriverdi, Derya

    2010-09-23

    This study aimed to analyze the factors associated with knowledge and attitudes about influenza A (H1N1) and vaccination, and possible relations of these factors with anxiety among healthcare workers (HCW). The study used a cross-sectional descriptive design, and it was carried out between 23 November and 4 December 2009. A total of 300 HCW from two hospitals completed a questionnaire. Data collection tools comprised a questionnaire and the State-Trait Anxiety Inventory (STAI). Vaccination rate for 2009 pandemic influenza A(H1N1) among HCW was low (12.7%). Most of the respondents believed the vaccine was not safe and protective. Vaccination refusal was mostly related to the vaccine's side effects, disbelief to vaccine's protectiveness, negative news about the vaccine and the perceived negative attitude of the Prime Minister to the vaccine. State anxiety was found to be high in respondents who felt the vaccine was unsafe. HCW considered the seriousness of the outbreak, their vaccination rate was low. In vaccination campaigns, governments have to aim at providing trust, and media campaigns should be used to reinforce this trust as well. Accurate reporting by the media of the safety and efficacy of influenza vaccines and the importance of vaccines for the public health would likely have a positive influence on vaccine uptake. Uncertain or negative reporting about the vaccine is detrimental to vaccination efforts.

  10. Acceptance of a vaccine against novel influenza A (H1N1) virus among health care workers in two major cities in Mexico.

    PubMed

    Esteves-Jaramillo, Alejandra; Omer, Saad B; Gonzalez-Diaz, Esteban; Salmon, Daniel A; Hixson, Brooke; Navarro, Francisco; Kawa-Karasik, Simon; Frew, Paula; Morfin-Otero, Rayo; Rodriguez-Noriega, Eduardo; Ramirez, Ylean; Rosas, Araceli; Acosta, Edgar; Varela-Badillo, Vianey; Del Rio, Carlos

    2009-11-01

    Further cases of novel influenza A (H1N1) outbreak are expected in the coming months. Vaccination has been proven to be essential to control a pandemic of influenza; therefore, considerable efforts and resources have been devoted to develop a vaccine against the influenza A (H1N1) virus. With the current availability of the vaccine, it will be important to immunize as many people as possible. However, previous data with seasonal influenza vaccines have shown that there are multiple barriers related to perceptions and attitudes of the population that influence vaccine use. The aim of the study was to evaluate the acceptance of a newly developed vaccine against pandemic (H1N1) 2009 influenza A among healthcare workers (HCW) in Mexico. We conducted a cross-sectional study among HCW in three hospitals in the two largest cities in Mexico-Mexico City and Guadalajara-between June and September 2009. A total of 1097 HCW participated in the survey. Overall, 80% (n = 880) intended to accept the H1N1 pandemic vaccine and 71.6% (n = 786) reported they would recommend the vaccine to their patients. Doctors were more likely to accept and recommend the vaccine than nurses. HCWs who intend to be immunized will be more likely to do so if they know that the vaccine is safe and effective. Knowledge of the willingness to accept the vaccine can be used to plan strategies that will effectively respond to the needs of the population studied, reducing the health and economic impact of novel influenza A (H1N1) virus.

  11. Lessons from pandemic influenza A(H1N1): the research-based vaccine industry's perspective.

    PubMed

    Abelin, Atika; Colegate, Tony; Gardner, Stephen; Hehme, Norbert; Palache, Abraham

    2011-02-01

    As A(H1N1) influenza enters the post-pandemic phase, health authorities around the world are reviewing the response to the pandemic. To ensure this process enhances future preparations, it is essential that perspectives are included from all relevant stakeholders, including vaccine manufacturers. This paper outlines the contribution of R&D-based influenza vaccine producers to the pandemic response, and explores lessons that can be learned to improve future preparedness. The emergence of 2009 A(H1N1) influenza led to unprecedented collaboration between global health authorities, scientists and manufacturers, resulting in the most comprehensive pandemic response ever undertaken, with a number of vaccines approved for use three months after the pandemic declaration. This response was only possible because of the extensive preparations undertaken during the last decade. During this period, manufacturers greatly increased influenza vaccine production capacity, and estimates suggest a further doubling of capacity by 2014. Producers also introduced cell-culture technology, while adjuvant and whole virion technologies significantly reduced pandemic vaccine antigen content. This substantially increased pandemic vaccine production capacity, which in July 2009 WHO estimated reached 4.9 billion doses per annum. Manufacturers also worked with health authorities to establish risk management plans for robust vaccine surveillance during the pandemic. Individual producers pledged significant donations of vaccine doses and tiered-pricing approaches for developing country supply. Based on the pandemic experience, a number of improvements would strengthen future preparedness. Technical improvements to rapidly select optimal vaccine viruses, and processes to speed up vaccine standardization, could accelerate and extend vaccine availability. Establishing vaccine supply agreements beforehand would avoid the need for complex discussions during a period of intense time pressure. Enhancing

  12. Evaluation of In Vitro Cross-Reactivity to Avian H5N1 and Pandemic H1N1 2009 Influenza Following Prime Boost Regimens of Seasonal Influenza Vaccination in Healthy Human Subjects: A Randomised Trial

    DTIC Science & Technology

    2013-03-26

    virus (IIV) vaccine (dose 0.5 mL intramuscularly, purchased in Thailand from Sanofi Pasteur). Both vaccines contained the three strains for the 2009/10...H1N1 2009 Influenza Following Prime Boost Regimens of Seasonal Influenza Vaccination in Healthy Human Subjects: A Randomised Trial. 5a. CONTRACT NUMBER...reported by WHO since 2003 [1]. Current seasonal trivalent influenza vaccines rely on predicted antigens based on the previous season’s circulating

  13. An H5N1-based matrix protein 2 ectodomain tetrameric peptide vaccine provides cross-protection against lethal infection with H7N9 influenza virus.

    PubMed

    Leung, Ho-Chuen; Chan, Chris Chung-Sing; Poon, Vincent Kwok-Man; Zhao, Han-Jun; Cheung, Chung-Yan; Ng, Fai; Huang, Jian-Dong; Zheng, Bo-Jian

    2015-04-01

    In March 2013, a patient infected with a novel avian influenza A H7N9 virus was reported in China. Since then, there have been 458 confirmed infection cases and 177 deaths. The virus contains several human-adapted markers, indicating that H7N9 has pandemic potential. The outbreak of this new influenza virus highlighted the need for the development of universal influenza vaccines. Previously, we demonstrated that a tetrameric peptide vaccine based on the matrix protein 2 ectodomain (M2e) of the H5N1 virus (H5N1-M2e) could protect mice from lethal infection with different clades of H5N1 and 2009 pandemic H1N1 influenza viruses. In this study, we investigated the cross-protection of H5N1-M2e against lethal infection with the new H7N9 virus. Although five amino acid differences existed at positions 13, 14, 18, 20, and 21 between M2e of H5N1 and H7N9, H5N1-M2e vaccination with either Freund's adjuvant or the Sigma adjuvant system (SAS) induced a high level of anti-M2e antibody, which cross-reacted with H7N9-M2e peptide. A mouse-adapted H7N9 strain, A/Anhui/01/2013m, was used for lethal challenge in animal experiments. H5N1-M2e vaccination provided potent cross-protection against lethal challenge of the H7N9 virus. Reduced viral replication and histopathological damage of mouse lungs were also observed in the vaccinated mice. Our results suggest that the tetrameric H5N1-M2e peptide vaccine could protect against different subtypes of influenza virus infections. Therefore, this vaccine may be an ideal candidate for developing a universal vaccine to prevent the reemergence of avian influenza A H7N9 virus and the emergence of potential novel reassortants of influenza virus.

  14. Immune efficacy of an adenoviral vector-based swine influenza vaccine against antigenically distinct H1N1 strains in mice.

    PubMed

    Wu, Yunpu; Yang, Dawei; Xu, Bangfeng; Liang, Wenhua; Sui, Jinyu; Chen, Yan; Yang, Huanliang; Chen, Hualan; Wei, Ping; Qiao, Chuanling

    2017-11-01

    Avian-like H1N1 swine influenza viruses are prevalent in pigs and have occasionally crossed the species barrier and infected humans, which highlights the importance of preventing swine influenza. Human adenovirus serotype 5 (Ad5) has been tested in human influenza vaccine clinical trials and has exhibited a reliable safety profile. Here, we generated a replication-defective, recombinant adenovirus (designated as rAd5-avH1HA) expressing the hemagglutinin gene of an avian-like H1N1 virus (A/swine/Zhejiang/199/2013, ZJ/199/13). Using a BALB/c mouse model, we showed that a two-dose intramuscular administration of recombinant rAd5-avH1HA induced high levels of hemagglutination inhibition antibodies and prevented homologous and heterologous H1N1 virus-induced weight loss, as well as viral replication in the nasal turbinates and lungs of mice. Furthermore, a prime-boost immunization strategy trial with a recombinant plasmid (designated as pCAGGS-HA) followed by rAd5-avH1HA vaccine provided effective protection against homologous and heterologous H1N1 virus infection in mice. These results indicate that rAd5-avH1HA is an efficacious genetically engineered vaccine candidate against H1N1 swine influenza. Future studies should examine its immune efficacy in pigs. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Genome-Wide Analysis of Evolutionary Markers of Human Influenza A(H1N1)pdm09 and A(H3N2) Viruses May Guide Selection of Vaccine Strain Candidates.

    PubMed

    Belanov, Sergei S; Bychkov, Dmitrii; Benner, Christian; Ripatti, Samuli; Ojala, Teija; Kankainen, Matti; Kai Lee, Hong; Wei-Tze Tang, Julian; Kainov, Denis E

    2015-11-27

    Here we analyzed whole-genome sequences of 3,969 influenza A(H1N1)pdm09 and 4,774 A(H3N2) strains that circulated during 2009-2015 in the world. The analysis revealed changes at 481 and 533 amino acid sites in proteins of influenza A(H1N1)pdm09 and A(H3N2) strains, respectively. Many of these changes were introduced as a result of random drift. However, there were 61 and 68 changes that were present in relatively large number of A(H1N1)pdm09 and A(H3N2) strains, respectively, that circulated during relatively long time. We named these amino acid substitutions evolutionary markers, as they seemed to contain valuable information regarding the viral evolution. Interestingly, influenza A(H1N1)pdm09 and A(H3N2) viruses acquired non-overlapping sets of evolutionary markers. We next analyzed these characteristic markers in vaccine strains recommended by the World Health Organization for the past five years. Our analysis revealed that vaccine strains carried only few evolutionary markers at antigenic sites of viral hemagglutinin (HA) and neuraminidase (NA). The absence of these markers at antigenic sites could affect the recognition of HA and NA by human antibodies generated in response to vaccinations. This could, in part, explain moderate efficacy of influenza vaccines during 2009-2014. Finally, we identified influenza A(H1N1)pdm09 and A(H3N2) strains, which contain all the evolutionary markers of influenza A strains circulated in 2015, and which could be used as vaccine candidates for the 2015/2016 season. Thus, genome-wide analysis of evolutionary markers of influenza A(H1N1)pdm09 and A(H3N2) viruses may guide selection of vaccine strain candidates. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  16. Pandemic influenza H1N1 2009 infection in Victoria, Australia: no evidence for harm or benefit following receipt of seasonal influenza vaccine in 2009.

    PubMed

    Kelly, Heath A; Grant, Kristina A; Fielding, James E; Carville, Kylie S; Looker, Clare O; Tran, Thomas; Jacoby, Peter

    2011-08-26

    Conflicting findings regarding the level of protection offered by seasonal influenza vaccination against pandemic influenza H1N1 have been reported. We performed a test-negative case control study using sentinel patients from general practices in Victoria to estimate seasonal influenza vaccine effectiveness against laboratory proven infection with pandemic influenza. Cases were defined as patients with an influenza-like illness who tested positive for influenza while controls had an influenza-like illness but tested negative. We found no evidence of significant protection from seasonal vaccine against pandemic influenza virus infection in any age group. Age-stratified point estimates, adjusted for pandemic phase, ranged from 44% in persons aged less than 5 years to -103% (odds ratio=2.03) in persons aged 50-64 years. Vaccine effectiveness, adjusted for age group and pandemic phase, was 3% (95% CI -48 to 37) for all patients. Our study confirms the results from our previous interim report, and other studies, that failed to demonstrate benefit or harm from receipt of seasonal influenza vaccine in patients with confirmed infection with pandemic influenza H1N1 2009. Copyright © 2011 Elsevier Ltd. All rights reserved.

  17. Safety and Immune Responses in Children After Concurrent or Sequential 2009 H1N1 and 2009–2010 Seasonal Trivalent Influenza Vaccinations

    PubMed Central

    Frey, Sharon E.; Bernstein, David I.; Gerber, Michael A.; Keyserling, Harry L.; Munoz, Flor M.; Winokur, Patricia L.; Turley, Christine B.; Rupp, Richard E.; Hill, Heather; Wolff, Mark; Noah, Diana L.; Ross, Allison C.; Cress, Gretchen; Belshe, Robert B.

    2012-01-01

    Background. Administering 2 separate vaccines for seasonal and pandemic influenza was necessary in 2009. Therefore, we conducted a randomized trial of monovalent 2009 H1N1 influenza vaccine (2009 H1N1 vaccine) and seasonal trivalent inactivated influenza vaccine (TIV; split virion) given sequentially or concurrently in previously vaccinated children. Methods. Children randomized to 4 study groups and stratified by age received 1 dose of seasonal TIV and 2 doses of 2009 H1N1 vaccine in 1 of 4 combinations. Injections were given at 21-day intervals and serum samples for hemagglutination inhibition antibody responses were obtained prior to and 21 days after each vaccination. Reactogenicity and adverse events were monitored. Results. All combinations of vaccines were safe in the 531 children enrolled. Generally, 1 dose of 2009 H1N1 vaccine and 1 dose of TIV, regardless of sequence or concurrency of administration, was immunogenic in children ≥10 years of age; children <10 years of age required 2 doses of 2009 H1N1 vaccine. Conclusions. Vaccines were generally well tolerated. The immune responses to 2009 H1N1 vaccine were adequate regardless of the sequence of vaccination in all age groups but the sequence affected titers to TIV antigens. Two doses of 2009 H1N1 vaccine were required to achieve a protective immune response in children <10 years of age. Clinical Trials Registration. NCT00943202. PMID:22802432

  18. Cold-Adapted Influenza and Recombinant Adenovirus Vaccines Induce Cross-Protective Immunity against pH1N1 Challenge in Mice

    PubMed Central

    Soboleski, Mark R.; Gabbard, Jon D.; Price, Graeme E.; Misplon, Julia A.; Lo, Chia-Yun; Perez, Daniel R.; Ye, Jianqiang; Tompkins, S. Mark; Epstein, Suzanne L.

    2011-01-01

    Background The rapid spread of the 2009 H1N1 pandemic influenza virus (pH1N1) highlighted problems associated with relying on strain-matched vaccines. A lengthy process of strain identification, manufacture, and testing is required for current strain-matched vaccines and delays vaccine availability. Vaccines inducing immunity to conserved viral proteins could be manufactured and tested in advance and provide cross-protection against novel influenza viruses until strain-matched vaccines became available. Here we test two prototype vaccines for cross-protection against the recent pandemic virus. Methodology/Principal Findings BALB/c and C57BL/6 mice were intranasally immunized with a single dose of cold-adapted (ca) influenza viruses from 1977 or recombinant adenoviruses (rAd) expressing 1934 nucleoprotein (NP) and consensus matrix 2 (M2) (NP+M2-rAd). Antibodies against the M2 ectodomain (M2e) were seen in NP+M2-rAd immunized BALB/c but not C57BL/6 mice, and cross-reacted with pH1N1 M2e. The ca-immunized mice did not develop antibodies against M2e. Despite sequence differences between vaccine and challenge virus NP and M2e epitopes, extensive cross-reactivity of lung T cells with pH1N1 peptides was detected following immunization. Both ca and NP+M2-rAd immunization protected BALB/c and C57BL/6 mice against challenge with a mouse-adapted pH1N1 virus. Conclusion/Significance Cross-protective vaccines such as NP+M2-rAd and ca virus are effective against pH1N1 challenge within 3 weeks of immunization. Protection was not dependent on recognition of the highly variable external viral proteins and could be achieved with a single vaccine dose. The rAd vaccine was superior to the ca vaccine by certain measures, justifying continued investigation of this experimental vaccine even though ca vaccine is already available. This study highlights the potential for cross-protective vaccines as a public health option early in an influenza pandemic. PMID:21789196

  19. Live, Attenuated Influenza A H5N1 Candidate Vaccines Provide Broad Cross-Protection in Mice and Ferrets

    PubMed Central

    Mills, Kimberly L; Jin, Hong; Duke, Greg; Lu, Bin; Luke, Catherine J; Murphy, Brian; Swayne, David E; Kemble, George; Subbarao, Kanta

    2006-01-01

    Background Recent outbreaks of highly pathogenic influenza A H5N1 viruses in humans and avian species that began in Asia and have spread to other continents underscore an urgent need to develop vaccines that would protect the human population in the event of a pandemic. Methods and Findings Live, attenuated candidate vaccines possessing genes encoding a modified H5 hemagglutinin (HA) and a wild-type (wt) N1 neuraminidase from influenza A H5N1 viruses isolated in Hong Kong and Vietnam in 1997, 2003, and 2004, and remaining gene segments derived from the cold-adapted (ca) influenza A vaccine donor strain, influenza A/Ann Arbor/6/60 ca (H2N2), were generated by reverse genetics. The H5N1 ca vaccine viruses required trypsin for efficient growth in vitro, as predicted by the modification engineered in the gene encoding the HA, and possessed the temperature-sensitive and attenuation phenotypes specified by the internal protein genes of the ca vaccine donor strain. More importantly, the candidate vaccines were immunogenic in mice. Four weeks after receiving a single dose of 106 50% tissue culture infectious doses of intranasally administered vaccines, mice were fully protected from lethality following challenge with homologous and antigenically distinct heterologous wt H5N1 viruses from different genetic sublineages (clades 1, 2, and 3) that were isolated in Asia between 1997 and 2005. Four weeks after receiving two doses of the vaccines, mice and ferrets were fully protected against pulmonary replication of homologous and heterologous wt H5N1 viruses. Conclusions The promising findings in these preclinical studies of safety, immunogenicity, and efficacy of the H5N1 ca vaccines against antigenically diverse H5N1 vaccines provide support for their careful evaluation in Phase 1 clinical trials in humans. PMID:16968127

  20. Fully human broadly neutralizing monoclonal antibodies against influenza A viruses generated from the memory B cells of a 2009 pandemic H1N1 influenza vaccine recipient

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hu, Weibin; Chen, Aizhong; Miao, Yi

    Whether the 2009 pandemic H1N1 influenza vaccine can induce heterosubtypic cross-protective anti-hemagglutinin (HA) neutralizing antibodies is an important issue. We obtained a panel of fully human monoclonal antibodies from the memory B cells of a 2009 pandemic H1N1 influenza vaccine recipient. Most of the monoclonal antibodies targeted the HA protein but not the HA1 fragment. Among the analyzed antibodies, seven mAbs exhibited neutralizing activity against several influenza A viruses of different subtypes. The conserved linear epitope targeted by the neutralizing mAbs (FIEGGWTGMVDGWYGYHH) is part of the fusion peptide on HA2. Our work suggests that a heterosubtypic neutralizing antibody response primarilymore » targeting the HA stem region exists in recipients of the 2009 pandemic H1N1 influenza vaccine. The HA stem region contains various conserved neutralizing epitopes with the fusion peptide as an important one. This work may aid in the design of a universal influenza A virus vaccine.« less

  1. Clinical and Immune Responses to Inactivated Influenza A(H1N1)pdm09 Vaccine in Children

    PubMed Central

    Kotloff, Karen L.; Halasa, Natasha B.; Harrison, Christopher J.; Englund, Janet A.; Walter, Emmanuel B.; King, James C.; Creech, C. Buddy; Healy, Sara A.; Dolor, Rowena J.; Stephens, Ina; Edwards, Kathryn M.; Noah, Diana L.; Hill, Heather; Wolff, Mark

    2014-01-01

    Background As the influenza AH1N1 pandemic emerged in 2009, children were found to experience high morbidity and mortality and were prioritized for vaccination. This multicenter, randomized, double-blind, age-stratified trial assessed the safety and immunogenicity of inactivated influenza A(H1N1)pdm09 vaccine in healthy children aged 6 months to 17 years. Methods Children received two doses of approximately 15 μg or 30 μg hemagglutin antigen 21 days apart. Reactogenicity was assessed for 8 days after each dose, adverse events through day 42, and serious adverse events or new-onset chronic illnesses through day 201. Serum hemagglutination inhibition (HAI) titers were measured on days 0 (pre-vaccination), 8, 21, 29, and 42. Results A total of 583 children received the first dose and 571 received the second dose of vaccine. Vaccinations were generally well-tolerated and no related serious adverse events were observed. The 15 μg dosage elicited a seroprotective HAI (≥1:40) in 20%, 47%, and 93% of children in the 6-35 month, 3-9 year, and 10-17 year age strata 21 days after dose 1 and in 78%, 82%, and 98% of children 21 days after dose 2, respectively. The 30 μg vaccine dosage induced similar responses. Conclusions The inactivated influenza A(H1N1)pdm09 vaccine exhibited a favorable safety profile at both dosage levels. While a single 15 or 30 μg dose induced seroprotective antibody responses in most 10-17 year olds, younger children required 2 doses, even when receiving dosages 4-6 fold higher than recommended. Well-tolerated vaccines are needed that induce immunity after a single dose for use in young children during influenza pandemics. PMID:25222307

  2. Antibody Persistence in Adults Two Years after Vaccination with an H1N1 2009 Pandemic Influenza Virus-Like Particle Vaccine

    PubMed Central

    Villasís-Keever, Miguel Ángel; Núñez-Valencia, Adriana; Boscó-Gárate, Ilka; Lozano-Dubernard, Bernardo; Lara-Puente, Horacio; Espitia, Clara; Alpuche-Aranda, Celia; Bonifaz, Laura C.; Arriaga-Pizano, Lourdes; Pastelin-Palacios, Rodolfo; Isibasi, Armando; López-Macías, Constantino

    2016-01-01

    The influenza virus is a human pathogen that causes epidemics every year, as well as potential pandemic outbreaks, as occurred in 2009. Vaccination has proven to be sufficient in the prevention and containment of viral spreading. In addition to the current egg-based vaccines, new and promising vaccine platforms, such as cell culture-derived vaccines that include virus-like particles (VLPs), have been developed. VLPs have been shown to be both safe and immunogenic against influenza infections. Although antibody persistence has been studied in traditional egg-based influenza vaccines, studies on antibody response durations induced by VLP influenza vaccines in humans are scarce. Here, we show that subjects vaccinated with an insect cell-derived VLP vaccine, in the midst of the 2009 H1N1 influenza pandemic outbreak in Mexico City, showed antibody persistence up to 24 months post-vaccination. Additionally, we found that subjects that reported being revaccinated with a subsequent inactivated influenza virus vaccine showed higher antibody titres to the pandemic influenza virus than those who were not revaccinated. These findings provide insights into the duration of the antibody responses elicited by an insect cell-derived pandemic influenza VLP vaccine and the possible effects of subsequent influenza vaccination on antibody persistence induced by this VLP vaccine in humans. PMID:26919288

  3. Enhanced pneumonia and disease in pigs vaccinated with an inactivated human-like (δ-cluster) H1N2 vaccine and challenged with pandemic 2009 H1N1 influenza virus.

    PubMed

    Gauger, Phillip C; Vincent, Amy L; Loving, Crystal L; Lager, Kelly M; Janke, Bruce H; Kehrli, Marcus E; Roth, James A

    2011-03-24

    Influenza is an economically important respiratory disease affecting swine world-wide with potential zoonotic implications. Genetic reassortment and drift has resulted in genetically and antigenically distinct swine influenza viruses (SIVs). Consequently, prevention of SIV infection is challenging due to the increased rate of genetic change and a potential lack of cross-protection between vaccine strains and circulating novel isolates. This report describes a vaccine-heterologous challenge model in which pigs were administered an inactivated H1N2 vaccine with a human-like (δ-cluster) H1 six and three weeks before challenge with H1 homosubtypic, heterologous 2009 pandemic H1N1. At necropsy, macroscopic and microscopic pneumonia scores were significantly higher in the vaccinated and challenged (Vx/Ch) group compared to non-vaccinated and challenged (NVx/Ch) pigs. The Vx/Ch group also demonstrated enhanced clinical disease and a significantly elevated pro-inflammatory cytokine profile in bronchoalveolar lavage fluid compared to the NVx/Ch group. In contrast, viral shedding and replication were significantly higher in NVx/Ch pigs although all challenged pigs, including Vx/Ch pigs, were shedding virus in nasal secretions. Hemagglutination inhibition (HI) and serum neutralizing (SN) antibodies were detected to the priming antigen in the Vx/Ch pigs but no measurable cross-reacting HI or SN antibodies were detected to pandemic H1N1 (pH1N1). Overall, these results suggest that inactivated SIV vaccines may potentiate clinical signs, inflammation and pneumonia following challenge with divergent homosubtypic viruses that do not share cross-reacting HI or SN antibodies. Published by Elsevier Ltd.

  4. Aerosol Delivery of a Candidate Universal Influenza Vaccine Reduces Viral Load in Pigs Challenged with Pandemic H1N1 Virus

    PubMed Central

    Morgan, Sophie B.; Hemmink, Johanneke D.; Porter, Emily; Harley, Ross; Shelton, Holly; Aramouni, Mario; Everett, Helen E.; Brookes, Sharon M.; Bailey, Michael; Townsend, Alain M.; Charleston, Bryan

    2016-01-01

    Influenza A viruses are a major health threat to livestock and humans, causing considerable mortality, morbidity, and economic loss. Current inactivated influenza vaccines are strain specific and new vaccines need to be produced at frequent intervals to combat newly arising influenza virus strains, so that a universal vaccine is highly desirable. We show that pandemic H1N1 influenza virus in which the hemagglutinin signal sequence has been suppressed (S-FLU), when administered to pigs by aerosol can induce CD4 and CD8 T cell immune responses in blood, bronchoalveolar lavage (BAL), and tracheobronchial lymph nodes. Neutralizing Ab was not produced. Detection of a BAL response correlated with a reduction in viral titer in nasal swabs and lungs, following challenge with H1N1 pandemic virus. Intratracheal immunization with a higher dose of a heterologous H5N1 S-FLU vaccine induced weaker BAL and stronger tracheobronchial lymph node responses and a lesser reduction in viral titer. We conclude that local cellular immune responses are important for protection against influenza A virus infection, that these can be most efficiently induced by aerosol immunization targeting the lower respiratory tract, and that S-FLU is a promising universal influenza vaccine candidate. PMID:27183611

  5. The Social Ecological Model as a Framework for Determinants of 2009 H1N1 Influenza Vaccine Uptake in the United States

    ERIC Educational Resources Information Center

    Kumar, Supriya; Quinn, Sandra Crouse; Kim, Kevin H.; Musa, Donald; Hilyard, Karen M.; Freimuth, Vicki S.

    2012-01-01

    Research on influenza vaccine uptake has focused largely on intrapersonal determinants (perceived risk, past vaccine acceptance, perceived vaccine safety) and on physician recommendation. The authors used a social ecological framework to examine influenza vaccine uptake during the 2009 H1N1 pandemic. Surveying an adult population (n = 2,079) in…

  6. Correlates of 2009 H1N1 Influenza Vaccine Acceptability among Parents and Their Adolescent Children

    ERIC Educational Resources Information Center

    Painter, Julia E.; Gargano, Lisa M.; Sales, Jessica M.; Morfaw, Christopher; Jones, LaDawna M.; Murray, Dennis; DiClemente, Ralph J.; Hughes, James M.

    2011-01-01

    School-aged children were a priority group for receipt of the pandemic (2009) H1N1 influenza vaccine. Both parental and adolescent attitudes likely influence vaccination behaviors. Data were collected from surveys distributed to middle- and high-school students and their parents in two counties in rural Georgia. Multivariable logistic regression…

  7. A tool for the economic analysis of mass prophylaxis operations with an application to H1N1 influenza vaccination clinics.

    PubMed

    Cho, Bo-Hyun; Hicks, Katherine A; Honeycutt, Amanda A; Hupert, Nathaniel; Khavjou, Olga; Messonnier, Mark; Washington, Michael L

    2011-01-01

    This article uses the 2009 H1N1 influenza vaccination program experience to introduce a cost analysis approach that may be relevant for planning mass prophylaxis operations, such as vaccination clinics at public health centers, work sites, schools, or pharmacy-based clinics. These costs are important for planning mass influenza vaccination activities and are relevant for all public health emergency preparedness scenarios requiring countermeasure dispensing. We demonstrate how costs vary depending on accounting perspective, staffing composition, and other factors. We also describe a mass vaccination clinic budgeting tool that clinic managers may use to estimate clinic costs and to examine how costs vary depending on the availability of volunteers or donated supplies and on the number of patients vaccinated per hour. Results from pilot tests with school-based H1N1 influenza vaccination clinic managers are described. The tool can also contribute to planning efforts for universal seasonal influenza vaccination.

  8. Incidence of narcolepsy after H1N1 influenza and vaccinations: Systematic review and meta-analysis.

    PubMed

    Sarkanen, Tomi O; Alakuijala, Anniina P E; Dauvilliers, Yves A; Partinen, Markku M

    2018-04-01

    An increased incidence of narcolepsy was seen in many countries after the pandemic H1N1 influenza vaccination campaign in 2009-2010. The H1N1 vaccine - narcolepsy connection is based on observational studies that are prone to various biases, e.g., confounding by H1N1 infection, and ascertainment, recall and selection biases. A direct pathogenic link has, however, remained elusive. We conducted a systematic review and meta-analysis to analyze the magnitude of H1N1 vaccination related risk and to examine if there was any association with H1N1 infection itself. We searched all articles from PubMed, Web of Science and Scopus, and other relevant sources reporting the incidence and risk of post-vaccine narcolepsy. In our paper, we show that the risk appears to be limited to only one vaccine (Pandemrix ® ). During the first year after vaccination, the relative risk of narcolepsy was increased 5 to 14-fold in children and adolescents and 2 to 7-fold in adults. The vaccine attributable risk in children and adolescents was around 1 per 18,400 vaccine doses. Studies from Finland and Sweden also appear to demonstrate an extended risk of narcolepsy into the second year following vaccination, but such conclusions should be interpreted with a word of caution due to possible biases. Benefits of immunization outweigh the risk of vaccination-associated narcolepsy, which remains a rare disease. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Epidemiology of pandemic influenza A/H1N1 virus during 2009-2010 in Taiwan.

    PubMed

    Lan, Yu-Ching; Su, Mei-Chi; Chen, Chao-Hsien; Huang, Su-Hua; Chen, Wan-Li; Tien, Ni; Lin, Cheng-Wen

    2013-10-01

    Outbreak of swine-origin influenza A/H1N1 virus (pdmH1N1) occurred in 2009. Taiwanese authorities implemented nationwide vaccinations with pdmH1N1-specific inactivated vaccine as of November 2009. This study evaluates prevalence, HA phylogenetic relationship, and transmission dynamic of influenza A and B viruses in Taiwan in 2009-2010. Respiratory tract specimens were analyzed for influenza A and B viruses. The pdmH1N1 peaked in November 2009, was predominant from August 2009 to January 2010, then sharply dropped in February 2010. Significant prevalence peaks of influenza B in April-June of 2010 and H3N2 virus in July and August were observed. Highest percentage of pdmH1N1- and H3N2-positive cases appeared among 11-15-year-olds; influenza B-positive cases were dominant among those 6-10 years old. Maximum likelihood phylogenetic trees showed 11 unique clusters of pdmH1N1, seasonal H3N2 influenza A and B viruses, as well as transmission clusters and mixed infections of influenza strains in Taiwan. The 2009 pdmH1N1 virus was predominant in Taiwan from August 2009 to January 2010; seasonal H3N2 influenza A and B viruses exhibited small prevalence peaks after nationwide vaccinations. Phylogenetic evidence indicated transmission clusters and multiple independent clades of co-circulating influenza A and B strains in Taiwan. Copyright © 2013 The Authors. Published by Elsevier B.V. All rights reserved.

  10. Guillain-Barré Syndrome During the 2009–2010 H1N1 Influenza Vaccination Campaign: Population-based Surveillance Among 45 Million Americans

    PubMed Central

    Wise, Matthew E.; Viray, Melissa; Sejvar, James J.; Lewis, Paige; Baughman, Andrew L.; Connor, Walter; Danila, Richard; Giambrone, Greg P.; Hale, Christa; Hogan, Brenna C.; Meek, James I.; Murphree, Rendi; Oh, John Y.; Reingold, Arthur; Tellman, Norisse; Conner, Susan M.; Singleton, James A.; Lu, Peng-Jun; DeStefano, Frank; Fridkin, Scott K.; Vellozzi, Claudia; Morgan, Oliver W.

    2012-01-01

    Because of widespread distribution of the influenza A (H1N1) 2009 monovalent vaccine (pH1N1 vaccine) and the prior association between Guillain-Barré syndrome (GBS) and the 1976 H1N1 influenza vaccine, enhanced surveillance was implemented to estimate the magnitude of any increased GBS risk following administration of pH1N1 vaccine. The authors conducted active, population-based surveillance for incident cases of GBS among 45 million persons residing at 10 Emerging Infections Program sites during October 2009–May 2010; GBS was defined according to published criteria. The authors determined medical and vaccine history for GBS cases through medical record review and patient interviews. The authors used vaccine coverage data to estimate person-time exposed and unexposed to pH1N1 vaccine and calculated age- and sex-adjusted rate ratios comparing GBS incidence in these groups, as well as age- and sex-adjusted numbers of excess GBS cases. The authors received 411 reports of confirmed or probable GBS. The rate of GBS immediately following pH1N1 vaccination was 57% higher than in person-time unexposed to vaccine (adjusted rate ratio = 1.57, 95% confidence interval: 1.02, 2.21), corresponding to 0.74 excess GBS cases per million pH1N1 vaccine doses (95% confidence interval: 0.04, 1.56). This excess risk was much smaller than that observed during the 1976 vaccine campaign and was comparable to some previous seasonal influenza vaccine risk assessments. PMID:22582209

  11. Responses to pandemic ASO3-adjuvanted A/California/07/09 H1N1 influenza vaccine in human immunodeficiency virus-infected individuals.

    PubMed

    Kelly, Deborah; Burt, Kimberley; Missaghi, Bayan; Barrett, Lisa; Keynan, Yoav; Fowke, Keith; Grant, Michael

    2012-08-31

    Influenza infection may be more serious in human immunodeficiency virus (HIV)-infected individuals, therefore, vaccination against seasonal and pandemic strains is highly advised. Seasonal influenza vaccines have had no significant negative effects in well controlled HIV infection, but the impact of adjuvanted pandemic A/California/07/2009 H1N1 influenza hemaglutinin (HA) vaccine, which was used for the first time in the Canadian population as an authorized vaccine in autumn 2009, has not been extensively studied. Assess vaccine-related effects on CD4(+) T cell counts and humoral responses to the vaccine in individuals attending the Newfoundland and Labrador Provincial HIV clinic. A single dose of Arepanrix™ split vaccine including 3.75 μg A/California/07/2009 H1N1 HA antigen and ASO3 adjuvant was administered to 81 HIV-infected individuals by intramuscular injection. Plasma samples from shortly before, and 1-5 months after vaccination were collected from 80/81 individuals to assess humoral anti-H1N1 HA responses using a sensitive microbead-based array assay. Data on CD4(+) T cell counts, plasma viral load, antiretroviral therapy and patient age were collected from clinical records of 81 individuals. Overall, 36/80 responded to vaccination either by seroconversion to H1N1 HA or with a clear increase in anti-H1N1 HA antibody levels. Approximately 1/3 (28/80) had pre-existing anti-H1N1 HA antibodies and were more likely to respond to vaccination (22/28). Responders had higher baseline CD4(+) T cell counts and responders without pre-existing antibodies against H1N1 HA were younger than either non-responders or responders with pre-existing antibodies. Compared to changes in their CD4(+) T cell counts observed over a similar time period one year later, vaccine recipients displayed a minor, transient fall in CD4(+) T cell numbers, which was greater amongst responders. We observed low response rates to the 2009 pandemic influenza vaccine among HIV-infected individuals

  12. Immune response to pandemic H1N1 2009 influenza a vaccination in pediatric liver transplant recipients.

    PubMed

    Haller, Wolfram; Buttery, Jim; Laurie, Karen; Beyerle, Kathe; Hardikar, Winita; Alex, George

    2011-08-01

    After the announcement of a worldwide pandemic in June 2009, a single dose of a monovalent pandemic H1N1 2009 influenza A (pH1N1/09) vaccine was advocated for all Australians who were 10 years and older because of excellent immunogenicity trial results for healthy children and adults. Immunocompromised patients have previously been shown to have lower seroconversion rates after routine vaccinations. There is a lack of data concerning the immune response of this patient group after pH1N1/09 vaccination. The aim of this study was to assess the immunogenicity of a pH1N1/09 vaccine in pediatric liver transplant recipients 10 years of age or older. Liver transplant recipients ≥ 10 years were prospectively recruited. All participants were administered a single intramuscular injection of the pH1N1/09 vaccine (15 μg). Serum antibody levels were determined by hemagglutination immediately before and ≥ 6 weeks after vaccination. Clinical and laboratory data (age, time since transplantation, immunosuppression, and lymphocyte counts) were analyzed comparing seroconverters and nonconverters with the Student's t test. A second dose of the vaccine was offered to all those who displayed no seroprotective titers after the first vaccination. Antibody levels were again determined 6 weeks later. Twenty-one of 28 liver transplant patients completed the study. The seroconversion rate was 62% after the first dose and 89.5% after the second dose. At baseline, 7 of 21 patients (33.4%) were already seropositive. Increasing time since transplantation positively correlated with successful seroconversion. In conclusion, a single dose of a pandemic influenza A vaccine does not elicit a reliable immune response in adolescent pediatric liver transplant patients. A second dose of the vaccine is warranted in this group of patients, at least in a pandemic scenario. There is an urgent need to further assess vaccine strategies in this high-risk group. Copyright © 2011 American Association for the

  13. Assessment of efficacy and safety of pandemic A/H1N1/2009 influenza vaccine in a group of health care workers.

    PubMed

    Mascagni, P; Vicenzi, Elisa; Kajaste-Rudnitski, Anna; Pellicciotta, G; Monti, A; Cervi, Carla; Vitalucci, Roberta; Toffoletto, F

    2012-01-01

    The development in an extremely short time of an efficacious and safe vaccine against the pandemi A/H1N1 virus was a challenge that involved the entire scientific community. To assess the immunological and clinical efficacy of the new H1N1v monovalent influenza vaccine (Focetria Novartis Vaccines, Siena, Italy) in a group of health care workers (HCWs). A total of 148 volunteer HCWs were enrolled between Mid-Novembre 2009 and December 2009. After measuring antibody titers, a single intramuscular dose of 7.5 microg of Focetria monovalent vaccine against A/H1N1/2009 influenza virus with MF59C.1 adjuvant was administered. Antibody titers (median value) before and after a single dose of vaccine, measured by means of standard beam-agglutination inhibition test (HAI), increased from 32 to 256 (p < 0.001). After vaccination, 79.7% of the subjects showed antibody seroconversion, and in 97.3% seroprotection was achieved. The ratio between the geometric means of antibody titers (GMTR) was 6.69. For the 3 subjects who reported symptoms of ILI (Influenza-like illness), a regular nasal-pharyngeal swab sample was taken to identify the virus type by RT-PCR, the laboratory results of tests performed on these samples were negative for pandemic A/H1N1/2009 virus. During the entire follow-up period of 6 months no severe adverse events occurred. The vaccine against pandemic A/H1N1/2009 virus provided protection against the virus and not only contributed to a significant immunization (according to EMEA criteria), but kept all 148 subjects under study free from A/H1N1/2009 influenza illness.

  14. Efficacy of an AS03A-adjuvanted split H5N1 influenza vaccine against an antigenically distinct low pathogenic H5N1 virus in pigs.

    PubMed

    De Vleeschauwer, Annebel R; Baras, Benoît; Kyriakis, Constantinos S; Jacob, Valérie; Planty, Camille; Giannini, Sandra L; Mossman, Sally; Van Reeth, Kristien

    2012-08-10

    We used the pig model of influenza to examine the efficacy of an AS03(A)-adjuvanted split H5N1 (A/Indonesia/05/2005) vaccine against challenge with a low pathogenic (LP) H5N1 avian influenza (AI) virus (duck/Minnesota/1525/1981) with only 85% amino acid homology in its HA1. Influenza seronegative pigs were vaccinated twice intramuscularly with adjuvanted vaccine at 3 antigen doses, unadjuvanted vaccine or placebo. All pigs were challenged 4 weeks after the second vaccination and euthanized 2 days later. After 2 vaccinations, all pigs in the adjuvanted vaccine groups had high hemagglutination inhibiting (HI) antibody titers to the vaccine strain (160-640), and lower antibody titers to the A/Vietnam/1194/04 H5N1 strain and to 2 LP H5 viruses with 90-91% amino acid homology to the vaccine strain (20-160). Eight out of 12 pigs had HI titers (10-20) to the challenge virus immediately before challenge. Neuraminidase inhibiting antibodies to the challenge virus were detected in most pigs (7/12) and virus neutralizing antibodies in all pigs. There was no antigen-dose dependent effect on the antibody response among the pigs immunized with adjuvanted H5N1 vaccines. After challenge, these pigs showed a complete clinical protection, reduced lung lesions and a significant protection against virus replication in the respiratory tract. Though the challenge virus showed only moderate replication efficiency in pigs, our study suggests that AS03(A)-adjuvanted H5N1 vaccine may confer a broader protection than generally assumed. The pros and cons of the pig as an H5N1 challenge model are also discussed. Copyright © 2012 Elsevier Ltd. All rights reserved.

  15. Cost-Effectiveness of 2009 Pandemic Influenza A(H1N1) Vaccination in the United States

    PubMed Central

    Prosser, Lisa A.; Lavelle, Tara A.; Fiore, Anthony E.; Bridges, Carolyn B.; Reed, Carrie; Jain, Seema; Dunham, Kelly M.; Meltzer, Martin I.

    2011-01-01

    Background Pandemic influenza A(H1N1) (pH1N1) was first identified in North America in April 2009. Vaccination against pH1N1 commenced in the U.S. in October 2009 and continued through January 2010. The objective of this study was to evaluate the cost-effectiveness of pH1N1 vaccination. Methodology A computer simulation model was developed to predict costs and health outcomes for a pH1N1 vaccination program using inactivated vaccine compared to no vaccination. Probabilities, costs and quality-of-life weights were derived from emerging primary data on pH1N1 infections in the US, published and unpublished data for seasonal and pH1N1 illnesses, supplemented by expert opinion. The modeled target population included hypothetical cohorts of persons aged 6 months and older stratified by age and risk. The analysis used a one-year time horizon for most endpoints but also includes longer-term costs and consequences of long-term sequelae deaths. A societal perspective was used. Indirect effects (i.e., herd effects) were not included in the primary analysis. The main endpoint was the incremental cost-effectiveness ratio in dollars per quality-adjusted life year (QALY) gained. Sensitivity analyses were conducted. Results For vaccination initiated prior to the outbreak, pH1N1 vaccination was cost-saving for persons 6 months to 64 years under many assumptions. For those without high risk conditions, incremental cost-effectiveness ratios ranged from $8,000–$52,000/QALY depending on age and risk status. Results were sensitive to the number of vaccine doses needed, costs of vaccination, illness rates, and timing of vaccine delivery. Conclusions Vaccination for pH1N1 for children and working-age adults is cost-effective compared to other preventive health interventions under a wide range of scenarios. The economic evidence was consistent with target recommendations that were in place for pH1N1 vaccination. We also found that the delays in vaccine availability had a substantial

  16. No effect of 2008/09 seasonal influenza vaccination on the risk of pandemic H1N1 2009 influenza infection in England.

    PubMed

    Pebody, Richard; Andrews, Nick; Waight, Pauline; Malkani, Rashmi; McCartney, Christine; Ellis, Joanna; Miller, Elizabeth

    2011-03-21

    This study reports effectiveness of trivalent influenza vaccine (TIV) against confirmed pandemic influenza infection in England using a retrospective test-negative case-control study. Cases and controls were frequency matched by age, swabbing-week and region. On univariable and multivariable analysis adjusted for underlying clinical risk factors, cases were no more or less likely than controls to be vaccinated with 2008-09 or 2007-08 season TIV. Adjusted vaccine effectiveness for the former was -6% (-43% to 22%). Vaccine effectiveness did not differ significantly by age-group or hospitalisation status. There was no evidence prior vaccination with TIV significantly altered subsequent risk of pandemic influenza H1N1 2009 infection. Copyright © 2011 Elsevier Ltd. All rights reserved.

  17. Antibody response after a single dose of an AS03-adjuvanted split-virion influenza A (H1N1) vaccine in heart transplant recipients.

    PubMed

    Meyer, Sven; Adam, Matti; Schweiger, Brunhilde; Ilchmann, Corina; Eulenburg, Christine; Sattinger, Edgar; Runte, Hendrik; Schlüter, Michael; Deuse, Tobias; Reichenspurner, Hermann; Costard-Jäckle, Angelika

    2011-05-15

    Influenza A (H1N1) has emerged as a considerable threat for recipients of organ transplants. Vaccination against the novel influenza A (H1N1) virus has generally been advocated. There is limited experience with AS03-adjuvanted A/H1N1 pandemic influenza vaccines in immunosuppressed patients. We conducted an observational, nonrandomized single-center study to assess antibody response and vaccine-related adverse effects in 47 heart transplant recipients (44 men; age, 56±13 years). The AS03-adjuvanted, inactivated split-virion A/California/7/2009 H1N1v pandemic vaccine was administered. Antibody titers were measured using hemagglutination inhibition; immunoglobulin G (IgG) response was assessed using a new pandemic influenza A IgG enzyme-linked immunosorbent assay (ELISA) test kit and compared with hemagglutination-inhibition titers. Adverse effects of vaccination were assessed by a questionnaire. Postvaccination antibody titers of greater than or equal to 1:40 were found in only 15 patients, corresponding to a seroprotection rate of 32% (95% confidence interval, 19%-47%). Sensitivity, specificity, positive predictive value, and negative predictive value of ELISA testing were 80.0%, 68.8%, 54.5%, and 88.0%, respectively. Age, time posttransplantation, and immunosuppressive regimen did not impact antibody response. Vaccination was well tolerated. Single-dose administration of an AS03-adjuvanted vaccine against the novel influenza A (H1N1) virus did not elicit seroprotective antibody concentrations in a substantial proportion of heart transplant recipients; the new pandemic influenza A IgG ELISA test kit proved to be of limited clinical use.

  18. Absence of cross‐reactive antibodies to influenza A (H1N1) 2009 before and after vaccination with 2009 Southern Hemisphere seasonal trivalent influenza vaccine in children aged 6 months–9 years: a prospective study

    PubMed Central

    McVernon, Jodie; Laurie, Karen; Barr, Ian; Kelso, Anne; Skeljo, Maryanne; Nolan, Terry

    2010-01-01

    Please cite this paper as: McVernon et al. (2010) Absence of cross‐reactive antibodies to influenza A (H1N1) 2009 before and after vaccination with 2009 Southern Hemisphere seasonal trivalent influenza vaccine in children aged 6 months–9 years: a prospective study. Influenza and Other Respiratory Viruses 5(1), 7–11. Background  Early outbreaks of the pandemic influenza A (H1N1) 2009 virus predominantly involved young children, who fuelled transmission through spread in homes and schools. Seroprevalence studies conducted on stored serum collections indicated low levels of antibody to the novel strain in this age group, leading many to recommend priority immunisation of paediatric populations. Objectives  In a prospective study, we sought evidence of cross‐reactive antibodies to the pandemic virus in children who were naïve to seasonal influenza vaccines, at baseline and following two doses of the 2009 Southern Hemisphere trivalent influenza vaccine (TIV). Patients/Methods  Twenty children were recruited, with a median age of 4 years (interquartile range 3–5 years); all received two age appropriate doses of TIV. Paired sera were collected pre‐ and post‐vaccination for the assessment of vaccine immunogenicity, using haemagglutination inhibition and microneutralisation assays against vaccine‐related viruses and influenza A (H1N1) 2009. Results  Robust responses to H3N2 were observed regardless of age or pre‐vaccination titre, with 100% seroconversion. Fewer seroconverted to the seasonal H1N1 component. Only two children were weakly seropositive (HI titre 40) to the pandemic H1N1 strain at study entry, and none showed evidence of seroconversion by HI assay following TIV administration. Conclusions  Administration of 2009 Southern Hemisphere TIV did little to elicit cross‐reactive antibodies to the pandemic H1N1 virus in children, in keeping with assay results on stored sera from studies of previous seasonal vaccines. Our findings

  19. Cumulative Risk of Guillain–Barré Syndrome Among Vaccinated and Unvaccinated Populations During the 2009 H1N1 Influenza Pandemic

    PubMed Central

    Iqbal, Shahed; Stewart, Brock; Tokars, Jerome; DeStefano, Frank

    2014-01-01

    Objectives. We sought to assess risk of Guillain–Barré syndrome (GBS) among influenza A (H1N1) 2009 monovalent (pH1N1) vaccinated and unvaccinated populations at the end of the 2009 pandemic. Methods. We applied GBS surveillance data from a US population catchment area of 45 million from October 15, 2009, through May 31, 2010. GBS cases meeting Brighton Collaboration criteria were included. We calculated the incidence density ratio (IDR) among pH1N1 vaccinated and unvaccinated populations. We also estimated cumulative GBS risk using life table analysis. Additionally, we used vaccine coverage data and census population estimates to calculate denominators. Results. There were 392 GBS cases; 64 (16%) occurred after pH1N1vaccination. The vaccinated population had lower average risk (IDR = 0.83, 95% confidence interval = 0.63, 1.08) and lower cumulative risk (6.6 vs 9.2 cases per million persons, P = .012) of GBS. Conclusions. Our findings suggest that at the end of the influenza season cumulative GBS risk was less among the pH1N1vaccinated than the unvaccinated population, suggesting the benefit of vaccination as it relates to GBS. The observed potential protective effect on GBS attributed to vaccination warrants further study. PMID:24524517

  20. Profiling of humoral response to influenza A(H1N1)pdm09 infection and vaccination measured by a protein microarray in persons with and without history of seasonal vaccination.

    PubMed

    Huijskens, Elisabeth G W; Reimerink, Johan; Mulder, Paul G H; van Beek, Janko; Meijer, Adam; de Bruin, Erwin; Friesema, Ingrid; de Jong, Menno D; Rimmelzwaan, Guus F; Peeters, Marcel F; Rossen, John W A; Koopmans, Marion

    2013-01-01

    The influence of prior seasonal influenza vaccination on the antibody response produced by natural infection or vaccination is not well understood. We compared the profiles of antibody responses of 32 naturally infected subjects and 98 subjects vaccinated with a 2009 influenza A(H1N1) monovalent MF59-adjuvanted vaccine (Focetria, Novartis), with and without a history of seasonal influenza vaccination. Antibodies were measured by hemagglutination inhibition (HI) assay for influenza A(H1N1)pdm09 and by protein microarray (PA) using the HA1 subunit for seven recent and historic H1, H2 and H3 influenza viruses, and three avian influenza viruses. Serum samples for the infection group were taken at the moment of collection of the diagnostic sample, 10 days and 30 days after onset of influenza symptoms. For the vaccination group, samples were drawn at baseline, 3 weeks after the first vaccination and 5 weeks after the second vaccination. We showed that subjects with a history of seasonal vaccination generally exhibited higher baseline titers for the various HA1 antigens than subjects without a seasonal vaccination history. Infection and pandemic influenza vaccination responses in persons with a history of seasonal vaccination were skewed towards historic antigens. Seasonal vaccination is of significant influence on the antibody response to subsequent infection and vaccination, and further research is needed to understand the effect of annual vaccination on protective immunity.

  1. Immunogenicity and safety of cell-derived MF59®-adjuvanted A/H1N1 influenza vaccine for children

    PubMed Central

    Knuf, Markus; Leroux-Roels, Geert; Rümke, Hans; Rivera, Luis; Pedotti, Paola; Arora, Ashwani Kumar; Lattanzi, Maria; Kieninger, Dorothee; Cioppa, Giovanni Della

    2015-01-01

    Mass immunization of children has the potential to decrease infection rates and prevent the transmission of influenza. We evaluated the immunogenicity, safety, and tolerability of different formulations of cell-derived MF59-adjuvanted and nonadjuvanted A/H1N1 influenza vaccine in children and adolescents. This was a randomized, single-blind, multicenter study with a total of 666 healthy subjects aged 6 months–17 y in one of 3 vaccination groups, each receiving formulations containing different amounts of influenza A/H1N1 antigen with or without MF59. A booster trivalent seasonal MF59 vaccine was administered one year after primary vaccinations. Antibody titers were assessed by hemagglutination inhibition (HI) and microneutralization assays obtained on days 1, 22, 43, 366, and 387 (3 weeks post booster). Safety was monitored throughout the study. One vaccination with 3.75 μg of A/H1N1 antigen formulated with 50% MF59 (3.75_halfMF59) or 7.5 μg of A/H1N1 antigen formulated with 100% MF59 (7.5_fullMF59) induced an HI titer ≥1:40 in >70% of children in the 1–<3, 3–8, and 9–17 y cohorts; however, 2 vaccinations with nonadjuvanted 15 μg A/H1N1 antigen were needed to achieve this response in the 1–<3 and 3–8 y cohorts. Among children aged 6–11 months, 1 dose of 7.5_fullMF59 resulted in an HI titer ≥1:40 in >70% while 2 doses of 3.75_halfMF59 were required to achieve this result. All vaccines were well tolerated. Our findings support the immunogenicity and safety of the 3.75_halfMF59 (2 doses for children <12 months) and 7.5_fullMF59 vaccine formulations for use in children and adolescents aged 6 months to 17 y The use of the 3.75_halfMF59 could have the benefit of antigen and adjuvant sparing, increasing the available vaccine doses allowing vaccination of more people. PMID:25621884

  2. A/H1N1 influenza vaccination in patients with systemic lupus erythematosus: safety and immunity.

    PubMed

    Lu, Chun-Chi; Wang, Yeau-Ching; Lai, Jenn-Haung; Lee, Tony Szu-Hsien; Lin, Hui-Tsu; Chang, Deh-Ming

    2011-01-10

    To determine the safety of and immunogenicity induced by A/H1N1 influenza vaccination in patients with systemic lupus erythematosus (SLE). The study population comprised 21 SLE patients and 15 healthy control subjects who underwent split-virion, inactivated monovalent A/H1N1 vaccination between December 2009 and January 2010. Sera were obtained before, three weeks after, and six months after vaccination. SLE disease activity index (SLEDAI) scores and autoantibodies were measured at every visit in SLE patients. Haemagglutination inhibition and the serum immunoglobulin G (IgG) level were calculated using the World Health Organization (WHO) procedure to evaluate the antibody responses. We also recorded current medications and past seasonal influenza vaccinations to analyse the interactions between vaccinations and the autoimmunity of SLE patients. The mean age of the enrolled population was 34.3 years for SLE patients and 39.4 years for control subjects. The average SLEDAI score for SLE patients was 4.1 at vaccination, 4.5 at three weeks, and 4.3 at six months. The seroprotection rate at three weeks was 76.2% in SLE patients and 80.0% in healthy control subjects; by six months, the seroprotection rate was 66.7% in SLE patients and 60% in healthy control subjects. The seroconversion rate was 76.2% in SLE patients and 80% in healthy controls at three weeks; by six months, the seroconversion rate was 52.4% in SLE patients and 53.3% in healthy controls. The response in SLE patients met the criteria of the European Committee for Proprietary Medicinal Products guidelines at three weeks, while the percentage of seroprotection did not at six months. The clinical disease activity and SLEDAI scores did not differ significantly from before to after vaccination in SLE patients, although the level of anticardiolipin IgG increased at three weeks after vaccination, but with no apparent clinical manifestations. The A/H1N1 influenza vaccine is safe and effective in SLE patients and

  3. Sensitization with vaccinia virus encoding H5N1 hemagglutinin restores immune potential against H5N1 influenza virus.

    PubMed

    Yasui, Fumihiko; Itoh, Yasushi; Ikejiri, Ai; Kitabatake, Masahiro; Sakaguchi, Nobuo; Munekata, Keisuke; Shichinohe, Shintaro; Hayashi, Yukiko; Ishigaki, Hirohito; Nakayama, Misako; Sakoda, Yoshihiro; Kida, Hiroshi; Ogasawara, Kazumasa; Kohara, Michinori

    2016-11-28

    H5N1 highly pathogenic avian influenza (H5N1 HPAI) virus causes elevated mortality compared with seasonal influenza viruses like H1N1 pandemic influenza (H1N1 pdm) virus. We identified a mechanism associated with the severe symptoms seen with H5N1 HPAI virus infection. H5N1 HPAI virus infection induced a decrease of dendritic cell number in the splenic extrafollicular T-cell zone and impaired formation of the outer layers of B-cell follicles, resulting in insufficient levels of antibody production after infection. However, in animals vaccinated with a live recombinant vaccinia virus expressing the H5 hemagglutinin, infection with H5N1 HPAI virus induced parafollicular dendritic cell accumulation and efficient antibody production. These results indicate that a recombinant vaccinia encoding H5 hemagglutinin gene does not impair dendritic cell recruitment and can be a useful vaccine candidate.

  4. Immunogenicity and safety of pandemic influenza A (H1N1) 2009 vaccine: systematic review and meta-analysis.

    PubMed

    Yin, J Kevin; Khandaker, Gulam; Rashid, Harunor; Heron, Leon; Ridda, Iman; Booy, Robert

    2011-09-01

    The emergence of the 2009 H1N1 pandemic has highlighted the need to have immunogenicity and safety data on the new pandemic vaccines. There is already considerable heterogeneity in the types of vaccine available and of study performed around the world. A systematic review and meta-analysis is needed to assess the immunogenicity and safety of pandemic influenza A (H1N1) 2009 vaccines. We searched Medline, EMBASE, the Cochrane Library and other online databases up to 1st October 2010 for studies in any language comparing different pandemic H1N1 vaccines, with or without placebo, in healthy populations aged at least 6 months. The primary outcome was seroprotection according to haemagglutination inhibition (HI). Safety outcomes were adverse events. Meta-analysis was performed for the primary outcome. We identified 18 articles, 1 only on safety and 17 on immunogenicity, although 1 was a duplicate. We included 16 articles in the meta-analysis, covering 17,921 subjects. Adequate seroprotection (≥70%) was almost invariably achieved in all age groups, and even after one dose and at low antigen content (except in children under 3 years receiving one dose of non-adjuvanted vaccine). Non-adjuvanted vaccine from international companies and adjuvanted vaccines containing oil in water emulsion (e.g. AS03, MF59), rather than aluminium, performed better. Two serious vaccination-associated adverse events were reported, both of which resolved fully. No death or case of Guillain-Barré syndrome was reported. The pandemic influenza (H1N1) 2009 vaccine, with or without adjuvant, appears generally to be seroprotective after just one dose and safe among healthy populations aged ≥36 months; very young children (6-35 months) may need to receive two doses of non-adjuvanted vaccine or one dose of AS03(A/B)-adjuvanted product to achieve seroprotection. © 2011 Blackwell Publishing Ltd.

  5. Extrapolating theoretical efficacy of inactivated influenza A/H5N1 virus vaccine from human immunogenicity studies

    PubMed Central

    Feldstein, Leora R.; Matrajt, Laura; Halloran, M. Elizabeth; Keitel, Wendy A.; Longini, Ira M.

    2016-01-01

    Influenza A virus subtype H5N1 has been a public health concern for almost 20 years due to its potential ability to become transmissible among humans. Phase I and II clinical trials have assessed safety, reactogenicity and immunogenicity of inactivated influenza A/H5N1 virus vaccines. A shortage of vaccine is likely to occur during the first months of a pandemic. Hence, determining whether to give one dose to more people or two doses to fewer people to best protect the population is essential. We use hemagglutination-inhibition antibody titers as an immune correlate for avian influenza vaccines. Using an established relationship to obtain a theoretical vaccine efficacy from immunogenicity data from thirteen arms of six phase I and phase II clinical trials of inactivated influenza A/H5N1 virus vaccines, we assessed: 1) the proportion of theoretical vaccine efficacy achieved after a single dose (defined as primary response level), and 2) whether theoretical efficacy increases after a second dose, with and without adjuvant. Participants receiving vaccine with AS03 adjuvant had higher primary response levels (range: 0.48–0.57) compared to participants receiving vaccine with MF59 adjuvant (range: 0.32–0.47), with no observed trends in primary response levels by antigen dosage. After the first and second doses, vaccine with AS03 at dosage levels 3.75, 7.5 and 15 mcg had the highest estimated theoretical vaccine efficacy: Dose 1) 45% (95%CI: 36–57%), 53% (95%CI: 42–63%) and 55% (95%CI: 44–64%), respectively and Dose 2) 93% (95%CI: 89–96%), 97% (95%CI: 95–98%) and 97% (95%CI: 96–100%), respectively. On average, the estimated theoretical vaccine efficacy of lower dose adjuvanted vaccines (AS03 and MF59) was 17% higher than that of higher dose unadjuvanted vaccines, suggesting that including an adjuvant is dose-sparing. These data indicate adjuvanted inactivated influenza A/H5N1 virus vaccine produces high theoretical efficacy after two doses to protect

  6. Influenza A (H1N1) 2009 monovalent and seasonal influenza vaccination among adults 25 to 64 years of age with high-risk conditions—United States, 2010

    PubMed Central

    Lu, Peng-jun; Gonzalez-Feliciano, Amparo; Ding, Helen; Bryan, Leah N.; Yankey, David; Monsell, Elizabeth A.; Greby, Stacie M.; Euler, Gary L.

    2018-01-01

    Background Seasonal influenza vaccination has been routinely recommended for adults with high-risk conditions. The Advisory Committee on Immunization Practices recommended that persons 25 to 64 years of age with high-risk conditions be one of the initial target groups to receive H1N1 vaccination during the 2009-2010 season. Methods We used data from the 2009-2010 Behavioral Risk Factor Surveillance System survey. Vaccination levels of H1N1 and seasonal influenza vaccination among respondents 25 to 64 years with high-risk conditions were assessed. Multivariable logistic regression models were performed to identify factors independently associated with vaccination. Results Overall, 24.8% of adults 25 to 64 years of age were identified to have high-risk conditions. Among adults 25 to 64 years of age with high-risk conditions, H1N1 and seasonal vaccination coverage were 26.3% and 47.6%, respectively. Characteristics independently associated with an increased likelihood of H1N1 vaccination were as follows: higher age; Hispanic race/ethnicity; medical insurance; ability to see a doctor if needed; having a primary doctor; a routine checkup in the previous year; not being a current smoker; and having high-risk conditions other than asthma, diabetes, and heart disease. Characteristics independently associated with seasonal influenza vaccination were similar compared with factors associated with H1N1 vaccination. Conclusion Immunization programs should work with provider organizations to review efforts made to reach adults with high-risk conditions during the recent pandemic and assess how and where they can increase vaccination coverage during future pandemics. PMID:23419613

  7. Generation of a reassortant avian influenza virus H5N2 vaccine strain capable of protecting chickens against infection with Egyptian H5N1 and H9N2 viruses.

    PubMed

    Kandeil, Ahmed; Moatasim, Yassmin; Gomaa, Mokhtar R; Shehata, Mahmoud M; El-Shesheny, Rabeh; Barakat, Ahmed; Webby, Richard J; Ali, Mohamed A; Kayali, Ghazi

    2016-01-04

    Avian influenza H5N1 viruses have been enzootic in Egyptian poultry since 2006. Avian influenza H9N2 viruses which have been circulating in Egyptian poultry since 2011 showed high replication rates in embryonated chicken eggs and mammalian cells. To investigate which gene segment was responsible for increasing replication, we constructed reassortant influenza viruses using the low pathogenic H1N1 PR8 virus as backbone and included individual genes from A/chicken/Egypt/S4456B/2011(H9N2) virus. Then, we invested this finding to improve a PR8-derived H5N1 influenza vaccine strain by incorporation of the NA segment of H9N2 virus instead of the NA of H5N1. The growth properties of this virus and several other forms of reassortant H5 viruses were compared. Finally, we tested the efficacy of this reassortant vaccine strain in chickens. We observed an increase in replication for a reassortant virus expressing the neuraminidase gene (N2) of H9N2 virus relative to that of either parental viruses or reassortant PR8 viruses expressing other genes. Then, we generated an H5N2 vaccine strain based on the H5 from an Egyptian H5N1 virus and the N2 from an Egyptian H9N2 virus on a PR8 backbone. This strain had better replication rates than an H5N2 reassortant strain on an H9N2 backbone and an H5N1 reassortant on a PR8 backbone. This virus was then used to develop a killed, oil-emulsion vaccine and tested for efficacy against H5N1 and H9N2 viruses in chickens. Results showed that this vaccine was immunogenic and reduced mortality and shedding. Our findings suggest that an inactivated PR8-derived H5N2 influenza vaccine is efficacious in poultry against H5N1 and H9N2 viruses and the vaccine seed replicates at a high rate thus improving vaccine production. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Vaccination with Killed but Metabolically Active E. coli Over-expressing Hemagglutinin Elicits Neutralizing Antibodies to H1N1 Swine Origin Influenza A Virus

    PubMed Central

    Liu, Pei-Feng; Wang, Yanhan; Liu, Yu-Tsueng; Huang, Chun-Ming

    2017-01-01

    There is a need for a fast and simple method for vaccine production to keep up with the pace of a rapidly spreading virus in the early phases of the influenza pandemic. The use of whole viruses produced in chicken eggs or recombinant antigens purified from various expression systems has presented considerable challenges, especially with lengthy processing times. Here, we use the killed but metabolically active (KBMA) Escherichia coli (E. coli) to harbor the hemagglutinin (HA) of swine origin influenza A (H1N1) virus (S-OIV) San Diego/01/09 (SD/H1N1-S-OIV). Intranasal vaccination of mice with KBMA E. coli SD/H1N1-S-OIV HA without adding exogenous adjuvants provoked detectable neutralizing antibodies against the virus-induced hemagglutination within three weeks. Boosting vaccination enhanced the titers of neutralizing antibodies, which can decrease viral infectivity in Madin-Darby canine kidney (MDCK) cells. The antibodies were found to specifically neutralize the SD/H1N1-S-OIV-, but not seasonal influenza viruses (H1N1 and H3N2), -induced hemagglutination. The use of KBMA E. coli as an egg-free system to produce anti-influenza vaccines makes unnecessary the rigorous purification of an antigen prior to immunization, providing an alternative modality to combat influenza virus in future outbreaks. PMID:28492063

  9. Long-Term Immunogenicity of an Inactivated Split-Virion 2009 Pandemic Influenza A H1N1 Virus Vaccine with or without Aluminum Adjuvant in Mice

    PubMed Central

    Xu, Wenting; Zheng, Mei; Zhou, Feng

    2015-01-01

    In 2009, a global epidemic of influenza A(H1N1) virus caused the death of tens of thousands of people. Vaccination is the most effective means of controlling an epidemic of influenza and reducing the mortality rate. In this study, the long-term immunogenicity of influenza A/California/7/2009 (H1N1) split vaccine was observed as long as 15 months (450 days) after immunization in a mouse model. Female BALB/c mice were immunized intraperitoneally with different doses of aluminum-adjuvanted vaccine. The mice were challenged with a lethal dose (10× 50% lethal dose [LD50]) of homologous virus 450 days after immunization. The results showed that the supplemented aluminum adjuvant not only effectively enhanced the protective effect of the vaccine but also reduced the immunizing dose of the vaccine. In addition, the aluminum adjuvant enhanced the IgG antibody level of mice immunized with the H1N1 split vaccine. The IgG level was correlated to the survival rate of the mice. Aluminum-adjuvanted inactivated split-virion 2009 pandemic influenza A H1N1 vaccine has good immunogenicity and provided long-term protection against lethal influenza virus challenge in mice. PMID:25589552

  10. Treatment and Prevention of Pandemic H1N1 Influenza.

    PubMed

    Rewar, Suresh; Mirdha, Dashrath; Rewar, Prahlad

    2015-01-01

    Swine influenza is a respiratory infection common to pigs worldwide caused by type A influenza viruses, principally subtypes H1N1, H1N2, H2N1, H3N1, H3N2, and H2N3. Swine influenza viruses also can cause moderate to severe illness in humans and affect persons of all age groups. People in close contact with swine are at especially high risk. Until recently, epidemiological study of influenza was limited to resource-rich countries. The World Health Organization declared an H1N1 pandemic on June 11, 2009, after more than 70 countries reported 30,000 cases of H1N1 infection. In 2015, incidence of swine influenza increased substantially to reach a 5-year high. In India in 2015, 10,000 cases of swine influenza were reported with 774 deaths. The Centers for Disease Control and Prevention recommend real-time polymerase chain reaction as the method of choice for diagnosing H1N1. Antiviral drugs are the mainstay of clinical treatment of swine influenza and can make the illness milder and enable the patient to feel better faster. Antiviral drugs are most effective when they are started within the first 48 hours after the clinical signs begin, although they also may be used in severe or high-risk cases first seen after this time. The Centers for Disease Control and Prevention recommends use of oseltamivir (Tamiflu, Genentech) or zanamivir (Relenza, GlaxoSmithKline). Prevention of swine influenza has 3 components: prevention in swine, prevention of transmission to humans, and prevention of its spread among humans. Because of limited treatment options, high risk for secondary infection, and frequent need for intensive care of individuals with H1N1 pneumonia, environmental control, including vaccination of high-risk populations and public education are critical to control of swine influenza out breaks. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  11. Impacts of a mass vaccination campaign against pandemic H1N1 2009 influenza in Taiwan: a time-series regression analysis.

    PubMed

    Wu, Un-In; Wang, Jann-Tay; Chang, Shan-Chwen; Chuang, Yu-Chung; Lin, Wei-Ru; Lu, Min-Chi; Lu, Po-Liang; Hu, Fu-Chang; Chuang, Jen-Hsiang; Chen, Yee-Chun

    2014-06-01

    A multicenter, hospital-wide, clinical and epidemiological study was conducted to assess the effectiveness of the mass influenza vaccination program during the 2009 H1N1 influenza pandemic, and the impact of the prioritization strategy among people at different levels of risk. Among the 34 359 medically attended patients who displayed an influenza-like illness and had a rapid influenza diagnostic test (RIDT) at one of the three participating hospitals, 21.0% tested positive for influenza A. The highest daily number of RIDT-positive cases in each hospital ranged from 33 to 56. A well-fitted multiple linear regression time-series model (R(2)=0.89) showed that the establishment of special community flu clinics averted an average of nine cases daily (p=0.005), and an increment of 10% in daily mean level of population immunity against pH1N1 through vaccination prevented five cases daily (p<0.001). Moreover, the regression model predicted five-fold or more RIDT-positive cases if the mass influenza vaccination program had not been implemented, and 39.1% more RIDT-positive cases if older adults had been prioritized for vaccination above school-aged children. Mass influenza vaccination was an effective control measure, and school-aged children should be assigned a higher priority for vaccination than older adults during an influenza pandemic. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  12. H1N1 viral proteome peptide microarray predicts individuals at risk for H1N1 infection and segregates infection versus Pandemrix® vaccination

    PubMed Central

    Ambati, Aditya; Valentini, Davide; Montomoli, Emanuele; Lapini, Guilia; Biuso, Fabrizio; Wenschuh, Holger; Magalhaes, Isabelle; Maeurer, Markus

    2015-01-01

    A high content peptide microarray containing the entire influenza A virus [A/California/08/2009(H1N1)] proteome and haemagglutinin proteins from 12 other influenza A subtypes, including the haemagglutinin from the [A/South Carolina/1/1918(H1N1)] strain, was used to gauge serum IgG epitope signatures before and after Pandemrix® vaccination or H1N1 infection in a Swedish cohort during the pandemic influenza season 2009. A very narrow pattern of pandemic flu-specific IgG epitope recognition was observed in the serum from individuals who later contracted H1N1 infection. Moreover, the pandemic influenza infection generated IgG reactivity to two adjacent epitopes of the neuraminidase protein. The differential serum IgG recognition was focused on haemagglutinin 1 (H1) and restricted to classical antigenic sites (Cb) in both the vaccinated controls and individuals with flu infections. We further identified a novel epitope VEPGDKITFEATGNL on the Ca antigenic site (251–265) of the pandemic flu haemagglutinin, which was exclusively recognized in serum from individuals with previous vaccinations and never in serum from individuals with H1N1 infection (confirmed by RNA PCR analysis from nasal swabs). This epitope was mapped to the receptor-binding domain of the influenza haemagglutinin and could serve as a correlate of immune protection in the context of pandemic flu. The study shows that unbiased epitope mapping using peptide microarray technology leads to the identification of biologically and clinically relevant target structures. Most significantly an H1N1 infection induced a different footprint of IgG epitope recognition patterns compared with the pandemic H1N1 vaccine. PMID:25639813

  13. H5N1 vaccines in humans

    PubMed Central

    Baz, Mariana; Luke, Catherine J; Cheng, Xing; Jin, Hong; Subbarao, Kanta

    2013-01-01

    The spread of highly pathogenic avian H5N1 influenza viruses since 1997 and their virulence for poultry and humans has raised concerns about their potential to cause an influenza pandemic. Vaccines offer the most viable means to combat a pandemic threat. However, it will be a challenge to produce, distribute and implement a new vaccine if a pandemic spreads rapidly. Therefore, efforts are being undertaken to develop pandemic vaccines that use less antigen and induce cross-protective and long-lasting responses, that can be administered as soon as a pandemic is declared or possibly even before, in order to prime the population and allow for a rapid and protective antibody response. In the last few years, several vaccine manufacturers have developed candidate pandemic and pre-pandemic vaccines, based on reverse genetics and have improved the immunogenicity by formulating these vaccines with different adjuvants. Some of the important and consistent observations from clinical studies with H5N1 vaccines are as follows: two doses of inactivated vaccine are generally necessary to elicit the level of immunity required to meet licensure criteria, less antigen can be used if an oil-in-water adjuvant is included, in general antibody titers decline rapidly but can be boosted with additional doses of vaccine and if high titers of antibody are elicited, cross-reactivity against other clades is observed. Prime-boost strategies elicit a more robust immune response. In this review, we discuss data from clinical trials with a variety of H5N1 influenza vaccines. We also describe studies conducted in animal models to explore the possibility of reassortment between pandemic live attenuated vaccine candidates and seasonal influenza viruses, since this is an important consideration for the use of live vaccines in a pandemic setting. PMID:23726847

  14. Vaccination with virus-like particles containing H5 antigens from three H5N1 clades protects chickens from H5N1 and H5N8 influenza viruses

    USDA-ARS?s Scientific Manuscript database

    Highly pathogenic avian influenza (HPAI) viruses, especially H5N1 strains, represent a public health threat and cause widespread morbidity and mortality in domestic poultry. Recombinant virus-like particles (VLPs) represent a promising novel vaccine approach to control avian influenza including HPAI...

  15. Obstetricians and the 2009-2010 H1N1 vaccination effort: implications for future pandemics.

    PubMed

    Clark, Sarah J; Cowan, Anne E; Wortley, Pascale M

    2013-09-01

    Our objective was to describe the experiences of obstetricians during the 2009-2010 H1N1 vaccination campaign in order to identify possible improvements for future pandemic situations. We conducted a cross-sectional mail survey of a national random sample of 4,000 obstetricians, fielded in Summer 2010. Survey items included availability, recommendation, and patient acceptance of H1N1 vaccine; prioritization of H1N1 vaccine when supply was limited; problems with H1N1 vaccination; and likelihood of providing vaccine during a future influenza pandemic. Response rate was 66 %. Obstetricians strongly recommended H1N1 vaccine during the second (85 %) and third (86 %) trimesters, and less often during the first trimester (71 %) or the immediate postpartum period (76 %); patient preferences followed a similar pattern. H1N1 vaccine was typically available in outpatient obstetrics clinics (80 %). Overall vaccine supply was a major problem for 30 % of obstetricians, but few rated lack of thimerosal-free vaccine as a major problem (12 %). Over half of obstetricians had no major problems with the H1N1 vaccine campaign. Based on this experience, 74 % would be "very likely" and 12 % "likely" to provide vaccine in the event of a future influenza pandemic. Most obstetricians strongly recommended H1N1 vaccine, had few logistical problems beyond limited vaccine supply, and are willing to vaccinate in a future pandemic. Addressing concerns about first-trimester vaccination, developing guidance for prioritization of vaccine in the event of severe supply constraints, and continued facilitation of the logistical aspects of vaccination should be emphasized in future influenza pandemics.

  16. A Live Attenuated Influenza A(H5N1) Vaccine Induces Long-Term Immunity in the Absence of a Primary Antibody Response

    PubMed Central

    Talaat, Kawsar R.; Luke, Catherine J.; Khurana, Surender; Manischewitz, Jody; King, Lisa R.; McMahon, Bridget A.; Karron, Ruth A.; Lewis, Kristen D. C.; Qin, Jing; Follmann, Dean A.; Golding, Hana; Neuzil, Kathleen M.; Subbarao, Kanta

    2014-01-01

    Background. Highly pathogenic avian influenza A(H5N1) causes severe infections in humans. We generated 2 influenza A(H5N1) live attenuated influenza vaccines for pandemic use (pLAIVs), but they failed to elicit a primary immune response. Our objective was to determine whether the vaccines primed or established long-lasting immunity that could be detected by administration of inactivated subvirion influenza A(H5N1) vaccine (ISIV). Methods. The following groups were invited to participate in the study: persons who previously received influenza A(H5N1) pLAIV; persons who previously received an irrelevant influenza A(H7N3) pLAIV; and community members who were naive to influenza A(H5N1) and LAIV. LAIV-experienced subjects received a single 45-μg dose of influenza A(H5N1) ISIV. Influenza A(H5N1)– and LAIV-naive subjects received either 1 or 2 doses of ISIV. Results. In subjects who had previously received antigenically matched influenza A(H5N1) pLAIV followed by 1 dose of ISIV compared with those who were naive to influenza A(H5N1) and LAIV and received 2 doses of ISIV, we observed an increased frequency of antibody response (82% vs 50%, by the hemagglutination inhibition assay) and a significantly higher antibody titer (112 vs 76; P = .04). The affinity of antibody and breadth of cross-clade neutralization was also enhanced in influenza A(H5N1) pLAIV–primed subjects. Conclusions. ISIV administration unmasked long-lasting immunity in influenza A(H5N1) pLAIV recipients, with a rapid, high-titer, high-quality antibody response that was broadly cross-reactive across several influenza A(H5N1) clades. Clinical Trials Registration. NCT01109329. PMID:24604819

  17. Vaccination against the 2009 pandemic influenza A (H1N1) among healthcare workers in the major teaching hospital of Sicily (Italy).

    PubMed

    Amodio, Emanuele; Anastasi, Giovanna; Marsala, Maria Grazia Laura; Torregrossa, Maria Valeria; Romano, Nino; Firenze, Alberto

    2011-02-04

    The aim of the study was to investigate factors involved in vaccination acceptance among healthcare workers (HCWs) and adverse reactions rates associated with pandemic influenza vaccination. The study was carried out in the major teaching hospital of Sicily from November 2009 to February 2010 on 2267 HCWs. A total of 407 (18%) HCWs were vaccinated against the 2009 pandemic influenza A (H1N1). A logistic regression analysis indicates an increased risk of non-vaccination against pandemic influenza in females (OR=1.6; 95% CI=1.3-2.1) compared to males, in nurses/technicians/administrative workers (OR=1.7; 95% CI=1.3-2.2) compared to doctors/biologists, and in HCWs who were non-vaccinated against seasonal influenza in 2008-2009 (OR=4.9; 95% CI=3.7-6.5) compared to vaccinated HCWs. Overall, 302 (74.2%) out of 407 questionnaires distributed to vaccinated HCWs were returned within the observation period. One hundred fifty-two workers (50.3%) experienced at least one adverse reaction (30.1%, local reactions; 6.6% systemic reactions and 13.6% both of them). The most frequent side effect of vaccination was pain at the injection site (43.4%). Twelve (3.9%) out of 302 HCWs stated they experienced influenza-like illness episodes during the follow-up period. The use of an adjuvanted vaccine against pandemic influenza A (H1N1) appears to be an effective and safe preventive strategy, showing a prevalence of both local and systemic adverse reactions not very different from that seen after vaccination with non-adjuvanted seasonal influenza vaccine. Despite this finding, vaccination coverage among HCWs remains very low, suggesting the need to implement educational campaigns directed to groups with lower coverage rates. Copyright © 2010 Elsevier Ltd. All rights reserved.

  18. Sustained low influenza vaccination in health care workers after H1N1 pandemic: a cross sectional study in an Italian health care setting for at-risk patients.

    PubMed

    Giannattasio, Antonietta; Mariano, Miriam; Romano, Roberto; Chiatto, Fabrizia; Liguoro, Ilaria; Borgia, Guglielmo; Guarino, Alfredo; Lo Vecchio, Andrea

    2015-08-12

    Despite consistent recommendations by all Public Health Authorities in support of annual influenza vaccination for at-risk categories, there is still a low uptake of influenza vaccine in these groups including health care workers (HCWs). Aim of this observational two-phase study was to estimate the immunization rates for influenza in four subsequent seasons and for pandemic H1N1 influenza in HCWs of a University Hospital, and to investigate its distribution pattern and the main determinants of immunization. Phase 1 data collection was performed in 2009-2010, during the peak of H1N1 pandemic. Phase 2 data collection, aimed to investigate seasonal influenza vaccination coverage in the three seasons after pandemic, was performed in 2012-2013. The overall H1N1 vaccination rate was derived by the Hospital immunization registry. In 2010, the personnel of three Departments (Infectious Diseases, Pediatrics and Gynecology/Obstetrics) completed a survey on influenza. A second-phase analysis was performed in 2012 to investigate influenza vaccination coverage in three consecutive seasons. The first-phase survey showed a low coverage for influenza in all categories (17 %), with the lowest rate in nurses (8.1 %). A total of 37 % of health care workers received H1N1 vaccine, with the highest rate among physicians and the lowest in nurses. H1N1 vaccination was closely related to the Department, being higher in the Department of Infectious Diseases (53.7 %) and Pediatrics (42.4 %) than in Gynecology/Obstetrics (8.3 %). The second-phase survey showed the lowest rate of influenza vaccination in 2012/13 season. The main reasons for not being vaccinated were "Unsure of the efficacy of vaccine" and "Feel not at-risk of getting influenza or its complications". Despite recommendations, influenza vaccine uptake remains poor. Immunization is largely perceived as a personal protection rather than a measure needed to prevent disease spreading to at-risk patients. Compulsory vaccination

  19. Optimal H1N1 vaccination strategies based on self-interest versus group interest.

    PubMed

    Shim, Eunha; Meyers, Lauren Ancel; Galvani, Alison P

    2011-02-25

    Influenza vaccination is vital for reducing H1N1 infection-mediated morbidity and mortality. To reduce transmission and achieve herd immunity during the initial 2009-2010 pandemic season, the US Centers for Disease Control and Prevention (CDC) recommended that initial priority for H1N1 vaccines be given to individuals under age 25, as these individuals are more likely to spread influenza than older adults. However, due to significant delay in vaccine delivery for the H1N1 influenza pandemic, a large fraction of population was exposed to the H1N1 virus and thereby obtained immunity prior to the wide availability of vaccines. This exposure affects the spread of the disease and needs to be considered when prioritizing vaccine distribution. To determine optimal H1N1 vaccine distributions based on individual self-interest versus population interest, we constructed a game theoretical age-structured model of influenza transmission and considered the impact of delayed vaccination. Our results indicate that if individuals decide to vaccinate according to self-interest, the resulting optimal vaccination strategy would prioritize adults of age 25 to 49 followed by either preschool-age children before the pandemic peak or older adults (age 50-64) at the pandemic peak. In contrast, the vaccine allocation strategy that is optimal for the population as a whole would prioritize individuals of ages 5 to 64 to curb a growing pandemic regardless of the timing of the vaccination program. Our results indicate that for a delayed vaccine distribution, the priorities that are optimal at a population level do not align with those that are optimal according to individual self-interest. Moreover, the discordance between the optimal vaccine distributions based on individual self-interest and those based on population interest is even more pronounced when vaccine availability is delayed. To determine optimal vaccine allocation for pandemic influenza, public health agencies need to consider

  20. Human infection with highly pathogenic H5N1 influenza virus.

    PubMed

    Gambotto, Andrea; Barratt-Boyes, Simon M; de Jong, Menno D; Neumann, Gabriele; Kawaoka, Yoshihiro

    2008-04-26

    Highly pathogenic H5N1 influenza A viruses have spread relentlessly across the globe since 2003, and they are associated with widespread death in poultry, substantial economic loss to farmers, and reported infections of more than 300 people with a mortality rate of 60%. The high pathogenicity of H5N1 influenza viruses and their capacity for transmission from birds to human beings has raised worldwide concern about an impending human influenza pandemic similar to the notorious H1N1 Spanish influenza of 1918. Since many aspects of H5N1 influenza research are rapidly evolving, we aim in this Seminar to provide an up-to-date discussion on select topics of interest to influenza clinicians and researchers. We summarise the clinical features and diagnosis of infection and present therapeutic options for H5N1 infection of people. We also discuss ideas relating to virus transmission, host restriction, and pathogenesis. Finally, we discuss vaccine development in view of the probable importance of vaccination in pandemic control.

  1. Comparative safety, immunogenicity, and efficacy of several anti‐H5N1 influenza experimental vaccines in a mouse and chicken models (Testing of killed and live H5 vaccine)

    PubMed Central

    Gambaryan, Alexandra S.; Lomakina, Natalia F.; Boravleva, Elizaveta Y.; Kropotkina, Ekaterina A.; Mashin, Vadim V.; Krasilnikov, Igor V.; Klimov, Alexander I.; Rudenko, Larisa G.

    2011-01-01

    Please cite this paper as: Gambaryan et al. (2011) Comparative safety, immunogenicity, and efficacy of several anti‐H5N1 influenza experimental vaccines in a mouse and chicken models. Parallel testing of killed and live H5 vaccine. Influenza and Other Respiratory Viruses 6(3), 188–195. Objective  Parallel testing of inactivated (split and whole virion) and live vaccine was conducted to compare the immunogenicity and protective efficacy against homologous and heterosubtypic challenge by H5N1 highly pathogenic avian influenza virus. Method  Four experimental live vaccines based on two H5N1 influenza virus strains were tested; two of them had hemagglutinin (HA) of A/Vietnam/1203/04 strain lacking the polybasic HA cleavage site, and two others had hemagglutinins from attenuated H5N1 virus A/Chicken/Kurgan/3/05, with amino acid substitutions of Asp54/Asn and Lys222/Thr in HA1 and Val48/Ile and Lys131/Thr in HA2 while maintaining the polybasic HA cleavage site. The neuraminidase and non‐glycoprotein genes of the experimental live vaccines were from H2N2 cold‐adapted master strain A/Leningrad/134/17/57 (VN‐Len and Ku‐Len) or from the apathogenic H6N2 virus A/Gull/Moscow/3100/2006 (VN‐Gull and Ku‐Gull). Inactivated H5N1 and H1N1 and live H1N1 vaccine were used for comparison. All vaccines were applied in a single dose. Safety, immunogenicity, and protectivity against the challenge with HPAI H5N1 virus A/Chicken/Kurgan/3/05 were estimated. Results  All experimental live H5 vaccines tested were apathogenic as determined by weight loss and conferred more than 90% protection against lethal challenge with A/Chicken/Kurgan/3/05 infection. Inactivated H1N1 vaccine in mice offered no protection against challenge with H5N1 virus, while live cold‐adapted H1N1 vaccine reduced the mortality near to zero level. Conclusions  The high yield, safety, and protectivity of VN‐Len and Ku‐Len made them promising strains for the production of inactivated and live

  2. Prior infection of chickens with H1N1 or H1N2 avian influenza elicits partial heterologous protection against highly pathogenic H5N1.

    PubMed

    Nfon, Charles; Berhane, Yohannes; Pasick, John; Embury-Hyatt, Carissa; Kobinger, Gary; Kobasa, Darwyn; Babiuk, Shawn

    2012-01-01

    There is a critical need to have vaccines that can protect against emerging pandemic influenza viruses. Commonly used influenza vaccines are killed whole virus that protect against homologous and not heterologous virus. Using chickens we have explored the possibility of using live low pathogenic avian influenza (LPAI) A/goose/AB/223/2005 H1N1 or A/WBS/MB/325/2006 H1N2 to induce immunity against heterologous highly pathogenic avian influenza (HPAI) A/chicken/Vietnam/14/2005 H5N1. H1N1 and H1N2 replicated in chickens but did not cause clinical disease. Following infection, chickens developed nucleoprotein and H1 specific antibodies, and reduced H5N1 plaque size in vitro in the absence of H5 neutralizing antibodies at 21 days post infection (DPI). In addition, heterologous cell mediated immunity (CMI) was demonstrated by antigen-specific proliferation and IFN-γ secretion in PBMCs re-stimulated with H5N1 antigen. Following H5N1 challenge of both pre-infected and naïve controls chickens housed together, all naïve chickens developed acute disease and died while H1N1 or H1N2 pre-infected chickens had reduced clinical disease and 70-80% survived. H1N1 or H1N2 pre-infected chickens were also challenged with H5N1 and naïve chickens placed in the same room one day later. All pre-infected birds were protected from H5N1 challenge but shed infectious virus to naïve contact chickens. However, disease onset, severity and mortality was reduced and delayed in the naïve contacts compared to directly inoculated naïve controls. These results indicate that prior infection with LPAI virus can generate heterologous protection against HPAI H5N1 in the absence of specific H5 antibody.

  3. Prior Infection of Chickens with H1N1 or H1N2 Avian Influenza Elicits Partial Heterologous Protection against Highly Pathogenic H5N1

    PubMed Central

    Nfon, Charles; Berhane, Yohannes; Pasick, John; Embury-Hyatt, Carissa; Kobinger, Gary; Kobasa, Darwyn; Babiuk, Shawn

    2012-01-01

    There is a critical need to have vaccines that can protect against emerging pandemic influenza viruses. Commonly used influenza vaccines are killed whole virus that protect against homologous and not heterologous virus. Using chickens we have explored the possibility of using live low pathogenic avian influenza (LPAI) A/goose/AB/223/2005 H1N1 or A/WBS/MB/325/2006 H1N2 to induce immunity against heterologous highly pathogenic avian influenza (HPAI) A/chicken/Vietnam/14/2005 H5N1. H1N1 and H1N2 replicated in chickens but did not cause clinical disease. Following infection, chickens developed nucleoprotein and H1 specific antibodies, and reduced H5N1 plaque size in vitro in the absence of H5 neutralizing antibodies at 21 days post infection (DPI). In addition, heterologous cell mediated immunity (CMI) was demonstrated by antigen-specific proliferation and IFN-γ secretion in PBMCs re-stimulated with H5N1 antigen. Following H5N1 challenge of both pre-infected and naïve controls chickens housed together, all naïve chickens developed acute disease and died while H1N1 or H1N2 pre-infected chickens had reduced clinical disease and 70–80% survived. H1N1 or H1N2 pre-infected chickens were also challenged with H5N1 and naïve chickens placed in the same room one day later. All pre-infected birds were protected from H5N1 challenge but shed infectious virus to naïve contact chickens. However, disease onset, severity and mortality was reduced and delayed in the naïve contacts compared to directly inoculated naïve controls. These results indicate that prior infection with LPAI virus can generate heterologous protection against HPAI H5N1 in the absence of specific H5 antibody. PMID:23240067

  4. Twin Peaks: A/H1N1 Pandemic Influenza Virus Infection and Vaccination in Norway, 2009–2010

    PubMed Central

    Van Effelterre, Thierry; Dos Santos, Gaël; Shinde, Vivek

    2016-01-01

    Background Vaccination campaigns against A/H1N1 2009 pandemic influenza virus (A/H1N1p) began in autumn 2009 in Europe, after the declaration of the pandemic at a global level. This study aimed to estimate the proportion of individuals vaccinated against A/H1N1p in Norway who were already infected (asymptomatically or symptomatically) by A/H1N1p before vaccination, using a mathematical model. Methods A dynamic, mechanistic, mathematical model of A/H1N1p transmission was developed for the Norwegian population. The model parameters were estimated by calibrating the model-projected number of symptomatic A/H1N1p cases to the number of laboratory-confirmed A/H1N1p cases reported to the surveillance system, accounting for potential under-reporting. It was assumed in the base case that the likelihood of vaccination was independent of infection/disease state. A sensitivity analysis explored the effects of four scenarios in which current or previous symptomatic A/H1N1p infection would influence the likelihood of being vaccinated. Results The number of model-projected symptomatic A/H1N1p cases by week during the epidemic, accounting for under-reporting and timing, closely matched that of the laboratory-confirmed A/H1N1p cases reported to the surveillance system. The model-projected incidence of symptomatic A/H1N1p infection was 27% overall, 55% in people <10 years old and 41% in people 10–20 years old. The model-projected percentage of individuals vaccinated against A/H1N1p who were already infected with A/H1N1p before being vaccinated was 56% overall, 62% in people <10 years old and 66% in people 10–20 years old. The results were sensitive to assumptions about the independence of vaccination and infection; however, even when current or previous symptomatic A/H1N1p infection was assumed to reduce the likelihood of vaccination, the estimated percentage of individuals who were infected before vaccination remained at least 32% in all age groups. Conclusion This analysis

  5. A systematic review and meta-analysis of fetal outcomes following the administration of influenza A/H1N1 vaccination during pregnancy.

    PubMed

    Zhang, Chuan; Wang, Xiaodong; Liu, Dan; Zhang, Lingli; Sun, Xin

    2018-05-01

    Pregnant women were identified as a population of priority for vaccination during the H1N1 influenza pandemic outbreak in 2009. To assess adverse fetal outcomes following the administration of H1N1 pandemic vaccination during pregnancy. PubMed, Embase, and Cochrane Library were searched up to January 2017. Cohort studies investigating fetal outcomes after H1N1 influenza vaccination during pregnancy were eligible. The language was limited to English. Pairs of reviewers independently screened studies for eligibility, assessed the risk of bias, and extracted data from the included studies. A total of 19 cohort studies were eligible. The use of vaccines during any period of pregnancy was associated with lower risk of stillbirth (adjusted hazard ratio 0.80, 95% confidence interval 0.69-0.92). No significant differences were found between the vaccinated versus unvaccinated groups in terms of the risks of spontaneous abortion, premature birth, and small for gestational age. The administration of H1N1 vaccines during pregnancy might reduce the risk of stillbirth, a complication associated with H1N1 infection. The quality of evidence was, however, not adequate to reach a definitive conclusion. © 2017 International Federation of Gynecology and Obstetrics.

  6. Antibody response to influenza A(H1N1)pdm09 among healthcare personnel receiving trivalent inactivated vaccine: effect of prior monovalent inactivated vaccine.

    PubMed

    Gaglani, Manjusha; Spencer, Sarah; Ball, Sarah; Song, Juhee; Naleway, Allison; Henkle, Emily; Bozeman, Sam; Reynolds, Sue; Sessions, Wendy; Hancock, Kathy; Thompson, Mark

    2014-06-01

    Few data are available on the immunogenicity of repeated annual doses of influenza A(H1N1)pdm09-containing vaccines. We enrolled healthcare personnel (HCP) in direct patient care during the autumn of 2010 at 2 centers with voluntary immunization. We verified the receipt of A(H1N1)pdm09-containing monovalent inactivated influenza vaccine (MIIV) and 2010-2011 trivalent inactivated vaccine (TIV). We performed hemagglutination inhibition antibody (HI) assays on preseason, post-TIV, and end-of-season serum samples. We compared the proportion of HCPs with HI titer ≥ 40 against A(H1N1)pdm09 per receipt of prior-season MIIV, current-season TIV, both, or neither. At preseason (n = 1417), HI ≥ 40 was significantly higher among those who received MIIV (34%) vs those who did not (14%) (adjusted relative risk [ARR], 3.26; 95% confidence interval [CI], 2.72-3.81). At post-TIV (n = 865), HI ≥ 40 was lower among HCP who received MIIV and TIV (66%) than among those receiving only TIV (85%) (ARR, 0.93 [95% CI, .84-.997]). At end-of-season (n = 1254), HI ≥ 40 was 40% among those who received both MIIV and TIV and 67% among those receiving only TIV (ARR, 0.76 [95% CI, .65-.88]), 52% among those who received MIIV only, and 12% among those receiving neither. HCP immunization programs should consider effects of host immune response and vaccine antigenic distance on immunogenicity of repeated annual doses of influenza vaccines.

  7. H1N1 vaccination in pediatric renal transplant patients.

    PubMed

    Kelen, K; Ferenczi, D; Jankovics, I; Varga, M; Molnar, M Z; Sallay, P; Reusz, G; Langer, R M; Pasti, K; Gerlei, Z; Szabo, A J

    2011-05-01

    Solid organ transplant recipients undergoing immunosuppressive therapy are considered to be at high risk of serious infectious complications. In 2009, a new influenza pandemic caused serious infections and deaths, especially among children and immunocompromised patients. Herein we have reported the safety and efficacy of a single-shot monovalent whole-virus vaccine against H1N1 infection in the pediatric renal transplant population. In November and December 2009, we vaccinated 37 renal transplant children and adolescents and measured their antibody responses. Seroprotection, seroconversion, and seroconversion factors were analyzed at 21 days after vaccination. None of the vaccinated patients experienced vaccine-related side effects. None of the patients had an H1N1 influenza infection after vaccination. All of the patients showed elevations in antibody titer at 21 days after vaccination. In contrast, only 29.72% of the patients achieved a safe seroprotection level and only 18.75% a safe seroconversion rate. More intense immunosuppressive treatment displayed negative effect on seroprotection and seroconversion, and antibody production significantly increased with age. No other factor was observed to influence seroprotection. We recommend vaccination of children and adolescent renal transplant recipients against H1N1 virus. However, a single shot of vaccine may not be sufficient; to achieve seroprotection, a booster vaccination and measurement of the antibody response are needed to assure protection of our patients. Copyright © 2011 Elsevier Inc. All rights reserved.

  8. Antibody responses to influenza A/H1N1pdm09 virus after pandemic and seasonal influenza vaccination in healthcare workers: a five-year follow-up study.

    PubMed

    Trieu, Mai-Chi; Jul-Larsen, Åsne; Sævik, Marianne; Madsen, Anders; Nøstbakken, Jane Kristin; Zhou, Fan; Skrede, Steinar; Cox, Rebecca Jane

    2018-06-09

    The 2009 influenza pandemic was caused by A/H1N1pdm09 virus, which was subsequently included in the seasonal vaccine as the A/H1N1 strain up to 2016/17. This provided a unique opportunity to investigate the antibody response to H1N1pdm09 over time. Healthcare workers (HCWs) were immunized with the AS03-adjuvanted H1N1pdm09 vaccine in 2009 (N=250), and subsequently vaccinated with seasonal vaccines containing H1N1pdm09 for 4 seasons (repeated group), <4 seasons (occasional group), or received no further vaccinations (single group). Blood samples were collected at 21-days, 3-, 6- and 12-months after each vaccination or annually (pre-season) from 2010 in the single group. The H1N1pdm09-specific antibodies were measured by the hemagglutination inhibition (HI) assay. Pandemic vaccination robustly induced HI antibodies that persisted above the 50% protective threshold (HI titers ≥40) over 12-months post-vaccination. Previous seasonal vaccination and the duration of adverse events after pandemic vaccination influenced the decision to vaccinate in subsequent seasons. During 2010/11-2013/14, antibodies were boosted after each seasonal vaccination, although no significant difference was observed between the repeated and occasional groups. In the single group without seasonal vaccination, 32% of HCWs seroconverted (≥4 fold-increase HI titers) during the four subsequent years, most of whom had HI titers <40 prior to seroconversion. When excluding these seroconverted HCWs, HI titers gradually declined from 12- to 60-months post-pandemic vaccination. Pandemic vaccination elicited durable antibodies, supporting the incorporation of adjuvant. Our findings support the current recommendation of annual influenza vaccination in HCWs.

  9. Modelling the risk-benefit impact of H1N1 influenza vaccines.

    PubMed

    Phillips, Lawrence D; Fasolo, Barbara; Zafiropoulous, Nikolaos; Eichler, Hans-Georg; Ehmann, Falk; Jekerle, Veronika; Kramarz, Piotr; Nicoll, Angus; Lönngren, Thomas

    2013-08-01

    Shortly after the H1N1 influenza virus reached pandemic status in June 2009, the benefit-risk project team at the European Medicines Agency recognized this presented a research opportunity for testing the usefulness of a decision analysis model in deliberations about approving vaccines soon based on limited data or waiting for more data. Undertaken purely as a research exercise, the model was not connected to the ongoing assessment by the European Medicines Agency, which approved the H1N1 vaccines on 25 September 2009. A decision tree model constructed initially on 1 September 2009, and slightly revised subsequently as new data were obtained, represented an end-of-September or end-of-October approval of vaccines. The model showed combinations of uncertain events, the severity of the disease and the vaccines' efficacy and safety, leading to estimates of numbers of deaths and serious disabilities. The group based their probability assessments on available information and background knowledge about vaccines and similar pandemics in the past. Weighting the numbers by their joint probabilities for all paths through the decision tree gave a weighted average for a September decision of 216 500 deaths and serious disabilities, and for a decision delayed to October of 291 547, showing that an early decision was preferable. The process of constructing the model facilitated communications among the group's members and led to new insights for several participants, while its robustness built confidence in the decision. These findings suggest that models might be helpful to regulators, as they form their preferences during the process of deliberation and debate, and more generally, for public health issues when decision makers face considerable uncertainty.

  10. Virological characterization of influenza H1N1pdm09 in Vietnam, 2010-2013.

    PubMed

    Nguyen, Hang K L; Nguyen, Phuong T K; Nguyen, Thach C; Hoang, Phuong V M; Le, Thanh T; Vuong, Cuong D; Nguyen, Anh P; Tran, Loan T T; Nguyen, Binh G; Lê, Mai Q

    2015-07-01

    Influenza A/H1N1pdm09 virus was first detected in Vietnam on May 31, 2009, and continues to circulate in Vietnam as a seasonal influenza virus. This study has monitored genotypic and phenotypic changes in this group of viruses during 2010-2013 period. We sequenced hemagglutinin (HA) and neuraminidase (NA) genes from representative influenza A/H1N1pdm09 and compared with vaccine strain A/California/07/09 and other contemporary isolates from neighboring countries. Hemagglutination inhibition (HI) and neuraminidase inhibition (NAI) assays also were performed on these isolates. Representative influenza A/H1N1pdm09 isolates (n = 61) from ILI and SARI surveillances in northern Vietnam between 2010 and 2013. The HA and NA phylogenies revealed six and seven groups, respectively. Five isolates (8·2%) had substitutions G155E and N156K in the HA, which were associated with reduced HI titers by antiserum raised against the vaccine virus A/California/07/2009. One isolate from 2011 and one isolate from 2013 had a predicted H275Y substitution in the neuraminidase molecule, which was associated with reduced susceptibility to oseltamivir in a NAI assay. We also identified a D222N change in the HA of a virus isolated from a fatal case in 2013. Significant genotypic and phenotypic changes in A/ H1N1pdm09 influenza viruses were detected by the National Influenza Surveillance System (NISS) in Vietnam between 2010 and 2013 highlighting the value of this system to Vietnam and to the region. Sustained NISS and continued virological monitoring of seasonal influenza viruses are required for vaccine policy development in Vietnam. 3. © 2015 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.

  11. Development of a dual-protective live attenuated vaccine against H5N1 and H9N2 avian influenza viruses by modifying the NS1 gene.

    PubMed

    Choi, Eun-hye; Song, Min-Suk; Park, Su-Jin; Pascua, Philippe Noriel Q; Baek, Yun Hee; Kwon, Hyeok-il; Kim, Eun-Ha; Kim, Semi; Jang, Hyung-Kwan; Poo, Haryoung; Kim, Chul-Joong; Choi, Young Ki

    2015-07-01

    An increasing number of outbreaks of avian influenza H5N1 and H9N2 viruses in poultry have caused serious economic losses and raised concerns for human health due to the risk of zoonotic transmission. However, licensed H5N1 and H9N2 vaccines for animals and humans have not been developed. Thus, to develop a dual H5N1 and H9N2 live-attenuated influenza vaccine (LAIV), the HA and NA genes from a virulent mouse-adapted avian H5N2 (A/WB/Korea/ma81/06) virus and a recently isolated chicken H9N2 (A/CK/Korea/116/06) virus, respectively, were introduced into the A/Puerto Rico/8/34 backbone expressing truncated NS1 proteins (NS1-73, NS1-86, NS1-101, NS1-122) but still possessing a full-length NS gene. Two H5N2/NS1-LAIV viruses (H5N2/NS1-86 and H5N2/NS1-101) were highly attenuated compared with the full-length and remaining H5N2/NS-LAIV viruses in a mouse model. Furthermore, viruses containing NS1 modifications were found to induce more IFN-β activation than viruses with full-length NS1 proteins and were correspondingly attenuated in mice. Intranasal vaccination with a single dose (10(4.0) PFU/ml) of these viruses completely protected mice from a lethal challenge with the homologous A/WB/Korea/ma81/06 (H5N2), heterologous highly pathogenic A/EM/Korea/W149/06 (H5N1), and heterosubtypic highly virulent mouse-adapted H9N2 viruses. This study clearly demonstrates that the modified H5N2/NS1-LAIV viruses attenuated through the introduction of mutations in the NS1 coding region display characteristics that are desirable for live attenuated vaccines and hold potential as vaccine candidates for mammalian hosts.

  12. Cross-reactivity to highly pathogenic avian influenza H5N1 viruses after vaccination with nonadjuvanted and MF59-adjuvanted influenza A/Duck/Singapore/97 (H5N3) vaccine: a potential priming strategy.

    PubMed

    Stephenson, Iain; Bugarini, Roberto; Nicholson, Karl G; Podda, Audino; Wood, John M; Zambon, Maria C; Katz, Jacqueline M

    2005-04-15

    Antigenically well-matched vaccines against highly pathogenic avian influenza H5N1 viruses are urgently required. Human serum samples after immunization with MF59 or nonadjuvanted A/duck/Singapore/97 (H5N3) vaccine were tested for antibody to 1997-2004 human H5N1 viruses. Antibody responses to 3 doses of nonadjuvanted vaccine were poor and were higher after MF59-adjuvanted vaccine, with seroconversion rates to A/HongKong/156/97, A/HongKong/213/03, A/Thailand/16/04, and A/Vietnam/1203/04 of 100% (P < .0001), 100% (P < .0001), 71% (P = .0004), and 43% (P = .0128) in 14 subjects, respectively, compared with 27%, 27%, 0%, and 0% in 11 who received nonadjuvanted vaccine. These findings have implications for the rational design of pandemic vaccines against influenza H5.

  13. A/H1N1 pandemic influenza vaccination: A retrospective evaluation of adverse maternal, fetal and neonatal outcomes in a cohort of pregnant women in Italy.

    PubMed

    Fabiani, Massimo; Bella, Antonino; Rota, Maria C; Clagnan, Elena; Gallo, Tolinda; D'Amato, Maurizio; Pezzotti, Patrizio; Ferrara, Lorenza; Demicheli, Vittorio; Martinelli, Domenico; Prato, Rosa; Rizzo, Caterina

    2015-05-05

    Although concerns about safety of influenza vaccination during pregnancy have been raised in the past, vaccination of pregnant women was recommended in many countries during the 2009 A/H1N1 pandemic influenza. A retrospective cohort study was conducted to evaluate the risk of adverse maternal, fetal and neonatal outcomes among pregnant women vaccinated with a MF59-adjuvanted A/H1N1 pandemic influenza vaccine. The study was carried out in four Italian regions (Piemonte, Friuli-Venezia-Giulia, Lazio, and Puglia) among 102,077 pregnant women potentially exposed during the second or third trimester of gestation to the vaccination campaign implemented in 2009/2010. Based on data retrieved from the regional administrative databases, the statistical analysis was performed using the Cox proportional-hazards model, adjusting for the propensity score to account for the potential confounding effect due to the socio-demographic characteristics and the clinical and reproductive history of women. A total of 100,332 pregnant women were eligible for the analysis. Of these, 2003 (2.0%) received the A/H1N1 pandemic influenza vaccination during the second or third trimester of gestation. We did not observe any statistically significant association between the A/H1N1 pandemic influenza vaccination and different maternal outcomes (hospital admissions for influenza, pneumonia, hypertension, eclampsia, diabetes, thyroid disease, and anaemia), fetal outcomes (fetal death after the 22nd gestational week) and neonatal outcomes (pre-term birth, low birth weight, low 5-min Apgar score, and congenital malformations). Pre-existing health-risk conditions (hospital admissions and drug prescriptions for specific diseases before the onset of pregnancy) were observed more frequently among vaccinated women, thus suggesting that concomitant chronic conditions increased vaccination uptake. The results of this study add some evidence on the safety of A/H1N1 pandemic influenza vaccination during

  14. Immunogenicity and tolerability after two doses of non-adjuvanted, whole-virion pandemic influenza A (H1N1) vaccine in HIV-infected individuals.

    PubMed

    Lagler, Heimo; Grabmeier-Pfistershammer, Katharina; Touzeau-Römer, Veronique; Tobudic, Selma; Ramharter, Michael; Wenisch, Judith; Gualdoni, Guido Andrés; Redlberger-Fritz, Monika; Popow-Kraupp, Theresia; Rieger, Armin; Burgmann, Heinz

    2012-01-01

    During the influenza pandemic of 2009/10, the whole-virion, Vero-cell-derived, inactivated, pandemic influenza A (H1N1) vaccine Celvapan® (Baxter) was used in Austria. Celvapan® is adjuvant-free and was the only such vaccine at that time in Europe. The objective of this observational, non-interventional, prospective single-center study was to evaluate the immunogenicity and tolerability of two intramuscular doses of this novel vaccine in HIV-positive individuals. A standard hemagglutination inhibition (HAI) assay was used for evaluation of the seroconversion rate and seroprotection against the pandemic H1N1 strain. In addition, H1N1-specific IgG antibodies were measured using a recently developed ELISA and compared with the HAI results. Tolerability of vaccination was evaluated up to one month after the second dose. A total of 79 HIV-infected adults with an indication for H1N1 vaccination were evaluated. At baseline, 55 of the 79 participants had an HAI titer ≥1:40 and two patients showed a positive IgG ELISA. The seroconversion rate was 31% after the first vaccination, increasing to 41% after the second; the corresponding seroprotection rates were 92% and 83% respectively. ELISA IgG levels were positive in 25% after the first vaccination and in 37% after the second. Among the participants with baseline HAI titers <1:40, 63% seroconverted. Young age was clearly associated with lower HAI titers at baseline and with higher seroconversion rates, whereas none of the seven patients >60 years of age had a baseline HAI titer <1:40 or seroconverted after vaccination. The vaccine was well tolerated. The non-adjuvanted pandemic influenza A (H1N1) vaccine was well tolerated and induced a measurable immune response in a sample of HIV-infected individuals.

  15. Immunogenicity and Tolerability after Two Doses of Non-Adjuvanted, Whole-Virion Pandemic Influenza A (H1N1) Vaccine in HIV-Infected Individuals

    PubMed Central

    Lagler, Heimo; Grabmeier-Pfistershammer, Katharina; Touzeau-Römer, Veronique; Tobudic, Selma; Ramharter, Michael; Wenisch, Judith; Gualdoni, Guido Andrés; Redlberger-Fritz, Monika; Popow-Kraupp, Theresia; Rieger, Armin; Burgmann, Heinz

    2012-01-01

    Background During the influenza pandemic of 2009/10, the whole-virion, Vero-cell-derived, inactivated, pandemic influenza A (H1N1) vaccine Celvapan® (Baxter) was used in Austria. Celvapan® is adjuvant-free and was the only such vaccine at that time in Europe. The objective of this observational, non-interventional, prospective single-center study was to evaluate the immunogenicity and tolerability of two intramuscular doses of this novel vaccine in HIV-positive individuals. Methods and Findings A standard hemagglutination inhibition (HAI) assay was used for evaluation of the seroconversion rate and seroprotection against the pandemic H1N1 strain. In addition, H1N1-specific IgG antibodies were measured using a recently developed ELISA and compared with the HAI results. Tolerability of vaccination was evaluated up to one month after the second dose. A total of 79 HIV-infected adults with an indication for H1N1 vaccination were evaluated. At baseline, 55 of the 79 participants had an HAI titer ≥1∶40 and two patients showed a positive IgG ELISA. The seroconversion rate was 31% after the first vaccination, increasing to 41% after the second; the corresponding seroprotection rates were 92% and 83% respectively. ELISA IgG levels were positive in 25% after the first vaccination and in 37% after the second. Among the participants with baseline HAI titers <1∶40, 63% seroconverted. Young age was clearly associated with lower HAI titers at baseline and with higher seroconversion rates, whereas none of the seven patients >60 years of age had a baseline HAI titer <1∶40 or seroconverted after vaccination. The vaccine was well tolerated. Conclusion The non-adjuvanted pandemic influenza A (H1N1) vaccine was well tolerated and induced a measurable immune response in a sample of HIV-infected individuals. PMID:22629330

  16. Emergence of H5N1 high pathogenicity avian influenza strains in Indonesia that are resistant to vaccines

    USDA-ARS?s Scientific Manuscript database

    Vaccines have been used to protect poultry in Asia against H5N1 high pathogenicity avian influenza (HPAI) since 2002. Reports of vaccine “failures” began to emerge in 2006 in Indonesia, with identification of clinical disease consistent with HPAI or isolation of H5N1 HPAIV in vaccinated flocks or in...

  17. Safety and immunogenicity of 2010-2011 H1N12009-containing trivalent inactivated influenza vaccine in children 12-59 months of age previously given AS03-adjuvanted H1N12009 pandemic vaccine: a PHAC/CIHR Influenza Research Network (PCIRN) study.

    PubMed

    Langley, Joanne M; Scheifele, David W; Quach, Caroline; Vanderkooi, Otto G; Ward, Brian; McNeil, Shelly; Dobson, Simon; Kellner, James D; Kuhn, Susan; Kollman, Tobias; MacKinnon-Cameron, Donna; Smith, Bruce; Li, Yan; Halperin, Scott A

    2012-05-14

    Concern arose in 2010 that reactogenicity, particularly febrile seizures, to influenza A/H1N1-containing 2010-2011 trivalent seasonal inactivated influenza vaccine (TIV) could occur in young children who had been previously immunized and/or infected with the pandemic strain. We conducted a pre-season study of 2010-2011 TIV safety and immunogenicity in children 12-59 months of age to inform public health decision making. Children immunized with 1 or 2 doses of the pandemic vaccine, with or without the 2009-10 TIV, received 1 or 2 doses of 2010-11 TIV in an observational, multicentre Canadian study. Standard safety monitoring was enhanced by a telephone call at ~24 h post-TIV when adverse events were expected to peak. Summary safety reports were rapidly reported to public health before the launch of public programs. TIV immunogenicity was assessed day 0, and 21 days after final vaccination. Clinical Trials Registration NCT01180621. Among 207 children, a general adverse event was reported by 60.9% of children post-dose one and by 58.3% post-dose two. Only severe fever (>38.5°C) was more common in two-dose compared to one dose recipients (16.7%, n=4 v. 1.0%, n=2). At baseline 99.0% of participants had A/H1N1 hemagglutinin inhibition (HAI) titers ≥10, and 85.5% had a protective titer of ≥40 (95% CI 80.0, 90.0). Baseline geometric mean titers (GMT) were higher in recipients of a 2-dose schedule of pandemic vaccine compared to one-dose recipients: 153.1 (95% CI 126.2, 185.7) v. 78.8 ((58.1, 106.8, p<0.001). At 21 days, all regulatory criteria for influenza vaccine immunogenicity were exceeded for A/H1N1 and H3N2, but responses to the B antigen were poor. No correlations between reactogenicity and either baseline high influenza titers or serologic response to revaccination were evident. Infants and toddlers who received AS03-adjuvanted A/H1N1 2009 vaccine up to 11 months earlier retained high titers in the subsequent season but re-exposure to A/H1N1 2009 antigen in

  18. Comparison of the efficacy of a commercial inactivated influenza A/H1N1/pdm09 virus (pH1N1) vaccine and two experimental M2e-based vaccines against pH1N1 challenge in the growing pig model.

    PubMed

    Opriessnig, Tanja; Gauger, Phillip C; Gerber, Priscilla F; Castro, Alessandra M M G; Shen, Huigang; Murphy, Lita; Digard, Paul; Halbur, Patrick G; Xia, Ming; Jiang, Xi; Tan, Ming

    2018-01-01

    Swine influenza A viruses (IAV-S) found in North American pigs are diverse and the lack of cross-protection among heterologous strains is a concern. The objective of this study was to compare a commercial inactivated A/H1N1/pdm09 (pH1N1) vaccine and two novel subunit vaccines, using IAV M2 ectodomain (M2e) epitopes as antigens, in a growing pig model. Thirty-nine 2-week-old IAV negative pigs were randomly assigned to five groups and rooms. At 3 weeks of age and again at 5 weeks of age, pigs were vaccinated intranasally with an experimental subunit particle vaccine (NvParticle/M2e) or a subunit complex-based vaccine (NvComplex/M2e) or intramuscularly with a commercial inactivated vaccine (Inact/pH1N1). At 7 weeks of age, the pigs were challenged with pH1N1 virus or sham-inoculated. Necropsy was conducted 5 days post pH1N1 challenge (dpc). At the time of challenge one of the Inact/pH1N1 pigs had seroconverted based on IAV nucleoprotein-based ELISA, Inact/pH1N1 pigs had significantly higher pdm09H1N1 hemagglutination inhibition (HI) titers compared to all other groups, and M2e-specific IgG responses were detected in the NvParticle/M2e and the NvComplex/M2e pigs with significantly higher group means in the NvComplex/M2e group compared to SHAMVAC-NEG pigs. After challenge, nasal IAV RNA shedding was significantly reduced in Inact/pH1N1 pigs compared to all other pH1N1 infected groups and this group also had reduced IAV RNA in oral fluids. The macroscopic lung lesions were characterized by mild-to-severe, multifocal-to-diffuse, cranioventral dark purple consolidated areas typical of IAV infection and were similar for NvParticle/M2e, NvComplex/M2e and SHAMVAC-IAV pigs. Lesions were significantly less severe in the SHAMVAC-NEG and the Inact/pH1N1pigs. Under the conditions of this study, a commercial Inact/pH1N1 specific vaccine effectively protected pigs against homologous challenge as evidenced by reduced clinical signs, virus shedding in nasal secretions and oral fluids

  19. Comparison of the efficacy of a commercial inactivated influenza A/H1N1/pdm09 virus (pH1N1) vaccine and two experimental M2e-based vaccines against pH1N1 challenge in the growing pig model

    PubMed Central

    Gauger, Phillip C.; Gerber, Priscilla F.; Castro, Alessandra M. M. G.; Shen, Huigang; Murphy, Lita; Digard, Paul; Halbur, Patrick G.; Xia, Ming; Jiang, Xi; Tan, Ming

    2018-01-01

    Swine influenza A viruses (IAV-S) found in North American pigs are diverse and the lack of cross-protection among heterologous strains is a concern. The objective of this study was to compare a commercial inactivated A/H1N1/pdm09 (pH1N1) vaccine and two novel subunit vaccines, using IAV M2 ectodomain (M2e) epitopes as antigens, in a growing pig model. Thirty-nine 2-week-old IAV negative pigs were randomly assigned to five groups and rooms. At 3 weeks of age and again at 5 weeks of age, pigs were vaccinated intranasally with an experimental subunit particle vaccine (NvParticle/M2e) or a subunit complex-based vaccine (NvComplex/M2e) or intramuscularly with a commercial inactivated vaccine (Inact/pH1N1). At 7 weeks of age, the pigs were challenged with pH1N1 virus or sham-inoculated. Necropsy was conducted 5 days post pH1N1 challenge (dpc). At the time of challenge one of the Inact/pH1N1 pigs had seroconverted based on IAV nucleoprotein-based ELISA, Inact/pH1N1 pigs had significantly higher pdm09H1N1 hemagglutination inhibition (HI) titers compared to all other groups, and M2e-specific IgG responses were detected in the NvParticle/M2e and the NvComplex/M2e pigs with significantly higher group means in the NvComplex/M2e group compared to SHAMVAC-NEG pigs. After challenge, nasal IAV RNA shedding was significantly reduced in Inact/pH1N1 pigs compared to all other pH1N1 infected groups and this group also had reduced IAV RNA in oral fluids. The macroscopic lung lesions were characterized by mild-to-severe, multifocal-to-diffuse, cranioventral dark purple consolidated areas typical of IAV infection and were similar for NvParticle/M2e, NvComplex/M2e and SHAMVAC-IAV pigs. Lesions were significantly less severe in the SHAMVAC-NEG and the Inact/pH1N1pigs. Under the conditions of this study, a commercial Inact/pH1N1 specific vaccine effectively protected pigs against homologous challenge as evidenced by reduced clinical signs, virus shedding in nasal secretions and oral fluids

  20. 2015/16 I-MOVE/I-MOVE+ multicentre case-control study in Europe: Moderate vaccine effectiveness estimates against influenza A(H1N1)pdm09 and low estimates against lineage-mismatched influenza B among children.

    PubMed

    Kissling, Esther; Valenciano, Marta; Pozo, Francisco; Vilcu, Ana-Maria; Reuss, Annicka; Rizzo, Caterina; Larrauri, Amparo; Horváth, Judit Krisztina; Brytting, Mia; Domegan, Lisa; Korczyńska, Monika; Meijer, Adam; Machado, Ausenda; Ivanciuc, Alina; Višekruna Vučina, Vesna; van der Werf, Sylvie; Schweiger, Brunhilde; Bella, Antonino; Gherasim, Alin; Ferenczi, Annamária; Zakikhany, Katherina; O Donnell, Joan; Paradowska-Stankiewicz, Iwona; Dijkstra, Frederika; Guiomar, Raquel; Lazar, Mihaela; Kurečić Filipović, Sanja; Johansen, Kari; Moren, Alain

    2018-07-01

    During the 2015/16 influenza season in Europe, the cocirculating influenza viruses were A(H1N1)pdm09 and B/Victoria, which was antigenically distinct from the B/Yamagata component in the trivalent influenza vaccine. We used the test-negative design in a multicentre case-control study in twelve European countries to measure 2015/16 influenza vaccine effectiveness (VE) against medically attended influenza-like illness (ILI) laboratory-confirmed as influenza. General practitioners swabbed a systematic sample of consulting ILI patients and a random sample of influenza-positive swabs was sequenced. We calculated adjusted VE against influenza A(H1N1)pdm09, A(H1N1)pdm09 genetic group 6B.1 and influenza B overall and by age group. We included 11 430 ILI patients, of which 2272 were influenza A(H1N1)pdm09 and 2901 were influenza B cases. Overall VE against influenza A(H1N1)pdm09 was 32.9% (95% CI: 15.5-46.7). Among those aged 0-14, 15-64 and ≥65 years, VE against A(H1N1)pdm09 was 31.9% (95% CI: -32.3 to 65.0), 41.4% (95% CI: 20.5-56.7) and 13.2% (95% CI: -38.0 to 45.3), respectively. Overall VE against influenza A(H1N1)pdm09 genetic group 6B.1 was 32.8% (95% CI: -4.1 to 56.7). Among those aged 0-14, 15-64 and ≥65 years, VE against influenza B was -47.6% (95% CI: -124.9 to 3.1), 27.3% (95% CI: -4.6 to 49.4) and 9.3% (95% CI: -44.1 to 42.9), respectively. Vaccine effectiveness (VE) against influenza A(H1N1)pdm09 and its genetic group 6B.1 was moderate in children and adults, and low among individuals ≥65 years. Vaccine effectiveness (VE) against influenza B was low and heterogeneous among age groups. More information on effects of previous vaccination and previous infection is needed to understand the VE results against influenza B in the context of a mismatched vaccine. © 2017 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.

  1. Avian Influenza A(H5N1) Virus in Egypt.

    PubMed

    Kayali, Ghazi; Kandeil, Ahmed; El-Shesheny, Rabeh; Kayed, Ahmed S; Maatouq, Asmaa M; Cai, Zhipeng; McKenzie, Pamela P; Webby, Richard J; El Refaey, Samir; Kandeel, Amr; Ali, Mohamed A

    2016-03-01

    In Egypt, avian influenza A subtype H5N1 and H9N2 viruses are enzootic in poultry. The control plan devised by veterinary authorities in Egypt to prevent infections in poultry focused mainly on vaccination and ultimately failed. Recently, widespread H5N1 infections in poultry and a substantial increase in the number of human cases of H5N1 infection were observed. We summarize surveillance data from 2009 through 2014 and show that avian influenza viruses are established in poultry in Egypt and are continuously evolving genetically and antigenically. We also discuss the epidemiology of human infection with avian influenza in Egypt and describe how the true burden of disease is underestimated. We discuss the failures of relying on vaccinating poultry as the sole intervention tool. We conclude by highlighting the key components that need to be included in a new strategy to control avian influenza infections in poultry and humans in Egypt.

  2. Avian Influenza A(H5N1) Virus in Egypt

    PubMed Central

    Kandeil, Ahmed; El-Shesheny, Rabeh; Kayed, Ahmed S.; Maatouq, Asmaa M.; Cai, Zhipeng; McKenzie, Pamela P.; Webby, Richard J.; El Refaey, Samir; Kandeel, Amr; Ali, Mohamed A.

    2016-01-01

    In Egypt, avian influenza A subtype H5N1 and H9N2 viruses are enzootic in poultry. The control plan devised by veterinary authorities in Egypt to prevent infections in poultry focused mainly on vaccination and ultimately failed. Recently, widespread H5N1 infections in poultry and a substantial increase in the number of human cases of H5N1 infection were observed. We summarize surveillance data from 2009 through 2014 and show that avian influenza viruses are established in poultry in Egypt and are continuously evolving genetically and antigenically. We also discuss the epidemiology of human infection with avian influenza in Egypt and describe how the true burden of disease is underestimated. We discuss the failures of relying on vaccinating poultry as the sole intervention tool. We conclude by highlighting the key components that need to be included in a new strategy to control avian influenza infections in poultry and humans in Egypt. PMID:26886164

  3. Profiles of influenza A/H1N1 vaccine response using hemagglutination-inhibition titers.

    PubMed

    Jacobson, Robert M; Grill, Diane E; Oberg, Ann L; Tosh, Pritish K; Ovsyannikova, Inna G; Poland, Gregory A

    2015-01-01

    To identify distinct antibody profiles among adults 50-to-74 years old using influenza A/H1N1 HI titers up to 75 days after vaccination. Healthy subjects 50 to 74 years old received the 2010-2011 trivalent inactivated influenza vaccine. We measured venous samples from Days 0, 28, and 75 for HI and VNA and B-cell ELISPOTs. Of 106 subjects, HI titers demonstrated a ceiling effect for 11 or 10% for those with a pre-vaccination HI titer of 1:640 where no subject post-vaccination had an increase in titer. Of the remaining 95 subjects, only 37 or 35% overall had at least a 4-fold increase by Day 28. Of these 37, 3 waned at least 4-fold, and 13 others 2-fold. Thus 15% of the subjects showed waning antibody titers by Day 75. More than half failed to respond at all. The profiles populated by these subjects as defined by HI did not vary with age or gender. The VNA results mimicked the HI profiles, but the profiles for B-cell ELISPOT did not. HI titers at Days 0, 28, and 75 populate 4 biologically plausible profiles. Limitations include lack of consensus for operationally defining waning as well as for the apparent ceiling. Furthermore, though well accepted as a marker for vaccine response, assigning thresholds with HI has limitations. However, VNA closely matches HI in populating these profiles. Thus, we hold that these profiles, having face- and content-validity, may provide a basis for understanding variation in genomic and transcriptomic response to influenza vaccination in this age group.

  4. Pandemic influenza A H1N1 vaccine in recipients of solid organ transplants: immunogenicity and tolerability outcomes after vero cell derived, non-adjuvanted, whole-virion vaccination.

    PubMed

    Lagler, Heimo; Wenisch, Judith M; Tobudic, Selma; Gualdoni, Guido A; Rödler, Susanne; Rasoul-Rockenschaub, Susanne; Jaksch, Peter; Redlberger-Fritz, Monika; Popow-Kraupp, Theresia; Burgmann, Heinz

    2011-09-16

    During the 2009/10 pandemic of influenza A (H1N1), the American Society of Transplantation and other health organizations recommended that immunocompromised patients should be vaccinated as the key preventive measure. Since there are no data available for the immunogenicity of the unadjuvanted pandemic influenza vaccine in immunocompromised patients - as opposed to the adjuvanted preparation - the objective of this study was to evaluate the immunogenicity of an adjuvant-free H1N1 vaccine in recipients of solid organ transplants. Patients were recruited at the Vienna General Hospital, Austria. The vaccination schedule consisted of 2 doses of a whole-virion, vero cell derived, inactivated, non-adjuvanted influenza A/California/07/2009 (H1N1) vaccine given with an interval of 3 weeks. A hemagglutination inhibition (HI) assay on blood samples obtained prior to the first and after each vaccination was used for serologic analysis. The primary immunologic endpoint was the seroconversion rate, defined as the proportion of subjects with an individual 4-fold increase in HI titer of at least 1:40. In addition, virus-specific IgG antibodies to the pandemic H1N1 strain were measured using a commercially available ELISA. Twenty-five organ transplant patients (16 males, 9 females) aged 25-79 years were vaccinated and provided blood samples for serologic analysis. The time elapsed since transplantation was 10 months to 25 years (mean: 9 years; 95% CI 6-13 years). The vaccine was well tolerated and no local adverse events were noticed. After two vaccinations 37% of the patients demonstrated seroconversion in the HI assay as defined above and 70% had virus-specific IgG antibodies. Among the HI vaccine responders were 6 of 14 heart transplant recipients and 1 of 4 liver transplant recipients. The number and type of immunosuppressive agents did not significantly differ in their effect on the immune response. Our results show that the novel vero cell derived and adjuvant-free pandemic

  5. Guillain-Barré Syndrome and Adjuvanted Pandemic Influenza A (H1N1) 2009 Vaccines: A Multinational Self-Controlled Case Series in Europe

    PubMed Central

    Dieleman, Jeanne P.; Olberg, Henning K.; de Vries, Corinne S.; Sammon, Cormac; Andrews, Nick; Svanström, Henrik; Mølgaard-Nielsen, Ditte; Hviid, Anders; Lapeyre-Mestre, Maryse; Sommet, Agnès; Saussier, Christel; Castot, Anne; Heijbel, Harald; Arnheim-Dahlström, Lisen; Sparen, Par; Mosseveld, Mees; Schuemie, Martijn; van der Maas, Nicoline; Jacobs, Bart C.; Leino, Tuija; Kilpi, Terhi; Storsaeter, Jann; Johansen, Kari; Kramarz, Piotr; Bonhoeffer, Jan; Sturkenboom, Miriam C. J. M.

    2014-01-01

    Background The risk of Guillain-Barré syndrome (GBS) following the United States' 1976 swine flu vaccination campaign in the USA led to enhanced active surveillance during the pandemic influenza (A(H1N1)pdm09) immunization campaign. This study aimed to estimate the risk of GBS following influenza A(H1N1)pdm09 vaccination. Methods A self-controlled case series (SCCS) analysis was performed in Denmark, Finland, France, Netherlands, Norway, Sweden, and the United Kingdom. Information was collected according to a common protocol and standardised procedures. Cases classified at levels 1–4a of the Brighton Collaboration case definition were included. The risk window was 42 days starting the day after vaccination. Conditional Poisson regression and pooled random effects models estimated adjusted relative incidences (RI). Pseudo likelihood and vaccinated-only methods addressed the potential contraindication for vaccination following GBS. Results Three hundred and three (303) GBS and Miller Fisher syndrome cases were included. Ninety-nine (99) were exposed to A(H1N1)pdm09 vaccination, which was most frequently adjuvanted (Pandemrix and Focetria). The unadjusted pooled RI for A(H1N1)pdm09 vaccination and GBS was 3.5 (95% Confidence Interval (CI): 2.2–5.5), based on all countries. This lowered to 2.0 (95% CI: 1.2–3.1) after adjustment for calendartime and to 1.9 (95% CI: 1.1–3.2) when we accounted for contra-indications. In a subset (Netherlands, Norway, and United Kingdom) we further adjusted for other confounders and there the RI decreased from 1.7 (adjusted for calendar month) to 1.4 (95% CI: 0.7–2.8), which is the main finding. Conclusion This study illustrates the potential of conducting European collaborative vaccine safety studies. The main, fully adjusted analysis, showed that the RI of GBS was not significantly elevated after influenza A(H1N1)pdm09 vaccination (RI = 1.4 (95% CI: 0.7–2.8). Based on the upper limits of the pooled estimate we can rule

  6. Febrile seizures after 2009 influenza A (H1N1) vaccination and infection: a nationwide registry-based study.

    PubMed

    Bakken, Inger Johanne; Aaberg, Kari Modalsli; Ghaderi, Sara; Gunnes, Nina; Trogstad, Lill; Magnus, Per; Håberg, Siri Eldevik

    2015-11-09

    During the 2009 influenza A (H1N1) pandemic, a monovalent pandemic strain vaccine containing the oil-in-water adjuvant AS03 (Pandemrix®) was offered to the Norwegian population. The coverage among children reached 54%. Our aim was to estimate the risk of febrile seizure in children after exposure to pandemic influenza vaccination or infection. The study population comprised 226,889 children born 2006-2009 resident in Norway per October 1st, 2009. Febrile seizure episodes were defined by emergency hospital admissions / emergency outpatient hospital care with International Classification of Diseases, Version 10, codes R56.0 or R56.8. The self-controlled case series method was applied to estimate incidence rate ratios (IRRs) in pre-defined risk periods compared to the background period. The total observation window was ± 180 days from exposure day. Among 113,068 vaccinated children, 656 (0.6%) had at least one febrile seizure episode. The IRR of febrile seizures 1-3 days after vaccination was 2.00 (95% confidence interval [CI]: 1.15-3.51). In the period 4-7 days after vaccination, no increased risk was observed. Among the 8172 children diagnosed with pandemic influenza, 84 (1.0%) had at least one febrile seizure episode. The IRR of febrile seizures on the same day as a diagnosis of influenza was 116.70 (95% CI: 62.81-216.90). In the period 1-3 days after a diagnosis of influenza, a tenfold increased risk was observed (IRR 10.12, 95% CI: 3.82 - 26.82). In this large population-based study with precise timing of exposures and outcomes, we found a twofold increased risk of febrile seizures 1-3 days after pandemic influenza vaccination. However, we found that pandemic influenza infection was associated with a much stronger increase in risk of febrile seizures.

  7. Sequential Seasonal H1N1 Influenza Virus Infections Protect Ferrets against Novel 2009 H1N1 Influenza Virus

    PubMed Central

    Carter, Donald M.; Bloom, Chalise E.; Nascimento, Eduardo J. M.; Marques, Ernesto T. A.; Craigo, Jodi K.; Cherry, Joshua L.; Lipman, David J.

    2013-01-01

    Individuals <60 years of age had the lowest incidence of infection, with ∼25% of these people having preexisting, cross-reactive antibodies to novel 2009 H1N1 influenza. Many people >60 years old also had preexisting antibodies to novel H1N1. These observations are puzzling because the seasonal H1N1 viruses circulating during the last 60 years were not antigenically similar to novel H1N1. We therefore hypothesized that a sequence of exposures to antigenically different seasonal H1N1 viruses can elicit an antibody response that protects against novel 2009 H1N1. Ferrets were preinfected with seasonal H1N1 viruses and assessed for cross-reactive antibodies to novel H1N1. Serum from infected ferrets was assayed for cross-reactivity to both seasonal and novel 2009 H1N1 strains. These results were compared to those of ferrets that were sequentially infected with H1N1 viruses isolated prior to 1957 or more-recently isolated viruses. Following seroconversion, ferrets were challenged with novel H1N1 influenza virus and assessed for viral titers in the nasal wash, morbidity, and mortality. There was no hemagglutination inhibition (HAI) cross-reactivity in ferrets infected with any single seasonal H1N1 influenza viruses, with limited protection to challenge. However, sequential H1N1 influenza infections reduced the incidence of disease and elicited cross-reactive antibodies to novel H1N1 isolates. The amount and duration of virus shedding and the frequency of transmission following novel H1N1 challenge were reduced. Exposure to multiple seasonal H1N1 influenza viruses, and not to any single H1N1 influenza virus, elicits a breadth of antibodies that neutralize novel H1N1 even though the host was never exposed to the novel H1N1 influenza viruses. PMID:23115287

  8. The Influenza Virus and the 2009 H1N1 Outbreak

    DTIC Science & Technology

    2016-04-08

    Envelope L’ol • Sequencing Figure 1 Influenza Virus Anatomy -Neuramlnldase (Sialldase) ’ Hemagglutlnln 9 Key laboratory techniques...discover the 2009 H1 N1 influenza virus Phylogenetic Tree Out of the over 400 human H1 ’s USAFSAM sequenced this season no specimen has had less than a...surveillance/vaccine contents • Shot Versus Flu Mist • How does Tamiflu work • Sequencing HA - Culture, HAI, PCR, Serology ••• • t.tt

  9. Asymptomatic ratio for seasonal H1N1 influenza infection among schoolchildren in Taiwan.

    PubMed

    Hsieh, Ying-Hen; Tsai, Chen-An; Lin, Chien-Yu; Chen, Jin-Hua; King, Chwan-Chuen; Chao, Day-Yu; Cheng, Kuang-Fu

    2014-02-12

    Studies indicate that asymptomatic infections do indeed occur frequently for both seasonal and pandemic influenza, accounting for about one-third of influenza infections. Studies carried out during the 2009 pH1N1 pandemic have found significant antibody response against seasonal H1N1 and H3N2 vaccine strains in schoolchildren receiving only pandemic H1N1 monovalent vaccine, yet reported either no symptoms or only mild symptoms. Serum samples of 255 schoolchildren, who had not received vaccination and had pre-season HI Ab serotiters <40, were collected from urban, rural areas and an isolated island in Taiwan during the 2005-2006 influenza season. Their hemagglutination inhibition antibody (HI Ab) serotiters against the 2005 A/New Caledonia/20/99 (H1N1) vaccine strain at pre-season and post-season were measured to determine the symptoms with the highest correlation with infection, as defined by 4-fold rise in HI titer. We estimate the asymptomatic ratio, or the proportion of asymptomatic infections, for schoolchildren during the 2005-6 influenza season when this vaccine strain was found to be antigenically related to the circulating H1N1 strain. Fever has the highest correlation with the 2005-06 seasonal influenza A(H1N1) infection, followed by headache, cough, vomiting, and sore throat. Asymptomatic ratio for the schoolchildren is found to range between 55.6% (95% CI: 44.7-66.4)-77.9% (68.8-87.0) using different sets of predictive symptoms. Moreover, the asymptomatic ratio was 66.9% (56.6-77.2) when using US-CDC criterion of fever + (cough/sore throat), and 73.0 (63.3-82.8) when under Taiwan CDC definition of Fever + (cough or sore throat or nose) + ( headache or pain or fatigue). Asymptomatic ratio for children is found to be substantially higher than that of the general population in literature. In providing reasonable quantification of the asymptomatic infected children spreading pathogens to others in a seasonal epidemic or a pandemic, our estimates

  10. [Attitudes and side effects related to pandemic influenza A (H1N1) vaccination in healthcare personnel].

    PubMed

    Ormen, Bahar; Türker, Nesrin; Vardar, Ilknur; Kaptan, Figen; El, Sibel; Ural, Serap; Kaya, Fatih; Coşkun, Nejat Ali

    2012-01-01

    The aims of this study were to evaluate the attitudes towards H1N1 vaccination and to determine the safety and side effects following 2009 pandemic influenza A (H1N1) vaccination. Pandemic influenza vaccine had been administered to the healthcare personnel in our research and training hospital in December 2009. The rate being vaccinated was established as 40% (800/2000). Four months following vaccination, the opinions about vaccination were asked to the healthcare workers, and also side effects were questioned to the vaccinated group. Two different questionnaires (for vaccinated and unvaccinated subjects) were delivered to the volunteers who agreed to participate in the study. Demographic features, reasons related to being vaccinated or not, were questioned. The vaccinated group was also questioned for the presence of chronic diseases, previous vaccinations (pandemic/seasonal influenza), local or systemic reactions that develop after vaccination. A total of 332 volunteers participated in the questionnaire. Of them 247 (74.4%) were vaccinated and 85 (25.6%) were unvaccinated. Male/female ratio of the participants was 1.2, and 55.7% of them were older than 30-year-old. Most of the participants (82.8%) were highly educated (high school and faculty-graduated). Vaccination rates were found statistically significant in advanced age group compared to young adults (p= 0.042); in male gender compared to females (p= 0.001) and in parents compared to subjects who didn't have children (p= 0.021). Vaccination rates were observed to be higher (57.5%) in non-medical staff (cleaning employers, administrative personnel, etc.) than the physicians (29.1%) and nurses (13.4%), and the rate was also high (54.7%) in personnel who worked in intensive care units, emergency department and administrative units than the personnel who worked in the clinics of internal medicine (22.3%) and surgery (23.1%) (p= 0.001). The most important causes of rejecting vaccination were being afraid of the

  11. Continued dominance of pandemic A(H1N1) 2009 influenza in Victoria, Australia in 2010

    PubMed Central

    Grant, Kristina; Franklin, Lucinda; Kaczmarek, Marlena; Hurt, Aeron; Kostecki, Renata; Kelly, Heath

    2011-01-01

    The 2010 Victorian influenza season was characterized by normal seasonal influenza activity and the dominance of the pandemic A(H1N1) 2009 strain. General Practice Sentinel Surveillance rates peaked at 9.4 ILI cases per 1000 consultations in week 36 for metropolitan practices, and at 10.5 ILI cases per 1000 in the following week for rural practices. Of the 678 ILI cases, 23% were vaccinated, a significantly higher percentage than in previous years. A significantly higher percentage of ILI patients were swabbed in 2010 compared to 2003–2008, but similar to 2009, with a similar percentage being positive for influenza as in previous years. Vaccination rates increased with patient age. Melbourne Medical Deputising Service rates peaked in week 35 at 19.1 ILI cases per 1000 consultations. Of the 1914 cases of influenza notified to the Department of Health, Victoria, 1812 (95%) were influenza A infections – 1001 (55%) pandemic A(H1N1) 2009, 4 (< 1%) A(H3N2) and 807 (45%) not subtyped; 88 (5%) were influenza B; and 14 (< 1%) were influenza A and B co-infections. The World Health Organization Collaborating Centre for Reference and Research on Influenza tested 403 isolates of which 261 were positive for influenza, 250 of which were influenza A and 11 were influenza B. Ninety-two per cent of the influenza A viruses were pandemic A(H1N1) 2009, and following antigenic analysis all of these were found to be similar to the current vaccine strain. Three viruses (0.9%) were found to be oseltamivir resistant due to an H275Y mutation in the neuraminidase gene. PMID:23908889

  12. The priming effect of previous natural pandemic H1N1 infection on the immunogenicity to subsequent 2010-2011 influenza vaccination in children: a prospective cohort study.

    PubMed

    Kang, Eun Kyeong; Eun, Byung Wook; Kim, Nam Hee; Lim, Jung Sub; Lee, Jun Ah; Kim, Dong Ho

    2016-08-22

    The effect of previous natural pandemic H1N1 (H1N1 pdm09) influenza infection on the immunogenicity to subsequent inactivated influenza vaccination in children has not been well studied. We aimed to evaluate the effect of H1N1 pdm09 natural infection and vaccination on the immunogenicity to subsequent 2010-2011 seasonal inactivated influenza vaccination in children. From October 2010 to May 2011, we conducted an open-label, multi-center study in children aged 6 months -18 years in Korea. We measured antibody titers with a hemagglutination-inhibition (HI) assay at baseline, 1 month, and 6 months after vaccination with trivalent split or subunit vaccines containing H1N1 pdm, A/H3N2, and B. The subjects were classified into 4 groups depending on the presence of laboratory-confirmed H1N1 pdm09 infection and/or vaccination in the 2009-2010 season; Group I: vaccination (-)/infection(-), Group II: vaccination (-)/infection(+), Group III: vaccination (+)/infection(-), Group IV: vaccination (+)/infection(+). Among the subjects in group I, 47 subjects who had a baseline titer >1:10 were considered to have an asymptomatic infection. They were included into the final group II (n = 80). We defined the new group II as the infection-primed (IP) group and group III as the vaccine-primed (VP) group. Seroconversion rate (57.5 % vs 35.9 %, p = 0.001), seroprotection rate at 6 months after vaccination (70.8 % vs 61.8 %, p = 0.032), and GMT at 1 month after vaccination (129.9 vs 66.5, p = 0.002) were significantly higher in the IP group than in the VP group. In the 9-18 year-old group, seroconversion rate and immunogenicity at 1 and 6 months were significantly higher in the IP group than in the VP group. However in the 1-7 year-old age group, there was no significant difference between the two groups. Previous H1N1 pdm09 infection appears to have positive effects on immunogenicity of subsequent inactivated influenza vaccines against H1N1 pdm09 in older

  13. Protection of guinea pigs by vaccination with a recombinant swinepox virus co-expressing HA1 genes of swine H1N1 and H3N2 influenza viruses.

    PubMed

    Xu, Jiarong; Yang, Deji; Huang, Dongyan; Xu, Jiaping; Liu, Shichao; Lin, Huixing; Zhu, Haodan; Liu, Bao; Lu, Chengping

    2013-03-01

    Swine influenza (SI) is an acute respiratory infectious disease of swine caused by swine influenza virus (SIV). SIV is not only an important respiratory pathogen in pigs but also a potent threat to human health. Here, we report the construction of a recombinant swinepox virus (rSPV/H3-2A-H1) co-expressing hemagglutinin (HA1) of SIV subtypes H1N1 and H3N2. Immune responses and protection efficacy of the rSPV/H3-2A-H1 were evaluated in guinea pigs. Inoculation of rSPV/H3-2A-H1 yielded neutralizing antibodies against SIV H1N1 and H3N2. The IFN-γ and IL-4 concentrations in the supernatant of lymphocytes stimulated with purified SIV HA1 antigen were significantly higher (P < 0.01) than those of the control groups. Complete protection of guinea pigs against SIV H1N1 or H3N2 challenge was observed. No SIV shedding was detected from guinea pigs vaccinated with rSPV/H3-2A-H1 after challenge. Most importantly, the guinea pigs immunized with rSPV/H3-2A-H1 did not show gross and micrographic lung lesions. However, the control guinea pigs experienced distinct gross and micrographic lung lesions at 7 days post-challenge. Our data suggest that the recombinant swinepox virus encoding HA1 of SIV H1N1 and H3N2 might serve as a promising candidate vaccine for protection against SIV H1N1 and H3N2 infections.

  14. The Contribution of Systemic and Pulmonary Immune Effectors to Vaccine-Induced Protection from H5N1 Influenza Virus Infection

    PubMed Central

    Lau, Yuk-Fai; Wright, Amber R.

    2012-01-01

    Live attenuated influenza vaccines (LAIVs) are effective in providing protection against influenza challenge in animal models and in preventing disease in humans. We previously showed that LAIVs elicit a range of immune effectors and that successful induction of pulmonary cellular and humoral immunity in mice requires pulmonary replication of the vaccine virus. An upper respiratory tract immunization (URTI) model was developed in mice to mimic the human situation, in which the vaccine virus does not replicate in the lower respiratory tract, allowing us to assess the protective efficacy of an H5N1 LAIV against highly pathogenic H5N1 virus challenge in the absence of significant pulmonary immunity. Our results show that, after one dose of an H5N1 LAIV, pulmonary influenza-specific lymphocytes are the main contributors to clearance of challenge virus from the lungs and that contributions of influenza-specific enzyme-linked immunosorbent assay (ELISA) antibodies in serum and splenic CD8+ T cells were negligible. Complete protection from H5N1 challenge was achieved after two doses of H5N1 LAIV and was associated with maturation of the antibody response. Although passive transfer of sera from mice that received two doses of vaccine prevented lethality in naive recipients following challenge, the mice showed significant weight loss, with high pulmonary titers of the H5N1 virus. These data highlight the importance of mucosal immunity in mediating optimal protection against H5N1 infection. Understanding the requirements for effective induction and establishment of these protective immune effectors in the respiratory tract paves the way for a more rational and effective vaccine approach in the future. PMID:22379093

  15. Influenza A non-H1N1 associated with acute respiratory failure and acute renal failure in a previously vaccinated cystic fibrosis patient

    PubMed Central

    Penteado, Louise Piva; Osório, Cecília Susin; Balbinotto, Antônio; Dalcin, Paulo de Tarso Roth

    2018-01-01

    In the 2014 - 2015 season, most influenza infections were due to A (H3N2) viruses. More than two-thirds of circulating A (H3N2) viruses are antigenically and genetically different (drifted) from the A (H3N2) vaccine component of 2014 - 2015 northern and southern Hemisphere seasonal influenza vaccines. The purpose of this paper is to report a case of seasonal influenza A non-H1N1 infection that occurred in June 2015 in an adult cystic fibrosis patient with severe lung disease previously vaccinated with the anti-flu trivalent vaccine. The patient evolved to respiratory and renal failure (without rhabdomyolysis) and was placed under mechanical ventilation and hemodialysis. The clinical outcome was positive after 39 days of hospital stay. In addition, the patient was clinically stable after 18 months of follow-up. With the recent advances in critical care medicine and in cystic fibrosis treatment, survival with advanced pulmonary disease in cystic fibrosis presents new questions and potential problems, which are still being formulated. PMID:29742226

  16. H1N1 antibody persistence 1 year after immunization with an adjuvanted or whole-virion pandemic vaccine and immunogenicity and reactogenicity of subsequent seasonal influenza vaccine: a multicenter follow-on study.

    PubMed

    Walker, Woolf T; de Whalley, Philip; Andrews, Nick; Oeser, Clarissa; Casey, Michelle; Michaelis, Louise; Hoschler, Katja; Harrill, Caroline; Moulsdale, Phoebe; Thompson, Ben; Jones, Claire; Chalk, Jem; Kerridge, Simon; John, Tessa M; Okike, Ifeanyichukwu; Ladhani, Shamez; Tomlinson, Richard; Heath, Paul T; Miller, Elizabeth; Faust, Saul N; Snape, Matthew D; Finn, Adam; Pollard, Andrew J

    2012-03-01

    We investigated antibody persistence in children 1 year after 2 doses of either an AS03(B)-adjuvanted split-virion or nonadjuvanted whole-virion monovalent pandemic influenza vaccine and assessed the immunogenicity and reactogenicity of a subsequent dose of trivalent influenza vaccine (TIV). Children previously immunized at age 6 months to 12 years in the original study were invited to participate. After a blood sample was obtained to assess persistence of antibody against swine influenza A/H1N1(2009) pandemic influenza, children received 1 dose of 2010/2011 TIV, reactogenicity data were collected for 7 days, and another blood sample was obtained 21 days after vaccination. Of 323 children recruited, 302 received TIV. Antibody persistence (defined as microneutralization [MN] titer ≥1:40) 1 year after initial vaccination was significantly higher in the AS03(B)-adjuvanted compared with the whole-virion vaccine group, 100% (95% confidence interval [CI], 94.1%-100%) vs 32.4% (95% CI, 21.5%-44.8%) in children immunized <3 years old and 96.9% (95% CI, 91.3%-99.4%) vs 65.9% (95% CI, 55.3%-75.5%) in those 3-12 years old at immunization, respectively (P < .001 for both groups). All children receiving TIV had post-vaccination MN titers ≥1:40. Although TIV was well tolerated in all groups, reactogenicity in children <5 years old was slightly greater in those who originally received AS03(B)-adjuvanted vaccine. This study provides serological evidence that 2 doses of AS03(B)-adjuvanted pandemic influenza vaccine may be sufficient to maintain protection across 2 influenza seasons. Administration of TIV to children who previously received 2 doses of either pandemic influenza vaccine is safe and is immunogenic for the H1N1 strain.

  17. H1N1 Antibody Persistence 1 Year After Immunization With an Adjuvanted or Whole-Virion Pandemic Vaccine and Immunogenicity and Reactogenicity of Subsequent Seasonal Influenza Vaccine: A Multicenter Follow-on Study

    PubMed Central

    Walker, Woolf T.; de Whalley, Philip; Andrews, Nick; Oeser, Clarissa; Casey, Michelle; Michaelis, Louise; Hoschler, Katja; Harrill, Caroline; Moulsdale, Phoebe; Thompson, Ben; Jones, Claire; Chalk, Jem; Kerridge, Simon; John, Tessa M.; Okike, Ifeanyichukwu; Ladhani, Shamez; Tomlinson, Richard; Heath, Paul T.; Miller, Elizabeth; Snape, Matthew D.; Finn, Adam; Pollard, Andrew J.

    2012-01-01

    Background. We investigated antibody persistence in children 1 year after 2 doses of either an AS03B-adjuvanted split-virion or nonadjuvanted whole-virion monovalent pandemic influenza vaccine and assessed the immunogenicity and reactogenicity of a subsequent dose of trivalent influenza vaccine (TIV). Methods. Children previously immunized at age 6 months to 12 years in the original study were invited to participate. After a blood sample was obtained to assess persistence of antibody against swine influenza A/H1N1(2009) pandemic influenza, children received 1 dose of 2010/2011 TIV, reactogenicity data were collected for 7 days, and another blood sample was obtained 21 days after vaccination. Results. Of 323 children recruited, 302 received TIV. Antibody persistence (defined as microneutralization [MN] titer ≥1:40) 1 year after initial vaccination was significantly higher in the AS03B-adjuvanted compared with the whole-virion vaccine group, 100% (95% confidence interval [CI], 94.1%–100%) vs 32.4% (95% CI, 21.5%–44.8%) in children immunized <3 years old and 96.9% (95% CI, 91.3%–99.4%) vs 65.9% (95% CI, 55.3%–75.5%) in those 3–12 years old at immunization, respectively (P < .001 for both groups). All children receiving TIV had post-vaccination MN titers ≥1:40. Although TIV was well tolerated in all groups, reactogenicity in children <5 years old was slightly greater in those who originally received AS03B-adjuvanted vaccine. Conclusions. This study provides serological evidence that 2 doses of AS03B-adjuvanted pandemic influenza vaccine may be sufficient to maintain protection across 2 influenza seasons. Administration of TIV to children who previously received 2 doses of either pandemic influenza vaccine is safe and is immunogenic for the H1N1 strain. PMID:22267719

  18. Diversity of the murine antibody response targeting influenza A(H1N1pdm09) hemagglutinin

    PubMed Central

    Wilson, Jason R.; Tzeng, Wen-Pin; Spesock, April; Music, Nedzad; Guo, Zhu; Barrington, Robert; Stevens, James; Donis, Ruben O.; Katz, Jacqueline M.; York, Ian A.

    2016-01-01

    We infected mice with the 2009 influenza A pandemic virus (H1N1pdm09), boosted with an inactivated vaccine, and cloned immunoglobulins (Igs) from HA-specific B cells. Based on the redundancy in germline gene utilization, we inferred that between 72–130 unique IgH VDJ and 35 different IgL VJ combinations comprised the anti-HA recall response. The IgH VH1 and IgL VK14 variable gene families were employed most frequently. A representative panel of antibodies were cloned and expressed to confirm reactivity with H1N1pdm09 HA. The majority of the recombinant antibodies were of high avidity and capable of inhibiting H1N1pdm09 hemagglutination. Three of these antibodies were subtype-specific cross-reactive, binding to the HA of A/South Carolina/1/1918(H1N1), and one further reacted with A/swine/Iowa/15/1930(H1N1). These results help define the genetic diversity of the influenza anti-HA antibody repertoire profile induced following infection and vaccination, which may facilitate the development of influenza vaccines that are more protective and broadly neutralizing. Importance Protection against influenza viruses is mediated mainly by antibodies, and in most cases this antibody response is narrow, only providing protection against closely-related viruses. In spite of this limited range of protection, recent findings indicate individuals immune to one influenza virus may contain antibodies (generally a minority of the overall response) that are more broadly reactive. These findings have raised the possibility that influenza vaccines could induce a more broadly protective response, reducing the need for frequent vaccine strain changes. However, interpretation of these observations is hampered by the lack of quantitative characterization of the antibody repertoire. In this study, we used single-cell cloning of influenza HA-specific B cells to assess the diversity and nature of the antibody response to influenza hemagglutinin in mice. Our findings help put bounds on the

  19. Diversity of the murine antibody response targeting influenza A(H1N1pdm09) hemagglutinin.

    PubMed

    Wilson, Jason R; Tzeng, Wen-Pin; Spesock, April; Music, Nedzad; Guo, Zhu; Barrington, Robert; Stevens, James; Donis, Ruben O; Katz, Jacqueline M; York, Ian A

    2014-06-01

    We infected mice with the 2009 influenza A pandemic virus (H1N1pdm09), boosted with an inactivated vaccine, and cloned immunoglobulins (Igs) from HA-specific B cells. Based on the redundancy in germline gene utilization, we inferred that between 72-130 unique IgH VDJ and 35 different IgL VJ combinations comprised the anti-HA recall response. The IgH VH1 and IgL VK14 variable gene families were employed most frequently. A representative panel of antibodies were cloned and expressed to confirm reactivity with H1N1pdm09 HA. The majority of the recombinant antibodies were of high avidity and capable of inhibiting H1N1pdm09 hemagglutination. Three of these antibodies were subtype-specific cross-reactive, binding to the HA of A/South Carolina/1/1918(H1N1), and one further reacted with A/swine/Iowa/15/1930(H1N1). These results help to define the genetic diversity of the influenza anti-HA antibody repertoire profile induced following infection and vaccination, which may facilitate the development of influenza vaccines that are more protective and broadly neutralizing. Protection against influenza viruses is mediated mainly by antibodies, and in most cases this antibody response is narrow, only providing protection against closely related viruses. In spite of this limited range of protection, recent findings indicate that individuals immune to one influenza virus may contain antibodies (generally a minority of the overall response) that are more broadly reactive. These findings have raised the possibility that influenza vaccines could induce a more broadly protective response, reducing the need for frequent vaccine strain changes. However, interpretation of these observations is hampered by the lack of quantitative characterization of the antibody repertoire. In this study, we used single-cell cloning of influenza HA-specific B cells to assess the diversity and nature of the antibody response to influenza hemagglutinin in mice. Our findings help to put bounds on the

  20. Correlates of 2009 Pandemic H1N1 Influenza Vaccine Acceptance among Middle and High School Teachers in Rural Georgia

    ERIC Educational Resources Information Center

    Gargano, Lisa M.; Painter, Julia E.; Sales, Jessica M.; Morfaw, Christopher; Jones, LaDawna M.; Weiss, Paul; Murray, Dennis; DiClemente, Ralph J.; Hughes, James M.

    2011-01-01

    Background: Teachers play an essential role in the school community, and H1N1 vaccination of teachers is critical to protect not only themselves but also adolescents they come in contact within the classroom through herd immunity. School-aged children have a greater risk of developing H1N1 disease than seasonal influenza. The goal of this study…

  1. Induction of protective immunity against H1N1 influenza A(H1N1)pdm09 with spray-dried and electron-beam sterilised vaccines in non-human primates.

    PubMed

    Scherließ, Regina; Ajmera, Ankur; Dennis, Mike; Carroll, Miles W; Altrichter, Jens; Silman, Nigel J; Scholz, Martin; Kemter, Kristina; Marriott, Anthony C

    2014-04-17

    Currently, the need for cooled storage and the impossibility of terminal sterilisation are major drawbacks in vaccine manufacturing and distribution. To overcome current restrictions a preclinical safety and efficacy study was conducted to evaluate new influenza A vaccine formulations regarding thermal resistance, resistance against irradiation-mediated damage and storage stability. We evaluated the efficacy of novel antigen stabilizing and protecting solutions (SPS) to protect influenza A(H1N1)pdm09 split virus antigen under experimental conditions in vitro and in vivo. Original or SPS re-buffered vaccine (Pandemrix) was spray-dried and terminally sterilised by irradiation with 25 kGy (e-beam). Antigen integrity was monitored by SDS-PAGE, dynamic light scattering, size exclusion chromatography and functional haemagglutination assays. In vitro screening experiments revealed a number of highly stable compositions containing glycyrrhizinic acid (GA) and/or chitosan. The most stable composition was selected for storage tests and in vivo assessment of seroconversion in non-human primates (Macaca fascicularis) using a prime-boost strategy. Redispersed formulations with original adjuvant were administered intramuscularly. Storage data revealed high stability of protected vaccines at 4°C and 25°C, 60% relative humidity, for at least three months. Animals receiving original Pandemrix exhibited expected levels of seroconversion after 21 days (prime) and 48 days (boost) as assessed by haemagglutination inhibition and microneutralisation assays. Animals vaccinated with spray-dried and irradiated Pandemrix failed to exhibit seroconversion after 21 days whereas spray-dried and irradiated, SPS-protected vaccines elicited similar seroconversion levels to those vaccinated with original Pandemrix. Boost immunisation with SPS-protected vaccine resulted in a strong increase in seroconversion but had only minor effects in animals treated with non SPS-protected vaccine. In conclusion

  2. Genetic Characterization of Influenza A (H1N1) Pandemic 2009 Virus Isolates from Mumbai.

    PubMed

    Gohil, Devanshi; Kothari, Sweta; Shinde, Pramod; Meharunkar, Rhuta; Warke, Rajas; Chowdhary, Abhay; Deshmukh, Ranjana

    2017-08-01

    Pandemic influenza A (H1N1) 2009 virus was first detected in India in May 2009 which subsequently became endemic in many parts of the country. Influenza A viruses have the ability to evade the immune response through its ability of antigenic variations. The study aims to characterize influenza A (H1N1) pdm 09 viruses circulating in Mumbai during the pandemic and post-pandemic period. Nasopharyngeal swabs positive for influenza A (H1N1) pdm 09 viruses were inoculated on Madin-Darby canine kidney cell line for virus isolation. Molecular and phylogenetic analysis of influenza A (H1N1) pdm 09 isolates was conducted to understand the evolution and genetic diversity of the strains. Nucleotide and amino acid sequences of the HA gene of Mumbai isolates when compared to A/California/07/2009-vaccine strain revealed 14 specific amino acid differences located at the antigenic sites. Amino acid variations in HA and NA gene resulted in changes in the N-linked glycosylation motif which may lead to immune evasion. Phylogenetic analysis of the isolates revealed their evolutionary position with vaccine strain A/California/07/2009 but had undergone changes gradually. The findings in the present study confirm genetic variability of influenza viruses and highlight the importance of continuous surveillance during influenza outbreaks.

  3. B Cell Response and Hemagglutinin Stalk-Reactive Antibody Production in Different Age Cohorts following 2009 H1N1 Influenza Virus Vaccination

    PubMed Central

    Baer, Jane; Santiago, Felix W.; Fitzgerald, Theresa; Ilyushina, Natalia A.; Sundararajan, Aarthi; Henn, Alicia D.; Krammer, Florian; Yang, Hongmei; Luke, Catherine J.; Zand, Martin S.; Wright, Peter F.; Treanor, John J.; Topham, David J.

    2013-01-01

    The 2009 pandemic H1N1 (pH1N1) influenza virus carried a swine-origin hemagglutinin (HA) that was closely related to the HAs of pre-1947 H1N1 viruses but highly divergent from the HAs of recently circulating H1N1 strains. Consequently, prior exposure to pH1N1-like viruses was mostly limited to individuals over the age of about 60 years. We related age and associated differences in immune history to the B cell response to an inactivated monovalent pH1N1 vaccine given intramuscularly to subjects in three age cohorts: 18 to 32 years, 60 to 69 years, and ≥70 years. The day 0 pH1N1-specific hemagglutination inhibition (HAI) and microneutralization (MN) titers were generally higher in the older cohorts, consistent with greater prevaccination exposure to pH1N1-like viruses. Most subjects in each cohort responded well to vaccination, with early formation of circulating virus-specific antibody (Ab)-secreting cells and ≥4-fold increases in HAI and MN titers. However, the response was strongest in the 18- to 32-year cohort. Circulating levels of HA stalk-reactive Abs were increased after vaccination, especially in the 18- to 32-year cohort, raising the possibility of elevated levels of cross-reactive neutralizing Abs. In the young cohort, an increase in MN activity against the seasonal influenza virus A/Brisbane/59/07 after vaccination was generally associated with an increase in the anti-Brisbane/59/07 HAI titer, suggesting an effect mediated primarily by HA head-reactive rather than stalk-reactive Abs. Our findings support recent proposals that immunization with a relatively novel HA favors the induction of Abs against conserved epitopes. They also emphasize the need to clarify how the level of circulating stalk-reactive Abs relates to resistance to influenza. PMID:23576673

  4. Measures against transmission of pandemic H1N1 influenza in Japan in 2009: simulation model.

    PubMed

    Yasuda, H; Suzuki, K

    2009-11-05

    The first outbreak of pandemic H1N1 influenza in Japan was contained in the Kansai region in May 2009 by social distancing measures. Modelling methods are needed to estimate the validity of these measures before their implementation on a large scale. We estimated the transmission coefficient from outbreaks of pandemic H1N1 influenza among school children in Japan in summer 2009; using this transmission coefficient, we simulated the spread of pandemic H1N1 influenza in a virtual community called the virtual Chuo Line which models an area to the west of metropolitan Tokyo. Measures evaluated in our simulation included: isolation at home, school closure, post-exposure prophylaxis and mass vaccinations of school children. We showed that post-exposure prophylaxis combined with isolation at home and school closure significantly decreases the total number of cases in the community and can mitigate the spread of pandemic H1N1 influenza, even when there is a delay in the availability of vaccine.

  5. Entrapment of H1N1 Influenza Virus Derived Conserved Peptides in PLGA Nanoparticles Enhances T Cell Response and Vaccine Efficacy in Pigs.

    PubMed

    Hiremath, Jagadish; Kang, Kyung-il; Xia, Ming; Elaish, Mohamed; Binjawadagi, Basavaraj; Ouyang, Kang; Dhakal, Santosh; Arcos, Jesus; Torrelles, Jordi B; Jiang, X; Lee, Chang Won; Renukaradhya, Gourapura J

    2016-01-01

    Pigs are believed to be one of the important sources of emerging human and swine influenza viruses (SwIV). Influenza virus conserved peptides have the potential to elicit cross-protective immune response, but without the help of potent adjuvant and delivery system they are poorly immunogenic. Biodegradable polylactic-co-glycolic acid (PLGA) nanoparticle (PLGA-NP) based vaccine delivery system enhances cross-presentation of antigens by the professional antigen presenting cells. In this study, Norovirus P particle containing SwIV M2e (extracellular domain of the matrix protein 2) chimera and highly conserved two each of H1N1 peptides of pandemic 2009 and classical human influenza viruses were entrapped in PLGA-NPs. Influenza antibody-free pigs were vaccinated with PLGA-NPs peptides cocktail vaccine twice with or without an adjuvant, Mycobacterium vaccae whole cell lysate, intranasally as mist. Vaccinated pigs were challenged with a virulent heterologous zoonotic SwIV H1N1, and one week later euthanized and the lung samples were analyzed for the specific immune response and viral load. Clinically, pigs vaccinated with PLGA-NP peptides vaccine had no fever and flu symptoms, and the replicating challenged SwIV was undetectable in the bronchoalveolar lavage fluid. Immunologically, PLGA-NP peptides vaccination (without adjuvant) significantly increased the frequency of antigen-specific IFNγ secreting CD4 and CD8 T cells response in the lung lymphocytes, despite not boosting the antibody response both at pre- and post-challenge. In summary, our data indicated that nanoparticle-mediated delivery of conserved H1N1 influenza peptides induced the virus specific T cell response in the lungs and reduced the challenged heterologous virus load in the airways of pigs.

  6. Safety and immunogenicity of an MF59-adjuvanted A/H1N1 pandemic influenza vaccine in children from three to seventeen years of age.

    PubMed

    Knuf, Markus; Leroux-Roels, Geert; Rümke, Hans C; Abarca, Katia; Rivera, Luis; Lattanzi, Maria; Pedotti, Paola; Arora, Ashwani; Kieninger-Baum, Dorothee; Della Cioppa, Giovanni

    2015-01-01

    This study was designed to identify the optimal dose of an MF59-adjuvanted, monovalent, A/H1N1 influenza vaccine in healthy paediatric subjects. Subjects aged 3-8 years (n=194) and 9-17 years (n=160) were randomized to receive two primary doses of A/H1N1 vaccine containing either 3.75 μg antigen with half a standard dose of MF59 adjuvant, 7.5 μg antigen with a full dose of MF59, or (children 3-8 years only), a non-adjuvanted 15 μg formulation. A booster dose of MF59-adjuvanted seasonal influenza vaccine including homologous A/H1N1 strain was given one year after priming. Immunogenicity was assessed by haemagglutination inhibition (HI) and microneutralization assays. Vaccine safety was assessed throughout the study (up to 18 months). A single priming dose of either MF59-adjuvanted formulation was sufficient to meet the European licensure criteria for pandemic influenza vaccines (HI titres ≥1:40>70%; seroconversion>40%; and GMR>2.5). Two non-adjuvanted vaccine doses were required to meet the same licensure criteria. After first and second doses, percentage of subjects with HI titres ≥1:40 were between 97% and 100% in the adjuvanted vaccine groups compared with 68% and 91% in the non-adjuvanted group, respectively. Postvaccination seroconversion rates ranged from 91% to 98% in adjuvanted groups and were 68% (first dose) and 98% (second dose) in the non-adjuvanted group. HI titres ≥1:330 after primary doses were achieved in 69% to 90% in adjuvanted groups compared with 41% in the non-adjuvanted group. Long-term antibody persistence after priming and a robust antibody response to booster immunization were observed in all vaccination groups. All A/H1N1 vaccine formulations were generally well tolerated. No vaccine-related serious adverse events occurred, and no subjects were withdrawn from the study due to an adverse event. An MF59-adjuvanted influenza vaccine containing 3.75 μg of A/H1N1 antigen was well tolerated and sufficiently immunogenic to meet all the

  7. Pandemic (H1N1) 2009 and Hajj Pilgrims Who Received Predeparture Vaccination, Egypt

    PubMed Central

    Kandeel, Amr; Abdel Kereem, Eman; El-Refay, Samir; Afifi, Salma; Abukela, Mohammed; Earhart, Kenneth; El-Sayed, Nasr; El-Gabaly, Hatem

    2011-01-01

    In Egypt, vaccination against pandemic (H1N1) 2009 virus was required of pilgrims departing for the 2009 Hajj. A survey of 551 pilgrims as they returned to Egypt found 542 (98.1% [weighted]) reported receiving the vaccine; 6 (1.0% [weighted]) were infected with influenza virus A (H3N2) but none with pandemic (H1N1) 2009 virus. PMID:21762583

  8. Cross-protective efficacies of highly-pathogenic avian influenza H5N1 vaccines against a recent H5N8 virus.

    PubMed

    Park, Su-Jin; Si, Young-Jae; Kim, Jihye; Song, Min-Suk; Kim, Se-Mi; Kim, Eun-Ha; Kwon, Hyeok-Il; Kim, Young-Il; Lee, Ok-Jun; Shin, Ok Sarah; Kim, Chul-Joong; Shin, Eui-Cheol; Choi, Young Ki

    2016-11-01

    To investigate cross-protective vaccine efficacy of highly-pathogenic avian influenza H5N1 viruses against a recent HPAI H5N8 virus, we immunized C57BL/6 mice and ferrets with three alum-adjuvanted inactivated whole H5N1 vaccines developed through reverse-genetics (Rg): [Vietnam/1194/04xPR8 (clade 1), Korea/W149/06xPR8 (clade 2.2), and Korea/ES223N/03xPR8 (clade 2.5)]. Although relatively low cross-reactivities (10-40 HI titer) were observed against heterologous H5N8 virus, immunized animals were 100% protected from challenge with the 20 mLD50 of H5N8 virus, with the exception of mice vaccinated with 3.5μg of Rg Vietnam/1194/04xPR8. Of note, the Rg Korea/ES223N/03xPR8 vaccine provided not only effective protection, but also markedly inhibited viral replication in the lungs and nasal swabs of vaccine recipients within five days of HPAI H5N8 virus challenge. Further, we demonstrated that antibody-dependent cell-mediated cytotoxicity (ADCC) of an antibody-coated target cell by cytotoxic effector cells also plays a role in the heterologous protection of H5N1 vaccines against H5N8 challenge. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. The transmissibility and control of pandemic influenza A (H1N1) virus.

    PubMed

    Yang, Yang; Sugimoto, Jonathan D; Halloran, M Elizabeth; Basta, Nicole E; Chao, Dennis L; Matrajt, Laura; Potter, Gail; Kenah, Eben; Longini, Ira M

    2009-10-30

    Pandemic influenza A (H1N1) 2009 (pandemic H1N1) is spreading throughout the planet. It has become the dominant strain in the Southern Hemisphere, where the influenza season has now ended. Here, on the basis of reported case clusters in the United States, we estimated the household secondary attack rate for pandemic H1N1 to be 27.3% [95% confidence interval (CI) from 12.2% to 50.5%]. From a school outbreak, we estimated that a typical schoolchild infects 2.4 (95% CI from 1.8 to 3.2) other children within the school. We estimated the basic reproductive number, R0, to range from 1.3 to 1.7 and the generation interval to range from 2.6 to 3.2 days. We used a simulation model to evaluate the effectiveness of vaccination strategies in the United States for fall 2009. If a vaccine were available soon enough, vaccination of children, followed by adults, reaching 70% overall coverage, in addition to high-risk and essential workforce groups, could mitigate a severe epidemic.

  10. Heterologous Prime-Boost Vaccination Using an AS03B-Adjuvanted Influenza A(H5N1) Vaccine in Infants and Children <3 Years of Age

    PubMed Central

    Nolan, Terry; Izurieta, Patricia; Lee, Bee-Wah; Chan, Poh Chong; Marshall, Helen; Booy, Robert; Drame, Mamadou; Vaughn, David W.

    2014-01-01

    Background. Protecting young children from pandemic influenza should also reduce transmission to susceptible adults, including pregnant women. Methods. An open study assessed immunogenicity and reactogenicity of a heterologous booster dose of A/turkey/Turkey/1/2005(H5N1)-AS03B (AS03B is an Adjuvant System containing α-tocopherol and squalene in an oil-in-water emulsion [5.93 mg tocopherol]) in infants and children aged 6 to < 36 months that was given 6 months following 2-dose primary vaccination with A/Indonesia/05/2005(H5N1)-AS03B. Vaccines contained 1.9 µg of hemagglutinin antigen and AS03B. Hemagglutinin inhibition (HI) responses, microneutralization titers, and antineuraminidase antibody levels were assessed for 6 months following the booster vaccination. Results. For each age stratum (defined on the basis of the subject's age at first vaccination as 6 to < 12 months, 12 to < 24 months, and 24 to < 36 months) and overall (n = 113), European influenza vaccine licensure criteria were fulfilled for responses to A/turkey/Turkey/1/2005(H5N1) 10 days following the booster vaccination. Local pain and fever increased with consecutive doses. Anamnestic immune responses were demonstrated for HI, neutralizing, and antineuraminidase antibodies against vaccine-homologous/heterologous strains. Antibody responses to vaccine-homologous/heterologous strains persisted in all children 6 months following the booster vaccination. Conclusions. Prevaccination of young children with a clade 2 strain influenza A(H5N1) AS03-adjuvanted vaccine followed by heterologous booster vaccination boosted immune responses to the homologous strain and a related clade, with persistence for at least 6 months. The results support a prime-boost vaccination approach in young children for pandemic influenza preparedness. Clinical Trials Registration. NCT01323946. PMID:24973461

  11. Distribution of avian influenza H5N1 viral RNA in tissues of AI-vaccinated and unvaccinated contact chickens after experimental infection.

    PubMed

    Hassan, Mohamed K; Kilany, Walid H; Abdelwhab, E M; Arafa, Abdel-Satar; Selim, Abdullah; Samy, Ahmed; Samir, M; Le Brun, Yvon; Jobre, Yilma; Aly, Mona M

    2012-05-01

    Avian influenza due to highly pathogenic avian influenza (HPAIV) H5N1 virus is not a food-borne illness but a serious panzootic disease with the potential to be pandemic. In this study, broiler chickens were vaccinated with commercial H5N1 or H5N2 inactivated vaccines prior to being challenged with an HPAIV H5N1 (clade 2.2.1 classic) virus. Challenged and non-challenged vaccinated chickens were kept together, and unvaccinated chickens served as contact groups. Post-challenge samples from skin and edible internal organs were collected from dead and sacrificed (after a 14-day observation period) birds and tested using qRT-PCR for virus detection and quantification. H5N1 vaccine protected chickens against morbidity, mortality and transmission. Virus RNA was not detected in the meat or edible organs of chickens vaccinated with H5N1 vaccine. Conversely, H5N2 vaccine did not confer clinical protection, and a significant virus load was detected in the meat and internal organs. Phylogenetic analysis showed that the H5N1 virus vaccine and challenge virus strains are closely related. The results of the present study strongly suggest a need for proper selection of vaccines and their routine evaluation against newly emergent field viruses. These actions will help to reduce human exposure to HPAIV H5N1 virus from both infected live birds and slaughtered poultry. In addition, rigorous preventive measures should be put in place in order to minimize the public-health risks of avian influenza at the human-animal interface.

  12. Development and characterization of a panel of cross-reactive monoclonal antibodies generated using H1N1 influenza virus.

    PubMed

    Guo, Chun-yan; Tang, Yi-gui; Qi, Zong-li; Liu, Yang; Zhao, Xiang-rong; Huo, Xue-ping; Li, Yan; Feng, Qing; Zhao, Peng-hua; Wang, Xin; Li, Yuan; Wang, Hai-fang; Hu, Jun; Zhang, Xin-jian

    2015-08-01

    To characterize the antigenic epitopes of the hemagglutinin (HA) protein of H1N1 influenza virus, a panel consisting of 84 clones of murine monoclonal antibodies (mAbs) were generated using the HA proteins from the 2009 pandemic H1N1 vaccine lysate and the seasonal influenza H1N1(A1) vaccines. Thirty-three (39%) of the 84 mAbs were found to be strain-specific, and 6 (7%) of the 84 mAbs were subtype-specific. Twenty (24%) of the 84 mAbs recognized the common HA epitopes shared by 2009 pandemic H1N1, seasonal A1 (H1N1), and A3 (H3N2) influenza viruses. Twenty-five of the 84 clones recognized the common HA epitopes shared by the 2009 pandemic H1N1, seasonal A1 (H1N1) and A3 (H3N2) human influenza viruses, and H5N1 and H9N2 avian influenza viruses. We found that of the 16 (19%) clones of the 84 mAbs panel that were cross-reactive with human respiratory pathogens, 15 were made using the HA of the seasonal A1 (H1N1) virus and 1 was made using the HA of the 2009 pandemic H1N1 influenza virus. Immunohistochemical analysis of the tissue microarray (TMA) showed that 4 of the 84 mAb clones cross-reacted with human tissue (brain and pancreas). Our results indicated that the influenza virus HA antigenic epitopes not only induce type-, subtype-, and strain-specific monoclonal antibodies against influenza A virus but also cross-reactive monoclonal antibodies against human tissues. Further investigations of these cross-reactive (heterophilic) epitopes may significantly improve our understanding of viral antigenic variation, epidemics, pathophysiologic mechanisms, and adverse effects of influenza vaccines. Copyright © 2015 Elsevier GmbH. All rights reserved.

  13. Guillain-Barré syndrome and adjuvanted pandemic influenza A (H1N1) 2009 vaccine: multinational case-control study in Europe

    PubMed Central

    Dieleman, Jeanne; Romio, Silvana; Johansen, Kari; Weibel, Daniel; Bonhoeffer, Jan

    2011-01-01

    Objective To assess the association between pandemic influenza A (H1N1) 2009 vaccine and Guillain-Barré syndrome. Design Case-control study. Setting Five European countries. Participants 104 patients with Guillain-Barré syndrome and its variant Miller-Fisher syndrome matched to one or more controls. Case status was classified according to the Brighton Collaboration definition. Controls were matched to cases on age, sex, index date, and country. Main outcome measures Relative risk estimate for Guillain-Barré syndrome after pandemic influenza vaccine. Results Case recruitment and vaccine coverage varied considerably between countries; the most common vaccines used were adjuvanted (Pandemrix and Focetria). The unadjusted pooled risk estimate for all countries was 2.8 (95% confidence interval 1.3 to 6.0). After adjustment for influenza-like illness/upper respiratory tract infection and seasonal influenza vaccination, receipt of pandemic influenza vaccine was not associated with an increased risk of Guillain-Barré syndrome (adjusted odds ratio 1.0, 0.3 to 2.7). The 95% confidence interval shows that the absolute effect of vaccination could range from one avoided case of Guillain-Barré syndrome up to three excess cases within six weeks after vaccination in one million people. Conclusions The risk of occurrence of Guillain-Barré syndrome is not increased after pandemic influenza vaccine, although the upper limit does not exclude a potential increase in risk up to 2.7-fold or three excess cases per one million vaccinated people. When assessing the association between pandemic influenza vaccines and Guillain-Barré syndrome it is important to account for the effects of influenza-like illness/upper respiratory tract infection, seasonal influenza vaccination, and calendar time. PMID:21750072

  14. Mammalian-transmissible H5N1 influenza: facts and perspective.

    PubMed

    Osterholm, Michael T; Kelley, Nicholas S

    2012-01-01

    Two recently submitted (but as yet unpublished) studies describe success in creating mutant isolates of H5N1 influenza A virus that can be transmitted via the respiratory route between ferrets; concern has been raised regarding human-to-human transmissibility of these or similar laboratory-generated influenza viruses. Furthermore, the potential release of methods used in these studies has engendered a great deal of controversy around publishing potential dual-use data and also has served as a catalyst for debates around the true case-fatality rate of H5N1 influenza and the capability of influenza vaccines and antivirals to impact any future unintentional or intentional release of H5N1 virus. In this report, we review available seroepidemiology data for H5N1 infection and discuss how case-finding strategies may influence the overall case-fatality rate reported by the WHO. We also provide information supporting the position that if an H5N1 influenza pandemic occurred, available medical countermeasures would have limited impact on the associated morbidity and mortality. Copyright © 2012 Osterholm et al.

  15. [Dynamics of cytokine production in adults after administration of influenza vaccine from A/California/7/2009 (H1N1) strain].

    PubMed

    Terkacheva, O A; Kostinov, M P; Zhirova, S N; Cherdantsev, A P

    2012-01-01

    Study dynamics of IFNalpha, IFNgamma, TNFalpha cytokines in healthy adults after administration of inactivated subunit monovalent influenza vaccine, A/California/7/2009 (H1N1) strain. Levels of IFNalpha, IFNgamma, TNFalpha cytokines were studied in blood sera of 58 mostly healthy adults aged 18 - 60 years. Kits for enzyme immunoassay determination of cytokine levels (Vector-Best, Novosibirsk) were used in the study. Antibody titers to A/California/7/2009 (H1N1) strain were determined at analogous time by using microneutralization reaction (MNR). Changes in the level of IFNalpha, IFNgamma, TNFalpha in healthy volunteers immunized by pandemic influenza vaccine were evaluated. Vaccine was safe. Two immunizations did not result in an increase of TNFalpha level that is an additional evidence of vaccine safety. IFNalpha level had a tendency to increase in vaccinated volunteers. IFNgamma levels in volunteers with normal level of this cytokine (below 10 pg/ml) were increased significantly after the second immunization (from 2.66 +/- 2.48 to 5.21 +/- 2.56). Correlation analysis showed that there is a strong negative association between IFNalpha, IFNgamma and seroconversion.

  16. Towards a sane and rational approach to management of Influenza H1N1 2009.

    PubMed

    Gallaher, William R

    2009-05-07

    Beginning in March 2009, an outbreak of influenza in North America was found to be caused by a new strain of influenza virus, designated Influenza H1N1 2009, which is a reassortant of swine, avian and human influenza viruses. Over a thousand total cases were identified with the first month, chiefly in the United States and Mexico, but also involving several European countries. Actions concerning Influenza H1N1 2009 need to be based on fact and science, following recommendations of public health officials, and not fueled by political, legal or other interests. Every influenza outbreak or pandemic is unique, so the facts of each one must be studied before an appropriate response can be developed. While reports are preliminary, through the first 4 weeks of the outbreak it does not appear to be severe either in terms of the attack rate in communities or in the virulence of the virus itself. However, there are significant changes in both the hemagglutinin and neuraminidase proteins of the new virus, 27.2% and 18.2% of the amino acid sequence, from prior H1N1 isolates in 2008 and the current vaccine. Such a degree of change qualifies as an "antigenic shift", even while the virus remains in the H1N1 family of influenza viruses, and may give influenza H1N1 2009 significant pandemic potential. Perhaps balancing this shift, the novel virus retains more of the core influenza proteins from animal strains than successful human influenza viruses, and may be inhibited from its maximum potential until further reassortment or mutation better adapts it to multiplication in humans. While contact and respiratory precautions such as frequent handwashing will slow the virus through the human population, it is likely that development of a new influenza vaccine tailored to this novel Influenza H1N1 2009 strain will be essential to blunt its ultimate pandemic impact.

  17. Towards a sane and rational approach to management of Influenza H1N1 2009

    PubMed Central

    Gallaher, William R

    2009-01-01

    Beginning in March 2009, an outbreak of influenza in North America was found to be caused by a new strain of influenza virus, designated Influenza H1N1 2009, which is a reassortant of swine, avian and human influenza viruses. Over a thousand total cases were identified with the first month, chiefly in the United States and Mexico, but also involving several European countries. Actions concerning Influenza H1N1 2009 need to be based on fact and science, following recommendations of public health officials, and not fueled by political, legal or other interests. Every influenza outbreak or pandemic is unique, so the facts of each one must be studied before an appropriate response can be developed. While reports are preliminary, through the first 4 weeks of the outbreak it does not appear to be severe either in terms of the attack rate in communities or in the virulence of the virus itself. However, there are significant changes in both the hemagglutinin and neuraminidase proteins of the new virus, 27.2% and 18.2% of the amino acid sequence, from prior H1N1 isolates in 2008 and the current vaccine. Such a degree of change qualifies as an "antigenic shift", even while the virus remains in the H1N1 family of influenza viruses, and may give influenza H1N1 2009 significant pandemic potential. Perhaps balancing this shift, the novel virus retains more of the core influenza proteins from animal strains than successful human influenza viruses, and may be inhibited from its maximum potential until further reassortment or mutation better adapts it to multiplication in humans. While contact and respiratory precautions such as frequent handwashing will slow the virus through the human population, it is likely that development of a new influenza vaccine tailored to this novel Influenza H1N1 2009 strain will be essential to blunt its ultimate pandemic impact. PMID:19422701

  18. Fever following immunization with influenza A (H1N1) vaccine in children: a survey-based study in the Netherlands.

    PubMed

    Broos, Nancy; van Puijenbroek, Eugène P; van Grootheest, Kees

    2010-12-01

    In November 2009, all children in the Netherlands from 6 months up to 4 years of age were indicated to receive the Influenza A (H1N1) vaccine. Fever is a common adverse event following immunization in children. Pandemrix®, an inactivated, split-virus influenza A (H1N1) vaccine, was used for this age group. A clinical study mentioned in the Summary of Product Characteristics of Pandemrix® found an increased reactogenicity after the second dose in comparison with the first dose, particularly in the rate of fever. In the Netherlands, this adverse reaction was a point of concern for the parents or caregivers of these children. To investigate the course and height of fever following the first and second dose of Pandemrix® in children aged from 6 months up to 4 years. The secondary aim was to evaluate the use of an online survey during a vaccination campaign. Survey-based descriptive study. Adverse drug reaction reporting database of the Netherlands Pharmacovigilance Centre (Lareb). Parents or caregivers (n = 839) of vaccinated children who reported fever to Lareb following the first immunization with Pandemrix®. Questionnaires were sent by email to parents or caregivers of eligible children following the first and second doses of Pandremix®. Time between vaccination and the occurrence of fever, the maximum measured temperature, the occurrence of other adverse events after first and second vaccination, the decision to get the second vaccination and the social implication of the fever in terms of absence from work, nursery or school, and hospitalization. Following the first vaccination against Influenza A (H1N1), the height of the fever was between 39.0 and 40.0°C in 359/639 (56.2%) of the children. In most of these children (235/639 [36.8%]), the onset of fever was between 6 and 12 hours following vaccination. 450/639 (70.4%) children recovered within 2 days. Of the 539 responders to the second questionnaire, 380 (70.5%) received the second vaccination against

  19. Local health department 2009 H1N1 influenza vaccination clinics-CDC staffing model comparison and other best practices.

    PubMed

    Porter, Dayna; Hall, Mark; Hartl, Brian; Raevsky, Cathy; Peacock, Roberta; Kraker, David; Walls, Sandra; Brink, Gail

    2011-01-01

    Mass vaccination clinic staffing models, such as the Centers for Disease Control and Prevention Large-Scale Vaccination Clinic Output and Staff Estimates: An Example, provide guidance on appropriate roles and number of staff for successful mass vaccination clinics within local and state health departments. The Kent County Health Department used this model as a starting point for mass vaccination clinics in response to 2009 H1N1 influenza. In addition to discussion of successful modification of the Centers for Disease Control and Prevention model to maximize local health department mass vaccination clinic efficiency, additional best practices including use of the Incident Command System and a reservation system are provided. Use of the provided modified staffing model and additional best practices will increase the success of health department mass vaccination clinics, and should be considered not only for future public health emergencies, but also for seasonal influenza vaccination campaigns.

  20. Safety of pandemic H1N1 vaccines in children and adolescents.

    PubMed

    Wijnans, Leonoor; de Bie, Sandra; Dieleman, Jeanne; Bonhoeffer, Jan; Sturkenboom, Miriam

    2011-10-06

    During the 2009 influenza A (H1N1) pandemic several pandemic H1N1 vaccines were licensed using fast track procedures, with relatively limited data on the safety in children and adolescents. Different extensive safety monitoring efforts were put in place to ensure timely detection of adverse events following immunization. These combined efforts have generated large amounts of data on the safety of the different pandemic H1N1 vaccines, also in children and adolescents. In this overview we shortly summarize the safety experience with seasonal influenza vaccines as a background and focus on the clinical and post marketing safety data of the pandemic H1N1 vaccines in children. We identified 25 different clinical studies including 10,505 children and adolescents, both healthy and with underlying medical conditions, between the ages of 6 months and 23 years. In addition, large monitoring efforts have resulted in large amounts of data, with almost 13,000 individual case reports in children and adolescents to the WHO. However, the diversity in methods and data presentation in clinical study publications and publications of spontaneous reports hampered the analysis of safety of the different vaccines. As a result, relatively little has been learned on the comparative safety of these pandemic H1N1 vaccines - particularly in children. It should be a collective effort to give added value to the enormous work going into the individual studies by adhering to available guidelines for the collection, analysis, and presentation of vaccine safety data in clinical studies and to guidance for the clinical investigation of medicinal products in the pediatric population. Importantly the pandemic has brought us the beginning of an infrastructure for collaborative vaccine safety studies in the EU, USA and globally. Copyright © 2011 Elsevier Ltd. All rights reserved.

  1. Association between the 2008-09 seasonal influenza vaccine and pandemic H1N1 illness during Spring-Summer 2009: four observational studies from Canada.

    PubMed

    Skowronski, Danuta M; De Serres, Gaston; Crowcroft, Natasha S; Janjua, Naveed Z; Boulianne, Nicole; Hottes, Travis S; Rosella, Laura C; Dickinson, James A; Gilca, Rodica; Sethi, Pam; Ouhoummane, Najwa; Willison, Donald J; Rouleau, Isabelle; Petric, Martin; Fonseca, Kevin; Drews, Steven J; Rebbapragada, Anuradha; Charest, Hugues; Hamelin, Marie-Eve; Boivin, Guy; Gardy, Jennifer L; Li, Yan; Kwindt, Trijntje L; Patrick, David M; Brunham, Robert C

    2010-04-06

    In late spring 2009, concern was raised in Canada that prior vaccination with the 2008-09 trivalent inactivated influenza vaccine (TIV) was associated with increased risk of pandemic influenza A (H1N1) (pH1N1) illness. Several epidemiologic investigations were conducted through the summer to assess this putative association. (1) test-negative case-control design based on Canada's sentinel vaccine effectiveness monitoring system in British Columbia, Alberta, Ontario, and Quebec; (2) conventional case-control design using population controls in Quebec; (3) test-negative case-control design in Ontario; and (4) prospective household transmission (cohort) study in Quebec. Logistic regression was used to estimate odds ratios for TIV effect on community- or hospital-based laboratory-confirmed seasonal or pH1N1 influenza cases compared to controls with restriction, stratification, and adjustment for covariates including combinations of age, sex, comorbidity, timeliness of medical visit, prior physician visits, and/or health care worker (HCW) status. For the prospective study risk ratios were computed. Based on the sentinel study of 672 cases and 857 controls, 2008-09 TIV was associated with statistically significant protection against seasonal influenza (odds ratio 0.44, 95% CI 0.33-0.59). In contrast, estimates from the sentinel and three other observational studies, involving a total of 1,226 laboratory-confirmed pH1N1 cases and 1,505 controls, indicated that prior receipt of 2008-09 TIV was associated with increased risk of medically attended pH1N1 illness during the spring-summer 2009, with estimated risk or odds ratios ranging from 1.4 to 2.5. Risk of pH1N1 hospitalization was not further increased among vaccinated people when comparing hospitalized to community cases. Prior receipt of 2008-09 TIV was associated with increased risk of medically attended pH1N1 illness during the spring-summer 2009 in Canada. The occurrence of bias (selection, information) or

  2. Antibody responses to natural influenza A/H1N1/09 disease or following immunization with adjuvanted vaccines, in immunocompetent and immunocompromised children.

    PubMed

    Meier, Sara; Bel, Michael; L'huillier, Arnaud; Crisinel, Pierre-Alex; Combescure, Christophe; Kaiser, Laurent; Grillet, Stéphane; Pósfay-Barbe, Klara; Siegrist, Claire-Anne

    2011-04-27

    To compare antibody responses elicited by influenza A/H1N1/09 disease and immunization with adjuvanted vaccines, in immunocompetent or immunocompromised children. Prospective parallel cohort field study enrolling children with confirmed influenza A/H1N1/09 disease or immunized with 1 (immunocompetent) or 2 (immunocompromised) doses of influenza A/H1N1/09 squalene-based AS03- or MF59-adjuvanted vaccines. Antibody geometric mean titers (GMT) were measured by hemagglutination inhibition (HAI) and microneutralization (MN) assays 4-6 weeks after vaccination/disease. Vaccine adverse events were self-recorded in a 7-day diary. Antibody titers were as high in 48 immunocompetent children after a single immunization (HAI and MN seroprotection rates: 98%; HAI-GMT: 395, MN-GMT: 370) as in 51 convalescent children (seroprotection rates: 98% (HAI) and 92% (MN); GMT: 350 (HAI) and 212 (MN). Twenty-seven immunocompromised children reached slightly lower seroprotection rates (HAI: 89%, MN: 85%) but similar antibody titers (HAI-GMT: 306, MN-GMT: 225) after 2 immunizations. Adverse events increased with age (P=0.01) and were more frequent with Pandemrix® than Focetria® (P=0.03). Similarly high seroresponses may be expected in immunocompetent children after a single dose of adjuvanted vaccines as responses of convalescent children. Two vaccine doses were sufficient for most immunocompromised children. NCT0102293 and NCT01022905. Copyright © 2011 Elsevier Ltd. All rights reserved.

  3. US school morbidity and mortality, mandatory vaccination, institution closure, and interventions implemented during the 2009 influenza A H1N1 pandemic.

    PubMed

    Rebmann, Terri; Elliott, Michael B; Swick, Zachary; Reddick, David

    2013-03-01

    The 2009 H1N1 pandemic disproportionately affected school-aged children, but only school-based outbreak case studies have been conducted. The purposes of this study were to evaluate US academic institutions' experiences during the 2009 H1N1 pandemic in terms of infection prevention interventions implemented and to examine factors associated with school closure during the pandemic. An online survey was sent to school nurses in May through July 2011. Hierarchical logistic regressions were used to determine predictive models for having a mandatory H1N1 vaccination policy for school nurses and school closure. In all, 1,997 nurses from 26 states participated. Very few nurses (3.3%, n=65) reported having a mandatory H1N1 influenza vaccination policy; nurses were more likely than all other school employees (p<.001) to be mandated to receive vaccine. Determinants of having a mandatory H1N1 vaccination policy were being employed by a hospital or public health agency, and the school being located in a western or northeastern state. Factors related to school closure included being in a western or northeastern state, having higher H1N1-related morbidity/mortality, being a school nurse employed by a public health agency or hospital, and being a private school. The most commonly implemented interventions included encouraging staff and students to exercise hand hygiene and increasing classroom cleaning; least commonly implemented interventions included discouraging face-to-face meetings, training staff on H1N1 influenza and/or respiratory hygiene, and discouraging handshaking. Schools should develop and continue to improve their pandemic plans, including collaborating with community response agencies.

  4. Association of vaccine handling conditions with effectiveness of live attenuated influenza vaccine against H1N1pdm09 viruses in the United States.

    PubMed

    Caspard, Herve; Coelingh, Kathleen L; Mallory, Raburn M; Ambrose, Christopher S

    2016-09-30

    This analysis examined potential causes of the lack of vaccine effectiveness (VE) of live attenuated influenza vaccine (LAIV) against A/H1N1pdm09 viruses in the United States (US) during the 2013-2014 season. Laboratory studies have demonstrated reduced thermal stability of A/California/07/2009, the A/H1N1pdm09 strain utilized in LAIV from 2009 through 2013-2014. Post hoc analyses of a 2013-2014 test-negative case-control (TNCC) effectiveness study investigated associations between vaccine shipping conditions and LAIV lot effectiveness. Investigational sites provided the LAIV lot numbers administered to each LAIV recipient enrolled in the study, and the vaccine distributor used by the site for commercially purchased vaccine. Additionally, a review was conducted of 2009-2014 pediatric observational TNCC effectiveness studies of LAIV, summarizing effectiveness by type/subtype, season, and geographic location. From the 2013 to 2014 TNCC study, the proportion of LAIV recipients who tested positive for H1N1pdm09 was significantly higher among children who received a lot released between August 1 and September 15, 2013, compared with a lot shipped either earlier or later (21% versus 4%; P<0.01). A linear relationship was observed between the proportion of subjects testing positive for H1N1pdm09 and outdoor temperatures during truck unloading at distributors' central locations. The review of LAIV VE studies showed that in the 2010-2011 and 2013-2014 influenza seasons, no significant effectiveness of LAIV against H1N1pdm09 was demonstrated for the trivalent or quadrivalent formulations of LAIV in the US, respectively, in contrast to significant effectiveness against A/H3N2 and B strains during 2010-2014. This study showed that the lack of VE observed with LAIV in the US against H1N1pdm09 viruses was associated with exposure of some LAIV lots to temperatures above recommended storage conditions during US distribution, and is likely explained by the increased susceptibility

  5. Leptin and leptin-related gene polymorphisms, obesity, and influenza A/H1N1 vaccine-induced immune responses in older individuals.

    PubMed

    Ovsyannikova, Inna G; White, Sarah J; Larrabee, Beth R; Grill, Diane E; Jacobson, Robert M; Poland, Gregory A

    2014-02-07

    Obesity is a risk factor for complicated influenza A/H1N1 disease and poor vaccine immunogenicity. Leptin, an adipocyte-derived hormone/cytokine, has many immune regulatory functions and therefore could explain susceptibility to infections and poor vaccine outcomes. We recruited 159 healthy adults (50-74 years old) who were immunized with inactivated TIV influenza vaccine that contained A/California/7/2009/H1N1 virus. We found a strong correlation between leptin concentration and BMI (r=0.55, p<0.0001), but no association with hemagglutination antibody inhibition (HAI), B-cell, or granzyme B responses. We found a slight correlation between leptin concentration and an immunosenescence marker (TREC: T-cell receptor excision circles) level (r=0.23, p=0.01). We found eight SNPs in the LEP/LEPR/GHRL genes that were associated with leptin levels and four SNPs in the PTPN1/LEPR/STAT3 genes associated with peripheral blood TREC levels (p<0.05). Heterozygosity of the synonymous variant rs2230604 in the PTPN1 gene was associated with a significantly lower (531 vs. 259, p=0.005) TREC level, as compared to the homozygous major variant. We also found eight SNPs in the LEP/PPARG/CRP genes associated with variations in influenza-specific HAI and B-cell responses (p<0.05). Our results suggest that specific allelic variations in the leptin-related genes may influence adaptive immune responses to influenza vaccine. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. [Adverse effects of seasonal flu vaccine and new influenza A (H1N1) vaccine in health care workers].

    PubMed

    Torruella, Joan Inglés; Soto, Rosa Gil; Valls, Rosa Carreras; Lozano, Judit Valverde; Carreras, Dolors Benito; Cunillera, Arnau Besora

    2013-01-01

    To assess and compare adverse effects of Seasonal Influenza Vaccine (SIV) and new Influenza A(H1N1) Vaccine (AIV) in health care workers. Multicenter cross-sectional study in health care workers from acute care hospitals, primary health care centers, social centers, mental health centers and a geriatric hospital participating in the 2009 vaccination campaign. Self-administered questionnaires were sent to all workers vaccinated with SIV and/or AIV. 527 valid questionnaires were collected out of 1123 sent to SIV vaccinated workers (46.9%), and 241 out of 461 sent to AIV vaccinated workers (52.%%). Participant workers include 527 vaccinated only with SIV, 117 first vaccinated with SIV and later with AIV (SIV+AIV), and 125 vaccinated only with AIV. Overall, 18.4% (95%CI 15.1-21.7) of workers vaccinated only with SIV reported adverse effects, as compared to 45.3% (95I 36.3-54.3) reporting adverse effects to AIV in the SIV+AIV group and 46.4% (95%CI 37.7-55.1) of workers vaccinated only with AIV. In all participants the most common adverseeffect was a local reaction. Women wre more reactive to both SIV and AIV than men. In all age groups SIV vaccination alone caused fewer reactions that either AIV only or the combination of SIV+AIV, with the exception of workers below 29 years of age. AIV was associated with more reactions than SIV, with no differences observed in relation to administration sequence. There were differences by sex and age, but reactions always occurred more commonly with AIV. Copyright belongs to the Societat Catalana de Seguretat i Medicina del Treball.

  7. High-yield production of a stable Vero cell-based vaccine candidate against the highly pathogenic avian influenza virus H5N1

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Zhou, Fangye; Zhou, Jian; Ma, Lei

    Highlights: Black-Right-Pointing-Pointer Vero cell-based HPAI H5N1 vaccine with stable high yield. Black-Right-Pointing-Pointer Stable high yield derived from the YNVa H3N2 backbone. Black-Right-Pointing-Pointer H5N1/YNVa has a similar safety and immunogenicity to H5N1delta. -- Abstract: Highly pathogenic avian influenza (HPAI) viruses pose a global pandemic threat, for which rapid large-scale vaccine production technology is critical for prevention and control. Because chickens are highly susceptible to HPAI viruses, the supply of chicken embryos for vaccine production might be depleted during a virus outbreak. Therefore, developing HPAI virus vaccines using other technologies is critical. Meeting vaccine demand using the Vero cell-based fermentation process hasmore » been hindered by low stability and yield. In this study, a Vero cell-based HPAI H5N1 vaccine candidate (H5N1/YNVa) with stable high yield was achieved by reassortment of the Vero-adapted (Va) high growth A/Yunnan/1/2005(H3N2) (YNVa) virus with the A/Anhui/1/2005(H5N1) attenuated influenza vaccine strain (H5N1delta) using the 6/2 method. The reassorted H5N1/YNVa vaccine maintained a high hemagglutination (HA) titer of 1024. Furthermore, H5N1/YNVa displayed low pathogenicity and uniform immunogenicity compared to that of the parent virus.« less

  8. H7N9 Influenza Virus Is More Virulent in Ferrets than 2009 Pandemic H1N1 Influenza Virus.

    PubMed

    Yum, Jung; Ku, Keun Bon; Kim, Hyun Soo; Seo, Sang Heui

    2015-12-01

    The novel H7N9 influenza virus has been infecting humans in China since February 2013 and with a mortality rate of about 40%. This study compared the pathogenicity of the H7N9 and 2009 pandemic H1N1 influenza viruses in a ferret model, which shows similar symptoms to those of humans infected with influenza viruses. The H7N9 influenza virus caused a more severe disease than did the 2009 pandemic H1N1 influenza virus. All of the ferrets infected with the H7N9 influenza virus had died by 6 days after infection, while none of those infected with the 2009 pandemic H1N1 influenza virus died. Ferrets infected with the H7N9 influenza virus had higher viral titers in their lungs than did those infected with the 2009 pandemic H1N1 influenza virus. Histological findings indicated that hemorrhagic pneumonia was caused by infection with the H7N9 influenza virus, but not with the 2009 pandemic H1N1 influenza virus. In addition, the lung tissues of ferrets infected with the H7N9 influenza virus contained higher levels of chemokines than did those of ferrets infected with the 2009 pandemic H1N1 influenza virus. This study suggests that close monitoring is needed to prevent human infection by the lethal H7N9 influenza virus.

  9. Determinants of Parental Acceptance of the H1N1 Vaccine

    ERIC Educational Resources Information Center

    Hilyard, Karen M.; Quinn, Sandra Crouse; Kim, Kevin H.; Musa, Don; Freimuth, Vicki S.

    2014-01-01

    Although designated as a high-risk group during the 2009-2010 H1N1 pandemic, only about 40% of U.S. children received the vaccine, a relatively low percentage compared with high-risk groups in seasonal influenza, such as the elderly, whose vaccine rates typically top 70%. To better understand parental decision making and predictors of acceptance…

  10. Impact of Body Mass Index on Immunogenicity of Pandemic H1N1 Vaccine in Children and Adults

    PubMed Central

    Callahan, S. Todd; Wolff, Mark; Hill, Heather R.; Edwards, Kathryn M.; Keitel, Wendy; Atmar, Robert; Patel, Shital; Sahly, Hana El; Munoz, Flor; Paul Glezen, W.; Brady, Rebecca; Frenck, Robert; Bernstein, David; Harrison, Christopher; Jackson, Mary Anne; Swanson, Douglas; Newland, Jason; Myers, Angela; Livingston, Robyn A; Walter, Emmanuel; Dolor, Rowena; Schmader, Kenneth; Mulligan, Mark J.; Edupuganti, Srilatha; Rouphael, Nadine; Whitaker, Jennifer; Spearman, Paul; Keyserling, Harry; Shane, Andi; Eckard, Allison Ross; Jackson, Lisa A.; Frey, Sharon E.; Belshe, Robert B.; Graham, Irene; Anderson, Edwin; Englund, Janet A.; Healy, Sara; Winokur, Patricia; Stapleton, Jack; Meier, Jeffrey; Kotloff, Karen; Chen, Wilbur; Hutter, Julia; Stephens, Ina; Wooten, Susan; Wald, Anna; Johnston, Christine; Edwards, Kathryn M.; Buddy Creech, C.; Todd Callahan, S.

    2014-01-01

    Obesity emerged as a risk factor for morbidity and mortality related to 2009 pandemic influenza A (H1N1) infection. However, few studies examine the immune responses to H1N1 vaccine among children and adults of various body mass indices (BMI). Pooling data from 3 trials of unadjuvanted split-virus H1N1 A/California/07/2009 influenza vaccines, we analyzed serologic responses of participants stratified by BMI grouping. A single vaccine dose produced higher hemagglutination inhibition antibody titers at day 21 in obese compared to nonobese adults, but there were no significant differences in responses to H1N1 vaccine among children or adults of various BMI following 2 doses. PMID:24795475

  11. Antibody Dynamics of 2009 Influenza A (H1N1) Virus in Infected Patients and Vaccinated People in China

    PubMed Central

    Liu, Yang; Wu, Jibin; Di, Biao; Chen, Xi; Xu, Xinhong; Lu, Enjie; Li, Kuibiao; Liu, Yanhui; Wu, Yejian; Chen, Xiongfei; He, Peng; Wang, Yulin; Liu, Jianhua

    2011-01-01

    Background To evaluate the risk of the recurrence and the efficiency of the vaccination, we followed-up antibody responses in patients with the 2009 pandemic H1N1 influenza and persons who received the pandemic H1N1 vaccine in Guangzhou China. Methods We collected serum samples from 129 patients and 86 vaccinated persons at day 0, 15, 30, 180 after the disease onset or the vaccination, respectively. Antibody titers in these serum samples were determined by haemagglutination inhibition (HI) assay using a local isolated virus strain A/Guangdong Liwan/SWL1538/2009(H1N1). Results HI antibody positive rate of the patients increased significantly from 0% to 60% at day 15 (χ2 = 78, P<0.001) and 100% at day 30 (χ2 = 23, P<0.001), but decreased significantly to 52% at day 180 (χ2 = 38, P<0.001), while that of vaccinated subjects increased from 0% to 78% at day 15 (χ2 = 110, P<0.001) and 81% at day 30 (χ2 = 0.32, P = 0.57), but decreased significantly to 34% at day 180 (χ2 = 39, P<0.001). Geometric mean titers (GMT) of HI antibodies in positive samples from the patients did not change significantly between day 15 and day 30 (T = 0.92, P = 0.36), but it decreased significantly from 80 at day 30 to 52 at day 180 (T = 4.5, P<0.001). GMT of vaccinated persons increased significantly from 100 at day 15 to 193 at day 30 (T = 4.5, P<0.001), but deceased significantly to 74 at day 180 (T = 5.1, P<0.001). Compared to the patients, the vaccinated subjects showed lower seroconversion rate (χ2 = 11, P<0.001; χ2 = 5.9, P = 0.015), but higher GMT (T = 6.0, P<0.001; T = 3.6, P = 0.001) at day 30 and day 180, respectively. Conclusion Vaccination of 2009 influenza A (H1N1) was effective. However, about half or more recovered patients and vaccinated persons might have lost sufficient immunity against the recurrence of the viral infection after half a year. Vaccination or re-vaccination may be necessary for

  12. Neurologic complications of influenza A(H1N1)pdm09

    PubMed Central

    Khandaker, Gulam; Zurynski, Yvonne; Buttery, Jim; Marshall, Helen; Richmond, Peter C.; Dale, Russell C.; Royle, Jenny; Gold, Michael; Snelling, Tom; Whitehead, Bruce; Jones, Cheryl; Heron, Leon; McCaskill, Mary; Macartney, Kristine; Elliott, Elizabeth J.

    2012-01-01

    Objective: We sought to determine the range and extent of neurologic complications due to pandemic influenza A (H1N1) 2009 infection (pH1N1′09) in children hospitalized with influenza. Methods: Active hospital-based surveillance in 6 Australian tertiary pediatric referral centers between June 1 and September 30, 2009, for children aged <15 years with laboratory-confirmed pH1N1′09. Results: A total of 506 children with pH1N1′09 were hospitalized, of whom 49 (9.7%) had neurologic complications; median age 4.8 years (range 0.5–12.6 years) compared with 3.7 years (0.01–14.9 years) in those without complications. Approximately one-half (55.1%) of the children with neurologic complications had preexisting medical conditions, and 42.8% had preexisting neurologic conditions. On presentation, only 36.7% had the triad of cough, fever, and coryza/runny nose, whereas 38.7% had only 1 or no respiratory symptoms. Seizure was the most common neurologic complication (7.5%). Others included encephalitis/encephalopathy (1.4%), confusion/disorientation (1.0%), loss of consciousness (1.0%), and paralysis/Guillain-Barré syndrome (0.4%). A total of 30.6% needed intensive care unit (ICU) admission, 24.5% required mechanical ventilation, and 2 (4.1%) died. The mean length of stay in hospital was 6.5 days (median 3 days) and mean ICU stay was 4.4 days (median 1.5 days). Conclusions: Neurologic complications are relatively common among children admitted with influenza, and can be life-threatening. The lack of specific treatment for influenza-related neurologic complications underlines the importance of early diagnosis, use of antivirals, and universal influenza vaccination in children. Clinicians should consider influenza in children with neurologic symptoms even with a paucity of respiratory symptoms. PMID:22993280

  13. Vaccination with NS1-truncated H3N2 swine influenza virus primes T cells and confers cross-protection against an H1N1 heterosubtypic challenge in pigs

    USDA-ARS?s Scientific Manuscript database

    The diversity of contemporary swine influenza virus (SIV) strains impedes effective immunization of swine herds. Mucosally delivered, attenuated virus vaccines are one approach with potential to provide broad cross-protection. Reverse genetics-derived H3N2 SIV virus with truncated NS1 (NS1delta126 T...

  14. Comparative safety, immunogenicity, and efficacy of several anti-H5N1 influenza experimental vaccines in a mouse and chicken models (Testing of killed and live H5 vaccine).

    PubMed

    Gambaryan, Alexandra S; Lomakina, Natalia F; Boravleva, Elizaveta Y; Kropotkina, Ekaterina A; Mashin, Vadim V; Krasilnikov, Igor V; Klimov, Alexander I; Rudenko, Larisa G

    2012-05-01

    Parallel testing of inactivated (split and whole virion) and live vaccine was conducted to compare the immunogenicity and protective efficacy against homologous and heterosubtypic challenge by H5N1 highly pathogenic avian influenza virus. Four experimental live vaccines based on two H5N1 influenza virus strains were tested; two of them had hemagglutinin (HA) of A/Vietnam/1203/04 strain lacking the polybasic HA cleavage site, and two others had hemagglutinins from attenuated H5N1 virus A/Chicken/Kurgan/3/05, with amino acid substitutions of Asp54/Asn and Lys222/Thr in HA1 and Val48/Ile and Lys131/Thr in HA2 while maintaining the polybasic HA cleavage site. The neuraminidase and non-glycoprotein genes of the experimental live vaccines were from H2N2 cold-adapted master strain A/Leningrad/134/17/57 (VN-Len and Ku-Len) or from the apathogenic H6N2 virus A/Gull/Moscow/3100/2006 (VN-Gull and Ku-Gull). Inactivated H5N1 and H1N1 and live H1N1 vaccine were used for comparison. All vaccines were applied in a single dose. Safety, immunogenicity, and protectivity against the challenge with HPAI H5N1 virus A/Chicken/Kurgan/3/05 were estimated. All experimental live H5 vaccines tested were apathogenic as determined by weight loss and conferred more than 90% protection against lethal challenge with A/Chicken/Kurgan/3/05 infection. Inactivated H1N1 vaccine in mice offered no protection against challenge with H5N1 virus, while live cold-adapted H1N1 vaccine reduced the mortality near to zero level. The high yield, safety, and protectivity of VN-Len and Ku-Len made them promising strains for the production of inactivated and live vaccines against H5N1 viruses. © 2011 Blackwell Publishing Ltd.

  15. Immunogenicity and safety of two doses of a non-adjuvanted influenza A H1N1/2009 vaccine in young autoimmune rheumatic diseases patients.

    PubMed

    Aikawa, N E; Trudes, G; Campos, L M A; Pereira, R M R; Moraes, J C B; Ribeiro, A C; Miraglia, J; Timenetsky, M do Carmo S; Bonfa, E; Silva, Ca

    2013-11-01

    The aim of this study was to evaluate the immunogenicity and safety of the influenza A H1N1/2009 vaccine in children under 9 years old with autoimmune rheumatic diseases (ARD). Thirty-eight ARD patients and 11 healthy children received two doses of non-adjuvanted influenza A/California/7/2009 (H1N1) virus-like vaccine. Subjects were evaluated before and 21 days after vaccination. Seroprotection (SP) and seroconversion (SC) rates, geometric mean titers (GMT) and factor increases (FI) in GMT were calculated. Mean ages were comparable between patients and controls. Pre-vaccination SP and GMT were similar in patients and controls (p > 0.05). Three weeks after immunization, SP (81.6% vs. 81.8%, p = 1.0), SC (81.6% vs. 90.9%, p = 0.66), GMT (151.5 vs. 282.1, p = 0.26) and the FI in GMT (16.7 vs. 36.3, p = 0.23) were similar in patients and controls, with both groups achieving an adequate response, according to the European Medicines Agency and Food and Drug Administration standards. Analysis of the possible factors influencing SC showed no difference in demographic data, leukocyte/lymphocyte counts or immunosuppressant use between seroconverted and non-seroconverted patients (p > 0.05). The vaccine demonstrated a satisfactory safety profile in this population. Two doses of influenza A H1N1/2009 vaccination induced an effective antibody response and caused adverse events in rare instances, suggesting this vaccine is appropriate and can be recommended for this age group.

  16. Protective effect of A/H1N1 vaccination in immune-mediated disease--a prospectively controlled vaccination study.

    PubMed

    Adler, Sabine; Krivine, Anne; Weix, Janine; Rozenberg, Flore; Launay, Odile; Huesler, Juerg; Guillevin, Loïc; Villiger, Peter M

    2012-04-01

    To assess the 2009 influenza vaccine A/H1N1 on antibody response, side effects and disease activity in patients with immune-mediated diseases. Patients with RA, SpA, vasculitis (VAS) or CTD (n = 149) and healthy individuals (n = 40) received a single dose of adjuvanted A/H1N1 influenza vaccine. Sera were obtained before vaccination, and 3 weeks, 6 weeks and 6 months thereafter. A/H1N1 antibody titres were measured by haemagglutination inhibition (HAI) assay. Seroprotection was defined as specific antibody titre ≥ 1 : 40, seroconversion as 4-fold increase in antibody titre. Titres increased significantly in patients and controls with a maximum at Week 3, declining to levels below protection at Month 6 (P < 0.001). Seroprotection was more frequently reached in SpA and CTD than in RA and VAS (80 and 82% and 57 and 47%, respectively). There was a significantly negative impact by MTX (P < 0.001), rituximab (P = 0.0031) and abatacept (P = 0.045). Other DMARDs, glucocorticoids and TNF blockers did not significantly suppress response (P = 0.06, 0.11 and 0.81, respectively). A linear decline in response was noted in patients with increasing age (P < 0.001). Disease reactivation possibly related to vaccination was suspected in 8/149 patients. No prolonged side effects or A/H1N1 infections were noted. The results show that vaccination response is a function of disease type, intensity and character of medication and age. A single injection of adjuvanted influenza vaccine is sufficient to protect a high percentage of patients. Therefore, differential vaccination recommendations might in the future reduce costs and increase vaccination acceptance.

  17. Stockpiled pre-pandemic H5N1 influenza virus vaccines with AS03 adjuvant provide cross-protection from H5N2 clade 2.3.4.4 virus challenge in ferrets

    PubMed Central

    Sun, Xiangjie; Belser, Jessica A.; Pulit-Penaloza, Joanna A.; Creager, Hannah M.; Guo, Zhu; Jefferson, Stacie N.; Liu, Feng; York, Ian A.; Stevens, James; Maines, Taronna R.; Jernigan, Daniel B.; Katz, Jacqueline M.; Levine, Min Z.; Tumpey, Terrence M.

    2018-01-01

    Avian influenza viruses, notably H5 subtype viruses, pose a continuous threat to public health due to their pandemic potential. In recent years, influenza virus H5 subtype split vaccines with novel oil-in-water emulsion based adjuvants (e.g. AS03, MF59) have been shown to be safe, immunogenic, and able to induce broad immune responses in clinical trials, providing strong scientific support for vaccine stockpiling. However, whether such vaccines can provide protection from infection with emerging, antigenically distinct clades of H5 viruses has not been adequately addressed. Here, we selected two AS03-adjuvanted H5N1 vaccines from the US national prepandemic influenza vaccine stockpile and assessed whether the 2004–05 vaccines could provide protection against a 2014 highly pathogenic avian influenza (HPAI) H5N2 virus (A/northern pintail/Washington/40964/2014), a clade 2.3.4.4 virus responsible for mass culling of poultry in North America. Ferrets received two doses of adjuvanted vaccine containing 7.5 μg of hemagglutinin (HA) from A/Vietnam/1203/2004 (clade 1) or A/Anhui/1/2005 (clade 2.3.4) virus either in a homologous or heterologous prime-boost vaccination regime. We found that both vaccination regimens elicited robust antibody responses against the 2004–05 vaccine viruses and could reduce virus-induced morbidity and viral replication in the lower respiratory tract upon heterologous challenge despite the low level of cross-reactive antibody titers to the challenge H5N2 virus. This study supports the value of existing stockpiled 2004–05 influenza H5N1 vaccines, combined with AS03-adjuvant for early use in the event of an emerging pandemic with H5N2-like clade 2.3.4.4 viruses. PMID:28554058

  18. Importance of background rates of disease in assessment of vaccine safety during mass immunisation with pandemic H1N1 influenza vaccines

    PubMed Central

    Black, Steven; Eskola, Juhani; Siegrist, Claire-Anne; Halsey, Neal; MacDonald, Noni; Law, Barbara; Miller, Elizabeth; Andrews, Nick; Stowe, Julia; Salmon, Daniel; Vannice, Kirsten; Izurieta, Hector S; Akhtar, Aysha; Gold, Mike; Oselka, Gabriel; Zuber, Patrick; Pfeifer, Dina; Vellozzi, Claudia

    2010-01-01

    Because of the advent of a new influenza A H1N1 strain, many countries have begun mass immunisation programmes. Awareness of the background rates of possible adverse events will be a crucial part of assessment of possible vaccine safety concerns and will help to separate legitimate safety concerns from events that are temporally associated with but not caused by vaccination. We identified background rates of selected medical events for several countries. Rates of disease events varied by age, sex, method of ascertainment, and geography. Highly visible health conditions, such as Guillain-Barré syndrome, spontaneous abortion, or even death, will occur in coincident temporal association with novel influenza vaccination. On the basis of the reviewed data, if a cohort of 10 million individuals was vaccinated in the UK, 21·5 cases of Guillain-Barré syndrome and 5·75 cases of sudden death would be expected to occur within 6 weeks of vaccination as coincident background cases. In female vaccinees in the USA, 86·3 cases of optic neuritis per 10 million population would be expected within 6 weeks of vaccination. 397 per 1 million vaccinated pregnant women would be predicted to have a spontaneous abortion within 1 day of vaccination. PMID:19880172

  19. Immunogenicity and Safety of a Trivalent Inactivated Influenza Vaccine in Children 6 Months to 17 Years of Age, Previously Vaccinated with an AS03-Adjuvanted A(H1N1)Pdm09 Vaccine: Two Open-label, Randomized Trials.

    PubMed

    Vesikari, Timo; Richardus, Jan Hendrik; Berglund, Johan; Korhonen, Tiina; Flodmark, Carl-Erik; Lindstrand, Ann; Silfverdal, Sven Arne; Bambure, Vinod; Caplanusi, Adrian; Dieussaert, Ilse; Roy-Ghanta, Sumita; Vaughn, David W

    2015-07-01

    During the influenza pandemic 2009-2010, an AS03-adjuvanted A(H1N1)pdm09 vaccine was used extensively in children 6 months of age and older, and during the 2010-2011 influenza season, the A(H1N1)pdm09 strain was included in the seasonal trivalent inactivated influenza vaccine (TIV) without adjuvant. We evaluated the immunogenicity and safety of TIV in children previously vaccinated with the AS03-adjuvanted A(H1N1)pdm09 vaccine. Healthy children were randomized (1:1) to receive TIV or a control vaccine. Children were aged 6 months to 9 years (n = 154) and adolescents 10-17 years (n = 77) when they received AS03-adjuvanted A(H1N1)pdm09 vaccine at least 6 months before study enrolment. Hemagglutination inhibition (HI) and neutralizing antibody responses against the A(H1N1)pdm09 strain were evaluated before (day 0) and at day 28 and month 6 after study vaccination. Reactogenicity was assessed during the 7 day postvaccination period, and safety was assessed for 6 months. At day 0, >93.9% of all children had HI titers ≥1:40 for the A(H1N1)pdm09 strain, which increased to 100% at both day 28 and month 6 in the TIV group. Between days 0 and 28, HI antibody geometric mean titers against A(H1N1)pdm09 increased by 9-fold and 4-fold in children 6 months to 9 years of age and 10-17 years of age, respectively. AS03-adjuvanted A(H1N1)pdm09 vaccine-induced robust immune responses in children that persisted into the next season, yet were still boosted by TIV containing A(H1N1)pdm09. The reactogenicity and safety profile of TIV did not appear compromised by prior receipt of AS03-adjuvanted A(H1N1)pdm09 vaccine.

  20. The responses of Aboriginal Canadians to adjuvanted pandemic (H1N1) 2009 influenza vaccine

    PubMed Central

    Rubinstein, Ethan; Predy, Gerald; Sauvé, Laura; Hammond, Greg W.; Aoki, Fred; Sikora, Chris; Li, Yan; Law, Barbara; Halperin, Scott; Scheifele, David

    2011-01-01

    Background: Because many Aboriginal Canadians had severe cases of pandemic (H1N1) 2009 influenza, they were given priority access to vaccine. However, it was not known if the single recommended dose would adequately protect people at high risk, prompting our study to assess responses to the vaccine among Aboriginal Canadians. Methods: We enrolled First Nations and Métis adults aged 20–59 years in our prospective cohort study. Participants were given one 0.5-mL dose of ASO3-adjuvanted pandemic (H1N1) 2009 vaccine (Arepanrix, GlaxoSmithKline Canada). Blood samples were taken at baseline and 21–28 days after vaccination. Paired sera were tested for hemagglutination-inhibiting antibodies at a reference laboratory. To assess vaccine safety, we monitored the injection site symptoms of each participant for seven days. We also monitored patients for general symptoms within 7 days of vaccination and any use of the health care system for 21–28 days after vaccination. Results: We enrolled 138 participants in the study (95 First Nations, 43 Métis), 137 of whom provided all safety data and 136 of whom provided both blood samples. First Nations and Métis participants had similar characteristics, including high rates of chronic health conditions (74.4%–76.8%). Pre-existing antibody to the virus was detected in 34.3% of the participants, all of whom boosted strongly with vaccination (seroprotection rate [titre ≥ 40] 100%, geometric mean titre 531–667). Particpants with no pre-existing antibody also responded well. Fifty-eight of 59 (98.3%) First Nations participants showed seroprotection and a geometric mean titre of 353.6; all 30 Métis participants with no pre-existing antibody showed seroprotection and a geometric mean titre of 376.2. Pain at the injection site and general symptoms frequently occurred but were short-lived and generally not severe, although three participants (2.2%) sought medical attention for general symptoms. Interpretation: First Nations and

  1. Where are we in our understanding of the association between narcolepsy and one of the 2009 adjuvanted influenza A (H1N1) vaccines?

    PubMed

    Johansen, K; Brasseur, D; MacDonald, N; Nohynek, H; Vandeputte, J; Wood, D; Neels, P

    2016-07-01

    Evaluating new rare serious vaccine safety signals is difficult and complex work. To further assess the observed increase in narcolepsy cases seen in Europe with the 2009 pandemic H1N1 influenza vaccine, the International Alliance for Biological Standardization (IABS) invited a wide range of experts to a one day meeting in Geneva in October 2015 to present data and to discuss the implications. The presentations covered the following topics: clinical picture of childhood narcolepsy following the 2009 H1N1 pandemic vaccination campaigns; epidemiological studies conducted to assess the risk of narcolepsy, other neurological and immune-related diseases following 2009 pandemic H1N1 influenza vaccine; potential biases influencing the different epidemiological study designs; potential genetic contribution to the development of narcolepsy; potential biological mechanisms for development of narcolepsy in this setting including the role of the virus itself, antigenic differences between the vaccines and differences in AS03-adjuvanted vaccines. The presentations were followed by fulsome roundtable discussions. Members from affected families also attended and made informal comments to round out the day's deliberations. This meeting emphasized the value added in bringing together in a neutral setting a wide range of experts and vaccine producers to discuss such a complex new serious adverse event following immunization. Copyright © 2016.

  2. Isolation of avian influenza H5N1 virus from vaccinated commercial layer flock in Egypt

    PubMed Central

    2012-01-01

    Background Uninterrupted transmission of highly pathogenic avian influenza virus (HPAIV) H5N1 of clade 2.2.1 in Egypt since 2006 resulted in establishment of two main genetic clusters. The 2.2.1/C group where all recent human and majority of backyard origin viruses clustered together, meanwhile the majority of viruses derived from vaccinated poultry in commercial farms grouped in 2.2.1.1 clade. Findings In the present investigation, an HPAIV H5N1 was isolated from twenty weeks old layers chickens that were vaccinated with a homologous H5N1 vaccine at 1, 7 and 16 weeks old. At twenty weeks of age, birds showed cyanosis of comb and wattle, decrease in egg production and up to 27% mortality. Examined serum samples showed low antibody titer in HI test (Log2 3.2± 4.2). The hemagglutinin (HA) and neuraminidase (NA) genes of the isolated virus were closely related to viruses in 2.2.1/C group isolated from poultry in live bird market (LBM) and backyards or from infected people. Conspicuous mutations in the HA and NA genes including a deletion within the receptor binding domain in the HA globular head region were observed. Conclusions Despite repeated vaccination of layer chickens using a homologous H5N1 vaccine, infection with HPAIV H5N1 resulted in significant morbidity and mortality. In endemic countries like Egypt, rigorous control measures including enforcement of biosecurity, culling of infected birds and constant update of vaccine virus strains are highly required to prevent circulation of HPAIV H5N1 between backyard birds, commercial poultry, LBM and humans. PMID:23185975

  3. The European I-MOVE Multicentre 2013-2014 Case-Control Study. Homogeneous moderate influenza vaccine effectiveness against A(H1N1)pdm09 and heterogenous results by country against A(H3N2).

    PubMed

    Valenciano, Marta; Kissling, Esther; Reuss, Annicka; Jiménez-Jorge, Silvia; Horváth, Judit K; Donnell, Joan M O; Pitigoi, Daniela; Machado, Ausenda; Pozo, Francisco

    2015-06-04

    In the first five I-MOVE (Influenza Monitoring Vaccine Effectiveness in Europe) influenza seasons vaccine effectiveness (VE) results were relatively homogenous among participating study sites. In 2013-2014, we undertook a multicentre case-control study based on sentinel practitioner surveillance networks in six European Union (EU) countries to measure 2013-2014 influenza VE against medically-attended influenza-like illness (ILI) laboratory-confirmed as influenza. Influenza A(H3N2) and A(H1N1)pdm09 viruses co-circulated during the season. Practitioners systematically selected ILI patients to swab within eight days of symptom onset. We compared cases (ILI positive to influenza A(H3N2) or A(H1N1)pdm09) to influenza negative patients. We calculated VE for the two influenza A subtypes and adjusted for potential confounders. We calculated heterogeneity between sites using the I(2) index and Cochrane's Q test. If the I(2) was <50%, we estimated pooled VE as (1 minus the OR)×100 using a one-stage model with study site as a fixed effect. If the I(2) was >49% we used a two-stage random effects model. We included in the A(H1N1)pdm09 analysis 531 cases and 1712 controls and in the A(H3N2) analysis 623 cases and 1920 controls. For A(H1N1)pdm09, the Q test (p=0.695) and the I(2) index (0%) suggested no heterogeneity of adjusted VE between study sites. Using a one-stage model, the overall pooled adjusted VE against influenza A(H1N1)pdm2009 was 47.5% (95% CI: 16.4-67.0). For A(H3N2), the I(2) was 51.5% (p=0.067). Using a two-stage model for the pooled analysis, the adjusted VE against A(H3N2) was 29.7 (95% CI: -34.4-63.2). The results suggest a moderate 2013-2014 influenza VE against A(H1N1)pdm09 and a low VE against A(H3N2). The A(H3N2) estimates were heterogeneous among study sites. Larger sample sizes by study site are needed to prevent statistical heterogeneity, decrease variability and allow for two-stage pooled VE for all subgroup analyses. Copyright © 2015 The Authors

  4. Seroprevalence of influenza A H1N1 and seroconversion of mothers and infants induced by a single dose of monovalent vaccine.

    PubMed

    Chao, Anne; Huang, Yhu-Chering; Chang, Yao-Lung; Wang, Tzu-Hao; Chang, Shuenn-Dyh; Wu, Ting-Shu; Wu, Tsu-Lan; Chao, An-Shine

    2013-09-01

    To determine the prevalence of preexisting antibodies against the pandemic 2009 Influenza A (H1N1) virus in pregnant women and to evaluate the seroprotection of the mothers and infants by a single injection of monovalent vaccine during the pandemic. Seropositivity rate of H1N1 among the nonvaccinated were compared with the vaccinated women. A single dose of vaccine, either nonadjuvanted AdimFlu-S or MF59-adjuvanted vaccine, was injected to the voluntarily vaccinated group. Maternal and cord blood sera were collected to evaluate the antibody response of the H1N1 virus. Seropositivity was defined as a hemagglutination inhibition titer to H1N1 (A/Taiwan/126/09) ≥ 1:40. A total of 210 healthy, singleton, pregnant women were enrolled between January 2010 and May 2010. Seropositivity (≥ 1:40) of maternal hemagglutination inhibition was significantly higher in the vaccinated group (78%) than the nonvaccinated group (9.5%); 41.6% (20/48) of seropositive titers were >1:80. In nine vaccinated cases resulting in negative serum titers (<1:40), the prevalence of negative titer in the women received AdimFlu-S (14.8%, 4/31) was lower (p = 0.025) than those received MF59-adjuvanted vaccine (50%, 5/10). Subclinical infection against H1N1 was low in Taiwanese pregnant women in the pandemic 2009. Seropositivity >75% could be achieved in the paired maternal and cord serum samples by a single injection of monovalent H1N1 vaccine. Copyright © 2013. Published by Elsevier B.V.

  5. A novel H6N1 virus-like particle vaccine induces long-lasting cross-clade antibody immunity against human and avian H6N1 viruses.

    PubMed

    Yang, Ji-Rong; Chen, Chih-Yuan; Kuo, Chuan-Yi; Cheng, Chieh-Yu; Lee, Min-Shiuh; Cheng, Ming-Chu; Yang, Yu-Chih; Wu, Chia-Ying; Wu, Ho-Sheng; Liu, Ming-Tsan; Hsiao, Pei-Wen

    2016-02-01

    Avian influenza A(H6N1) virus is one of the most common viruses isolated from migrating birds and domestic poultry in many countries. The first and only known case of human infection by H6N1 virus in the world was reported in Taiwan in 2013. This led to concern that H6N1 virus may cause a threat to public health. In this study, we engineered a recombinant H6N1 virus-like particle (VLP) and investigated its vaccine effectiveness compared to the traditional egg-based whole inactivated virus (WIV) vaccine. The H6N1-VLPs exhibited similar morphology and functional characteristics to influenza viruses. Prime-boost intramuscular immunization in mice with unadjuvanted H6N1-VLPs were highly immunogenic and induced long-lasting antibody immunity. The functional activity of the VLP-elicited IgG antibodies was proved by in vitro seroprotective hemagglutination inhibition and microneutralization titers against the homologous human H6N1 virus, as well as in vivo viral challenge analyses which showed H6N1-VLP immunization significantly reduced viral load in the lung, and protected against human H6N1 virus infection. Of particular note, the H6N1-VLPs but not the H6N1-WIVs were able to confer cross-reactive humoral immunity; antibodies induced by H6N1-VLP vaccine robustly inhibited the hemagglutination activities and in vitro replication of distantly-related heterologous avian H6N1 viruses. Furthermore, the H6N1-VLPs were found to elicit significantly greater anti-HA2 antibody responses in immunized mice than H6N1-WIVs. Collectively, we demonstrated for the first time a novel H6N1-VLP vaccine that effectively provides broadly protective immunity against both human and avian H6N1 viruses. These results, which uncover the underlying mechanisms for induction of wide-range immunity against influenza viruses, may be useful for future influenza vaccine development. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. The safety of the H1N1 influenza A vaccine in egg allergic individuals.

    PubMed

    Greenhawt, Matthew J; Chernin, Anna S; Howe, Laura; Li, James T; Sanders, Georgiana

    2010-11-01

    The safety of H1N1 vaccine is unknown in egg allergic (EA) recipients. To establish the safety of administering H1N1 vaccine and to evaluate the predictability of H1N1 skin testing in EA patients. In a controlled, prospective trial, H1N1 skin testing and vaccination was compared between EA patients (n = 105) and non-EA controls (n = 19). Those with negative H1N1 skin test results received a full H1N1 dose; those with a positive skin test result received a graded challenge (10%, 90%). Booster vaccine, if required, was given as a single dose from a different lot without prior testing. Prick and intradermal test results were positive in 3 (2.4%) of 124 and 41 (33.1%) of 124 study participants, respectively. Forty-one individuals received a 2-step graded vaccine challenge, including 13 of 25 with a history of egg anaphylaxis. No significant allergic reactions resulted from either method of vaccination or from subsequent booster doses. All study participants received the H1N1 vaccine without significant allergic reactions. Skin testing is unnecessary and does not predict vaccine tolerance. All study participants who received a graded challenge tolerated a single dose booster from a different, untested lot, including 7 individuals with a history of egg-induced anaphylaxis. We recommend administration of H1N1 vaccine to EA children without prior skin testing or graded challenge dosing. Copyright © 2010 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  7. Suboptimal protection against H5N1 highly pathogenic avian influenza viruses from Vietnam in ducks vaccinated with commercial poultry vaccines

    USDA-ARS?s Scientific Manuscript database

    Highly pathogenic (HP) H5N1 avian influenza (AI) viruses continue to circulate in Asia and other regions of the world. Vaccination is used as part of H5N1 HPAI control programs in many countries; however, eradication of the disease has not been possible due to the emergence and spread of new viruses...

  8. Experimental transmission of avian-like swine H1N1 influenza virus between immunologically naïve and vaccinated pigs.

    PubMed

    Lloyd, Lucy E; Jonczyk, Magdalena; Jervis, Carley M; Flack, Deborah J; Lyall, John; Foote, Alasdair; Mumford, Jennifer A; Brown, Ian H; Wood, James L; Elton, Debra M

    2011-09-01

    Infection of pigs with swine influenza has been studied experimentally and in the field; however, little information is available on the natural transmission of this virus in pigs. Two studies in an experimental transmission model are presented here, one in immunologically naïve and one in a combination of vaccinated and naïve pigs. To investigate the transmission of a recent 'avian-like' swine H1N1 influenza virus in naive piglets, to assess the antibody response to a commercially available vaccine and to determine the efficiency of transmission in pigs after vaccination. Transmission chains were initiated by intranasal challenge of two immunologically naïve pigs. Animals were monitored daily for clinical signs and virus shedding. Pairs of pigs were sequentially co-housed, and once virus was detected in recipients, prior donors were removed. In the vaccination study, piglets were vaccinated and circulating antibody levels were monitored by haemagglutination inhibition assay. To study transmission in vaccinates, a pair of infected immunologically naïve animals was co-housed with vaccinated recipient pigs and further pairs of vaccinates were added sequentially as above. The chain was completed by the addition of naive pigs. Transmission of the H1N1 virus was achieved through a chain of six pairs of naïve piglets and through four pairs of vaccinated animals. Transmission occurred with minimal clinical signs and, in vaccinates, at antibody levels higher than previously reported to protect against infection. © 2011 Blackwell Publishing Ltd.

  9. Cell-Based Systems Biology Analysis of Human AS03-Adjuvanted H5N1 Avian Influenza Vaccine Responses: A Phase I Randomized Controlled Trial.

    PubMed

    Howard, Leigh M; Hoek, Kristen L; Goll, Johannes B; Samir, Parimal; Galassie, Allison; Allos, Tara M; Niu, Xinnan; Gordy, Laura E; Creech, C Buddy; Prasad, Nripesh; Jensen, Travis L; Hill, Heather; Levy, Shawn E; Joyce, Sebastian; Link, Andrew J; Edwards, Kathryn M

    2017-01-01

    Vaccine development for influenza A/H5N1 is an important public health priority, but H5N1 vaccines are less immunogenic than seasonal influenza vaccines. Adjuvant System 03 (AS03) markedly enhances immune responses to H5N1 vaccine antigens, but the underlying molecular mechanisms are incompletely understood. We compared the safety (primary endpoint), immunogenicity (secondary), gene expression (tertiary) and cytokine responses (exploratory) between AS03-adjuvanted and unadjuvanted inactivated split-virus H5N1 influenza vaccines. In a double-blinded clinical trial, we randomized twenty adults aged 18-49 to receive two doses of either AS03-adjuvanted (n = 10) or unadjuvanted (n = 10) H5N1 vaccine 28 days apart. We used a systems biology approach to characterize and correlate changes in serum cytokines, antibody titers, and gene expression levels in six immune cell types at 1, 3, 7, and 28 days after the first vaccination. Both vaccines were well-tolerated. Nine of 10 subjects in the adjuvanted group and 0/10 in the unadjuvanted group exhibited seroprotection (hemagglutination inhibition antibody titer > 1:40) at day 56. Within 24 hours of AS03-adjuvanted vaccination, increased serum levels of IL-6 and IP-10 were noted. Interferon signaling and antigen processing and presentation-related gene responses were induced in dendritic cells, monocytes, and neutrophils. Upregulation of MHC class II antigen presentation-related genes was seen in neutrophils. Three days after AS03-adjuvanted vaccine, upregulation of genes involved in cell cycle and division was detected in NK cells and correlated with serum levels of IP-10. Early upregulation of interferon signaling-related genes was also found to predict seroprotection 56 days after first vaccination. Using this cell-based systems approach, novel mechanisms of action for AS03-adjuvanted pandemic influenza vaccination were observed. ClinicalTrials.gov NCT01573312.

  10. Live attenuated pandemic influenza vaccine: clinical studies on A/17/California/2009/38 (H1N1) and licensing of the Russian-developed technology to WHO for pandemic influenza preparedness in developing countries.

    PubMed

    Rudenko, Larisa; van den Bosch, Han; Kiseleva, Irina; Mironov, Alexander; Naikhin, Anatoly; Larionova, Natalie; Bushmenkov, Dimitry

    2011-07-01

    In February 2009, Nobilon granted the World Health Organization (WHO) a non-exclusive licence to develop, register, manufacture, use and sell seasonal a pandemic live attenuated influenza vaccine (LAIV) produced on embryonated chicken eggs. WHO was permitted to grant sub-licences to vaccine manufacturers in developing countries within the framework of its influenza vaccine technology transfer initiative. In parallel, the Institute of Experimental Medicine (IEM), Russia, concluded an agreement with WHO for the supply of Russian LAIV reassortants for use by these manufacturers. Also in 2009, IEM carried out a study on a novel A/17/California/2009/38 (H1N1) pandemic LAIV candidate derived from the pandemic-related A/California/07/2009 (H1N1) influenza virus and the attenuated A/Leningrad/134/17/57 (H2N2) master donor virus, using routine reassortant technique in embryonated chicken eggs. Following successful preclinical studies in eggs and in ferrets, a double-blind, controlled, randomized clinical trial was carried out in immunologically naïve study participants between 12-18 and 18-60 years old. Collectively, the immunogenicity data (haemagglutinin inhibition test, ELISA and cytokine tests for the detection of memory T cells) support the use of a single dose of the pandemic H1N1 LAIV in 12-60 year olds. The outcome of the studies showed no significant adverse reactions attributable to the vaccine, and suggests that the vaccine is as safe and immunogenic as seasonal influenza vaccines. Importantly, it was clearly demonstrated that reliance on the HAI assay alone is not recommended for testing LAIV. To date, via the licence agreement with WHO, the H1N1 LAIV has been transferred to the Government Pharmaceutical Organization in Thailand, the Serum Institute of India, and the Zhejiang Tianyuan Bio-Pharmaceutical Co., Ltd. in China. Copyright © 2011 Elsevier Ltd. All rights reserved.

  11. In Silico Identification of Highly Conserved Epitopes of Influenza A H1N1, H2N2, H3N2, and H5N1 with Diagnostic and Vaccination Potential

    PubMed Central

    Muñoz-Medina, José Esteban; Sánchez-Vallejo, Carlos Javier; Méndez-Tenorio, Alfonso; Monroy-Muñoz, Irma Eloísa; Angeles-Martínez, Javier; Santos Coy-Arechavaleta, Andrea; Santacruz-Tinoco, Clara Esperanza; González-Ibarra, Joaquín; Anguiano-Hernández, Yu-Mei; González-Bonilla, César Raúl; Ramón-Gallegos, Eva; Díaz-Quiñonez, José Alberto

    2015-01-01

    The unpredictable, evolutionary nature of the influenza A virus (IAV) is the primary problem when generating a vaccine and when designing diagnostic strategies; thus, it is necessary to determine the constant regions in viral proteins. In this study, we completed an in silico analysis of the reported epitopes of the 4 IAV proteins that are antigenically most significant (HA, NA, NP, and M2) in the 3 strains with the greatest world circulation in the last century (H1N1, H2N2, and H3N2) and in one of the main aviary subtypes responsible for zoonosis (H5N1). For this purpose, the HMMER program was used to align 3,016 epitopes reported in the Immune Epitope Database and Analysis Resource (IEDB) and distributed in 34,294 stored sequences in the Pfam database. Eighteen epitopes were identified: 8 in HA, 5 in NA, 3 in NP, and 2 in M2. These epitopes have remained constant since they were first identified (~91 years) and are present in strains that have circulated on 5 continents. These sites could be targets for vaccination design strategies based on epitopes and/or as markers in the implementation of diagnostic techniques. PMID:26346523

  12. Association between the 2008–09 Seasonal Influenza Vaccine and Pandemic H1N1 Illness during Spring–Summer 2009: Four Observational Studies from Canada

    PubMed Central

    Skowronski, Danuta M.; De Serres, Gaston; Crowcroft, Natasha S.; Janjua, Naveed Z.; Boulianne, Nicole; Hottes, Travis S.; Rosella, Laura C.; Dickinson, James A.; Gilca, Rodica; Sethi, Pam; Ouhoummane, Najwa; Willison, Donald J.; Rouleau, Isabelle; Petric, Martin; Fonseca, Kevin; Drews, Steven J.; Rebbapragada, Anuradha; Charest, Hugues; Hamelin, Marie-Ève; Boivin, Guy; Gardy, Jennifer L.; Li, Yan; Kwindt, Trijntje L.; Patrick, David M.; Brunham, Robert C.

    2010-01-01

    Background In late spring 2009, concern was raised in Canada that prior vaccination with the 2008–09 trivalent inactivated influenza vaccine (TIV) was associated with increased risk of pandemic influenza A (H1N1) (pH1N1) illness. Several epidemiologic investigations were conducted through the summer to assess this putative association. Methods and Findings Studies included: (1) test-negative case-control design based on Canada's sentinel vaccine effectiveness monitoring system in British Columbia, Alberta, Ontario, and Quebec; (2) conventional case-control design using population controls in Quebec; (3) test-negative case-control design in Ontario; and (4) prospective household transmission (cohort) study in Quebec. Logistic regression was used to estimate odds ratios for TIV effect on community- or hospital-based laboratory-confirmed seasonal or pH1N1 influenza cases compared to controls with restriction, stratification, and adjustment for covariates including combinations of age, sex, comorbidity, timeliness of medical visit, prior physician visits, and/or health care worker (HCW) status. For the prospective study risk ratios were computed. Based on the sentinel study of 672 cases and 857 controls, 2008–09 TIV was associated with statistically significant protection against seasonal influenza (odds ratio 0.44, 95% CI 0.33–0.59). In contrast, estimates from the sentinel and three other observational studies, involving a total of 1,226 laboratory-confirmed pH1N1 cases and 1,505 controls, indicated that prior receipt of 2008–09 TIV was associated with increased risk of medically attended pH1N1 illness during the spring–summer 2009, with estimated risk or odds ratios ranging from 1.4 to 2.5. Risk of pH1N1 hospitalization was not further increased among vaccinated people when comparing hospitalized to community cases. Conclusions Prior receipt of 2008–09 TIV was associated with increased risk of medically attended pH1N1 illness during the spring

  13. Characterization and long-term persistence of immune response following two doses of an AS03A-adjuvanted H1N1 influenza vaccine in healthy Japanese adults.

    PubMed

    Ikematsu, Hideyuki; Nagai, Hideaki; Kawashima, Masahiro; Kawakami, Yasunobu; Tenjinbaru, Kazuyoshi; Li, Ping; Walravens, Karl; Gillard, Paul; Roman, François

    2012-02-01

    Background Long-term persistence of immune response and safety of two doses of an A/California/07/2009 H1N1 pandemic influenza vaccine adjuvanted with AS03 (an α-tocopherol oil-in-water emulsion-based Adjuvant System) administered 21 d apart was evaluated in Japanese adults [NCT00989612]. Methods One-hundred healthy subjects aged 20-64 y (stratified [1:1] into two age strata 20-40 y and 41-64 y) received 21 d apart, two doses of AS03-adjuvanted 3.75µg haemagglutinin (HA) H1N1 2009 vaccine. Immunogenicity data by haemagglutination inhibition (HI) assay six months after the first vaccine dose (Day 182) and microneutralization assay following each of the two vaccine doses (Days 21 and 42) and at Day 182 are reported here. Results Persistence of strong HI immune response was observed at Day 182 that met the US and European regulatory thresholds for pandemic influenza vaccines (seroprotection rate: 95%; seroconversion rate: 93%; geometric mean fold-rise: 20). The neutralizing antibody response against the A/Netherlands/602/2009 strain (antigenically similar to vaccine-strain) persisted for at least up to Day 182 (vaccine response rate: 76%; geometric mean titer: 114.4) and paralleled the HI immune response at all time points. No marked difference was observed in HI antibody persistence and neutralising antibody response between the two age strata. The vaccine had a clinically-acceptable safety profile. Conclusion Two priming doses of H1N1 2009 pandemic influenza vaccine induced an immune response persisting for at least six months after the first vaccine dose. This could be beneficial in evaluating the importance and effect of vaccination with this AS03-adjuvanted pandemic influenza vaccine.

  14. Using surveillance data to estimate pandemic vaccine effectiveness against laboratory confirmed influenza A(H1N1)2009 infection: two case-control studies, Spain, season 2009-2010

    PubMed Central

    2011-01-01

    Background Physicians of the Spanish Influenza Sentinel Surveillance System report and systematically swab patients attended to their practices for influenza-like illness (ILI). Within the surveillance system, some Spanish regions also participated in an observational study aiming at estimating influenza vaccine effectiveness (cycEVA study). During the season 2009-2010, we estimated pandemic influenza vaccine effectiveness using both the influenza surveillance data and the cycEVA study. Methods We conducted two case-control studies using the test-negative design, between weeks 48/2009 and 8/2010 of the pandemic season. The surveillance-based study included all swabbed patients in the sentinel surveillance system. The cycEVA study included swabbed patients from seven Spanish regions. Cases were laboratory-confirmed pandemic influenza A(H1N1)2009. Controls were ILI patients testing negative for any type of influenza. Variables collected in both studies included demographic data, vaccination status, laboratory results, chronic conditions, and pregnancy. Additionally, cycEVA questionnaire collected data on previous influenza vaccination, smoking, functional status, hospitalisations, visits to the general practitioners, and obesity. We used logistic regression to calculate adjusted odds ratios (OR), computing pandemic influenza vaccine effectiveness as (1-OR)*100. Results We included 331 cases and 995 controls in the surveillance-based study and 85 cases and 351 controls in the cycEVA study. We detected nine (2.7%) and two (2.4%) vaccine failures in the surveillance-based and cycEVA studies, respectively. Adjusting for variables collected in surveillance database and swabbing month, pandemic influenza vaccine effectiveness was 62% (95% confidence interval (CI): -5; 87). The cycEVA vaccine effectiveness was 64% (95%CI: -225; 96) when adjusting for common variables with the surveillance system and 75% (95%CI: -293; 98) adjusting for all variables collected. Conclusion

  15. Impact of anti-rheumatic treatment on immunogenicity of pandemic H1N1 influenza vaccine in patients with arthritis.

    PubMed

    Kapetanovic, Meliha C; Kristensen, Lars-Erik; Saxne, Tore; Aktas, Teodora; Mörner, Andreas; Geborek, Pierre

    2014-01-02

    An adjuvanted pandemic H1N1 influenza (pH1N1) vaccine (Pandemrix) was reported as highly immunogenic resulting in seroconversion in 77 to 94% of adults after administration of a single dose. The aim of the study was to investigate the impact of different anti-rheumatic treatments on antibody response to pH1N1 vaccination in patients with rheumatoid arthritis (RA) and spondylarthropathy (SpA). Patients with arthritis (n = 291; mean age 57 years, 64% women) participated. Hemagglutination inhibition (HI) assay was performed on blood samples drawn before and after a mean (SD) of 8.3 (4) months following vaccination. A positive immune response i.e. seroconversion was defined as negative prevaccination serum and postvaccination HI titer ≥40 or a ≥4-fold increase in HI titer. All patients were divided into predefined groups based on diagnosis (RA or SpA) and ongoing treatment: methotrexate (MTX), anti-tumor necrosis factor (anti-TNF) as monotherapy, MTX combined with anti-TNF, other biologics (abatacept, rituximab, tocilizumab) and non-steroidal anti-inflammatory drugs (NSAIDs)/analgesics. Predictors of positive immune response were studied using logistic regression analysis. The percentage of patients with positive immune response in the different treatment groups was: 1. RA on MTX 42%; 2. RA on anti-TNF monotherapy 53%; 3. RA on anti-TNF + MTX 43%; 4. RA on other biologics (abatacept 20%, rituximab 10% and tocilizumab 50%); 5. SpA on anti-TNF monotherapy 76%; 6. SpA on anti-TNF + MTX 47%; and 7. SpA on NSAIDs/analgesics 59%. RA patients on rituximab had significantly lower (P < 0.001) and SpA on anti-TNF monotherapy significantly better response rates compared to other treatment groups (P 0.001 to 0.033). Higher age (P < 0.001) predicted impaired immune response. Antibody titers 3 to 6 months after vaccination was generally lower compared to those within the first 3 months but no further decrease in titers were observed 6 to 22 months after

  16. Intercontinental circulation of human influenza A(H1N2) reassortant viruses during the 2001-2002 influenza season.

    PubMed

    Xu, Xiyan; Smith, Catherine B; Mungall, Bruce A; Lindstrom, Stephen E; Hall, Henrietta E; Subbarao, Kanta; Cox, Nancy J; Klimov, Alexander

    2002-11-15

    Reassortant influenza A viruses bearing the H1 subtype of hemagglutinin (HA) and the N2 subtype of neuraminidase (NA) were isolated from humans in the United States, Canada, Singapore, Malaysia, India, Oman, Egypt, and several countries in Europe during the 2001-2002 influenza season. The HAs of these H1N2 viruses were similar to that of the A/New Caledonia/20/99(H1N1) vaccine strain both antigenically and genetically, and the NAs were antigenically and genetically related to those of recent human H3N2 reference strains, such as A/Moscow/10/99(H3N2). All 6 internal genes of the H1N2 reassortants examined originated from an H3N2 virus. This article documents the first widespread circulation of H1N2 reassortants on 4 continents. The current influenza vaccine is expected to provide good protection against H1N2 viruses, because it contains the A/New Caledonia/20/99(H1N1) and A/Moscow/10/99(H3N2)-like viruses, which have H1 and N2 antigens that are similar to those of recent H1N2 viruses.

  17. Guillain-Barré syndrome following receipt of influenza A (H1N1) 2009 monovalent vaccine in Korea with an emphasis on Brighton Collaboration case definition.

    PubMed

    Choe, Young June; Cho, Heeyeon; Bae, Geun-Ryang; Lee, Jong-Koo

    2011-03-03

    In 2009-2010 season, with ongoing of influenza A (H1N1), employment of mass vaccination has generated concerns in issue of adverse events following immunization (AEFI). This study investigates the clinical and laboratory data of reported cases of Guillain-Barré syndrome (GBS) and Fisher syndrome (FS) following receipt of influenza A (H1N1) 2009 monovalent vaccine to the National Vaccine Injury Compensation Program (NVICP) in Korea, with all cases reviewed under case definition developed by Brighton Collaboration GBS Working Group. Retrospective review of medical records for all suspected cases of GBS ad FS following receipt of influenza A (H1N1) monovalent vaccine reported to NVICP from December 1, 2009, through April 28, 2010 was conducted. Additional analyses were performed for identification of levels of diagnostic certainty according to Brighton Collaboration case definition. Of 29 reported cases, 22 were confirmed to meet Brighton criteria level 1, 2, or 3 for GBS (21) or FS (1). Of those, 2 (9.1%) met level 1, 9 (40.9%) met level 2, and 11 (50.0%) met level 3. The male to female ratio was 2:0 in cases with level 1, 8:1 in cases with level 2, and 3:8 in cases with level 3. The mean age was older in cases with level 1 (54.0 ± 26.9) than that of cases with level 2 (25.6 ± 22.8), and level 3 (13.6 ± 2.4, P=0.005). The median onset interval was longer in cases with level 1 (16 days) than that of cases that met level 2 (12.44 days), and 3 (1.09 days, P=0.019). The Brighton case definition was used to improve the quality of AEFI data in Korea, and was applicable in retrospective review of medical records in cases with GBS and FS after influenza A (H1N1) vaccination. These findings suggest that standardized case definition was feasible in clarifying the AEFI data, and to further increase the understanding of possible relationship of influenza vaccine and GBS. Copyright © 2011 Elsevier Ltd. All rights reserved.

  18. Immunogenicity of influenza A(H1N1)pdm09 vaccine in patients with diabetes mellitus: with special reference to age, body mass index, and HbA1c.

    PubMed

    Egawa, Yumi; Ohfuji, Satoko; Fukushima, Wakaba; Yamazaki, Yuko; Morioka, Tomoaki; Emoto, Masanori; Maeda, Kazuhiro; Inaba, Masaaki; Hirota, Yoshio

    2014-01-01

    Subjects with diabetes mellitus are considered to be at high risk of influenza infection and influenza-associated complications. To evaluate the immunogenicity of the influenza A(H1N1)pdm09 vaccine among these subjects, we performed a prospective cohort study and measured hemagglutination inhibition antibody titers at baseline and 3 weeks after vaccination in 49 patients. No serious adverse events were reported. We were able to perform analyses for 48 patients, after excluding one patient with suspected infection. The vaccine induced a rise of about 9-fold in the mean antibody level. The sero-response proportion was 79%, and the sero-protection proportion was 73%. Patients with older age and lower body mass index tended to show lower immune response. Multivariate analysis indicated an independent negative effect of hemoglobin A1c level on the sero-protection proportion. A single A(H1N1)pdm09 vaccination achieved a sufficient level of immunity among diabetic patients, but both clinicians and patients should be aware of the potential for reductions in immune response.

  19. Vaccine Efficacy of Inactivated, Chimeric Hemagglutinin H9/H5N2 Avian Influenza Virus and Its Suitability for the Marker Vaccine Strategy

    PubMed Central

    Kim, Se Mi; Kim, Young-Il; Park, Su-Jin; Kim, Eun-Ha; Kwon, Hyeok-il; Si, Young-Jae; Lee, In-Won; Song, Min-Suk

    2017-01-01

    ABSTRACT In order to produce a dually effective vaccine against H9 and H5 avian influenza viruses that aligns with the DIVA (differentiating infected from vaccinated animals) strategy, we generated a chimeric H9/H5N2 recombinant vaccine that expressed the whole HA1 region of A/CK/Korea/04163/04 (H9N2) and the HA2 region of recent highly pathogenic avian influenza (HPAI) A/MD/Korea/W452/14 (H5N8) viruses. The chimeric H9/H5N2 virus showed in vitro and in vivo growth properties and virulence that were similar to those of the low-pathogenic avian influenza (LPAI) H9 virus. An inactivated vaccine based on this chimeric virus induced serum neutralizing (SN) antibodies against both H9 and H5 viruses but induced cross-reactive hemagglutination inhibition (HI) antibody only against H9 viruses. Thus, this suggests its compatibility for use in the DIVA strategy against H5 strains. Furthermore, the chimeric H9/H5N2 recombinant vaccine protected immunized chickens against lethal challenge by HPAI H5N8 viruses and significantly attenuated virus shedding after infection by both H9N2 and HPAI H5N8 viruses. In mice, serological analyses confirmed that HA1- and HA2 stalk-specific antibody responses were induced by vaccination and that the DIVA principle could be employed through the use of an HI assay against H5 viruses. Furthermore, each HA1- and HA2 stalk-specific antibody response was sufficient to inhibit viral replication and protect the chimeric virus-immunized mice from lethal challenge with both mouse-adapted H9N2 and wild-type HPAI H5N1 viruses, although differences in vaccine efficacy against a homologous H9 virus (HA1 head domain immune-mediated protection) and a heterosubtypic H5 virus (HA2 stalk domain immune-mediated protection) were observed. Taken together, these results demonstrate that the novel chimeric H9/H5N2 recombinant virus is a low-pathogenic virus, and this chimeric vaccine is suitable for a DIVA vaccine with broad-spectrum neutralizing antibody against H5

  20. Non-neutralizing antibodies induced by seasonal influenza vaccine prevent, not exacerbate A(H1N1)pdm09 disease

    PubMed Central

    Kim, Jin Hyang; Reber, Adrian J.; Kumar, Amrita; Ramos, Patricia; Sica, Gabriel; Music, Nedzad; Guo, Zhu; Mishina, Margarita; Stevens, James; York, Ian A.; Jacob, Joshy; Sambhara, Suryaprakash

    2016-01-01

    The association of seasonal trivalent influenza vaccine (TIV) with increased infection by 2009 pandemic H1N1 (A(H1N1)pdm09) virus, initially observed in Canada, has elicited numerous investigations on the possibility of vaccine-associated enhanced disease, but the potential mechanisms remain largely unresolved. Here, we investigated if prior immunization with TIV enhanced disease upon A(H1N1)pdm09 infection in mice. We found that A(H1N1)pdm09 infection in TIV-immunized mice did not enhance the disease, as measured by morbidity and mortality. Instead, TIV-immunized mice cleared A(H1N1)pdm09 virus and recovered at an accelerated rate compared to control mice. Prior TIV immunization was associated with potent inflammatory mediators and virus-specific CD8 T cell activation, but efficient immune regulation, partially mediated by IL-10R-signaling, prevented enhanced disease. Furthermore, in contrast to suggested pathological roles, pre-existing non-neutralizing antibodies (NNAbs) were not associated with enhanced virus replication, but rather with promoted antigen presentation through FcR-bearing cells that led to potent activation of virus-specific CD8 T cells. These findings provide new insights into interactions between pre-existing immunity and pandemic viruses. PMID:27849030

  1. Non-neutralizing antibodies induced by seasonal influenza vaccine prevent, not exacerbate A(H1N1)pdm09 disease.

    PubMed

    Kim, Jin Hyang; Reber, Adrian J; Kumar, Amrita; Ramos, Patricia; Sica, Gabriel; Music, Nedzad; Guo, Zhu; Mishina, Margarita; Stevens, James; York, Ian A; Jacob, Joshy; Sambhara, Suryaprakash

    2016-11-16

    The association of seasonal trivalent influenza vaccine (TIV) with increased infection by 2009 pandemic H1N1 (A(H1N1)pdm09) virus, initially observed in Canada, has elicited numerous investigations on the possibility of vaccine-associated enhanced disease, but the potential mechanisms remain largely unresolved. Here, we investigated if prior immunization with TIV enhanced disease upon A(H1N1)pdm09 infection in mice. We found that A(H1N1)pdm09 infection in TIV-immunized mice did not enhance the disease, as measured by morbidity and mortality. Instead, TIV-immunized mice cleared A(H1N1)pdm09 virus and recovered at an accelerated rate compared to control mice. Prior TIV immunization was associated with potent inflammatory mediators and virus-specific CD8 T cell activation, but efficient immune regulation, partially mediated by IL-10R-signaling, prevented enhanced disease. Furthermore, in contrast to suggested pathological roles, pre-existing non-neutralizing antibodies (NNAbs) were not associated with enhanced virus replication, but rather with promoted antigen presentation through FcR-bearing cells that led to potent activation of virus-specific CD8 T cells. These findings provide new insights into interactions between pre-existing immunity and pandemic viruses.

  2. Pandemic influenza A 2009 (H1N1) vaccination in high risk children with chronic renal diseases: acceptance and perceptions.

    PubMed

    Printza, Nikoleta; Farmaki, Evagelia; Bosdou, Julia; Gkogka, Chrysa; Papachristou, Fotios

    2010-10-01

    We aimed to evaluate the acceptance of pandemic influenza A 2009 vaccination in our high risk children with chronic renal diseases. A total of 64 children/parents of pediatric nephrology department were approached to fill in a standardised questionnaire on influenza immunization profile. The H1N1 vaccination rates were 57.1% for transplant recipients, 61.5% for patients on peritoneal dialysis (PD), 36.4% for patients with various stages of chronic renal disease (CRD) and 26.7% for patients with glomerulonephritis (GN) on immunosuppressive therapy. Children on renal transplantation or PD had a fourfold higher rate of being vaccinated than children with GN (p=0.04). Causes of denying vaccination included fear of adverse effects (48.9%), lack of sufficient data on the new vaccine (31.9%) and others (19.2%). Patients being vaccinated were all urged by their pediatric nephrologist (100%), while patients not vaccinated were negatively influenced by media (41.4%), friends (24.1%), pediatrician (20.7%) and others (13.8%). Regarding parents education, higher level was associated with increased rate of children vaccination (p=0.04). It seems that patients with severe renal disease had better compliance with vaccination. The pediatric nephrologists had the most significant positive influence in contrast to the media which had the most negative influence.

  3. Cell-Based Systems Biology Analysis of Human AS03-Adjuvanted H5N1 Avian Influenza Vaccine Responses: A Phase I Randomized Controlled Trial

    PubMed Central

    Samir, Parimal; Galassie, Allison; Allos, Tara M.; Niu, Xinnan; Gordy, Laura E.; Creech, C. Buddy; Prasad, Nripesh; Jensen, Travis L.; Hill, Heather; Levy, Shawn E.; Joyce, Sebastian; Link, Andrew J.; Edwards, Kathryn M.

    2017-01-01

    Background Vaccine development for influenza A/H5N1 is an important public health priority, but H5N1 vaccines are less immunogenic than seasonal influenza vaccines. Adjuvant System 03 (AS03) markedly enhances immune responses to H5N1 vaccine antigens, but the underlying molecular mechanisms are incompletely understood. Objective and Methods We compared the safety (primary endpoint), immunogenicity (secondary), gene expression (tertiary) and cytokine responses (exploratory) between AS03-adjuvanted and unadjuvanted inactivated split-virus H5N1 influenza vaccines. In a double-blinded clinical trial, we randomized twenty adults aged 18–49 to receive two doses of either AS03-adjuvanted (n = 10) or unadjuvanted (n = 10) H5N1 vaccine 28 days apart. We used a systems biology approach to characterize and correlate changes in serum cytokines, antibody titers, and gene expression levels in six immune cell types at 1, 3, 7, and 28 days after the first vaccination. Results Both vaccines were well-tolerated. Nine of 10 subjects in the adjuvanted group and 0/10 in the unadjuvanted group exhibited seroprotection (hemagglutination inhibition antibody titer > 1:40) at day 56. Within 24 hours of AS03-adjuvanted vaccination, increased serum levels of IL-6 and IP-10 were noted. Interferon signaling and antigen processing and presentation-related gene responses were induced in dendritic cells, monocytes, and neutrophils. Upregulation of MHC class II antigen presentation-related genes was seen in neutrophils. Three days after AS03-adjuvanted vaccine, upregulation of genes involved in cell cycle and division was detected in NK cells and correlated with serum levels of IP-10. Early upregulation of interferon signaling-related genes was also found to predict seroprotection 56 days after first vaccination. Conclusions Using this cell-based systems approach, novel mechanisms of action for AS03-adjuvanted pandemic influenza vaccination were observed. Trial Registration ClinicalTrials.gov NCT

  4. Effect of Priming with H1N1 Influenza Viruses of Variable Antigenic Distances on Challenge with 2009 Pandemic H1N1 Virus

    PubMed Central

    O'Donnell, Christopher D.; Wright, Amber; Vogel, Leatrice N.; Wei, Chih-Jen; Nabel, Gary J.

    2012-01-01

    Compared to seasonal influenza viruses, the 2009 pandemic H1N1 (pH1N1) virus caused greater morbidity and mortality in children and young adults. People over 60 years of age showed a higher prevalence of cross-reactive pH1N1 antibodies, suggesting that they were previously exposed to an influenza virus or vaccine that was antigenically related to the pH1N1 virus. To define the basis for this cross-reactivity, ferrets were infected with H1N1 viruses of variable antigenic distance that circulated during different decades from the 1930s (Alaska/35), 1940s (Fort Monmouth/47), 1950s (Fort Warren/50), and 1990s (New Caledonia/99) and challenged with 2009 pH1N1 virus 6 weeks later. Ferrets primed with the homologous CA/09 or New Jersey/76 (NJ/76) virus served as a positive control, while the negative control was an influenza B virus that should not cross-protect against influenza A virus infection. Significant protection against challenge virus replication in the respiratory tract was observed in ferrets primed with AK/35, FM/47, and NJ/76; FW/50-primed ferrets showed reduced protection, and NC/99-primed ferrets were not protected. The hemagglutinins (HAs) of AK/35, FM/47, and FW/50 differ in the presence of glycosylation sites. We found that the loss of protective efficacy observed with FW/50 was associated with the presence of a specific glycosylation site. Our results suggest that changes in the HA occurred between 1947 and 1950, such that prior infection could no longer protect against 2009 pH1N1 infection. This provides a mechanistic understanding of the nature of serological cross-protection observed in people over 60 years of age during the 2009 H1N1 pandemic. PMID:22674976

  5. Effect of priming with H1N1 influenza viruses of variable antigenic distances on challenge with 2009 pandemic H1N1 virus.

    PubMed

    O'Donnell, Christopher D; Wright, Amber; Vogel, Leatrice N; Wei, Chih-Jen; Nabel, Gary J; Subbarao, Kanta

    2012-08-01

    Compared to seasonal influenza viruses, the 2009 pandemic H1N1 (pH1N1) virus caused greater morbidity and mortality in children and young adults. People over 60 years of age showed a higher prevalence of cross-reactive pH1N1 antibodies, suggesting that they were previously exposed to an influenza virus or vaccine that was antigenically related to the pH1N1 virus. To define the basis for this cross-reactivity, ferrets were infected with H1N1 viruses of variable antigenic distance that circulated during different decades from the 1930s (Alaska/35), 1940s (Fort Monmouth/47), 1950s (Fort Warren/50), and 1990s (New Caledonia/99) and challenged with 2009 pH1N1 virus 6 weeks later. Ferrets primed with the homologous CA/09 or New Jersey/76 (NJ/76) virus served as a positive control, while the negative control was an influenza B virus that should not cross-protect against influenza A virus infection. Significant protection against challenge virus replication in the respiratory tract was observed in ferrets primed with AK/35, FM/47, and NJ/76; FW/50-primed ferrets showed reduced protection, and NC/99-primed ferrets were not protected. The hemagglutinins (HAs) of AK/35, FM/47, and FW/50 differ in the presence of glycosylation sites. We found that the loss of protective efficacy observed with FW/50 was associated with the presence of a specific glycosylation site. Our results suggest that changes in the HA occurred between 1947 and 1950, such that prior infection could no longer protect against 2009 pH1N1 infection. This provides a mechanistic understanding of the nature of serological cross-protection observed in people over 60 years of age during the 2009 H1N1 pandemic.

  6. Heterologous post-infection immunity against Egyptian avian influenza virus (AIV) H9N2 modulates the course of subsequent infection by highly pathogenic AIV H5N1, but vaccination immunity does not.

    PubMed

    Naguib, Mahmoud M; Grund, Christian; Arafa, Abdel-Satar; Abdelwhab, E M; Beer, Martin; Harder, Timm C

    2017-06-01

    In Egypt, zoonotic A/goose/Guangdong/1/96 (gs/GD-like) highly pathogenic avian influenza virus (HPAIV) H5N1 of clade 2.2.1.2 is entrenched in poultry populations and has co-circulated with low-pathogenic avian influenza virus H9N2 of the G1 lineage since 2010. Here, the impact of H9N2 infection or vaccination on the course of consecutive infection with a lethal Egyptian HPAIV H5N1 is studied. Three-week-old chickens were infected with H9N2 or vaccinated with inactivated H9N2 or H5N1 antigens and challenged three weeks later by an HPAIV H5N1. Interestingly, pre-infection of chickens with H9N2 decreased the oral excretion of H5N1 to levels that were comparable to those of H5N1-immunized chickens, but vaccination with inactivated H9N2 did not. H9N2 pre-infection modulated but did not conceal clinical disease by HPAIV H5N1. By contrast, homologous H5 vaccination abolished clinical syndromic surveillance, although vaccinated clinical healthy birds were capable of spreading the virus.

  7. Construction and comparison of different source neuraminidase candidate vaccine strains for human infection with Eurasian avian-like influenza H1N1 virus.

    PubMed

    Liu, Liqi; Lu, Jian; Zhou, Jianfang; Li, Zi; Zhang, Heng; Wang, Dayan; Shu, Yuelong

    2017-12-01

    Human infections with Eurasian avian-like swine influenza H1N1 viruses have been reported in China in past years. One case resulted in death and others were mild case. In 2016, the World Health Organization recommended the use of A/Hunan/42443/2015(H1N1) virus to construct the first candidate vaccine strain for Eurasian avian-like swine influenza H1N1 viruses. Previous reports showed that the neuraminidase of A/Puerto Rico/8/34(H1N1) might improve the viral yield of reassortant viruses. Therefore, we constructed two reassortant candidate vaccine viruses of A/Hunan/42443/2015(H1N1) by reverse genetic technology, with (6+2) and (7+1) gene constitution, respectively. The (6+2) virus had hemagglutinin and neuraminidase from A/Hunan/42443/2015, and the (7+1) one had hemagglutinin from A/Hunan/42443/2015, while all the other genes were from A/Puerto Rico/8/34. Our data revealed that although the neuraminidase of the (7+1) virus was from high yield A/Puerto Rico/8/34, the hemagglutination titer and the hemagglutinin protein content of the (7+1) virus was not higher than that of the (6+2) virus. Both of the (7+1) and (6+2) viruses reached a similar level to that of A/Puerto Rico/8/34 at the usual harvest time in vitro. Therefore, both reassortant viruses are potential candidate vaccine viruses, which could contribute to pandemic preparedness. Copyright © 2017. Published by Elsevier Masson SAS.

  8. Assessment of squalene adjuvanted and non-adjuvanted vaccines against pandemic H1N1 influenza in children 6 months to 17 years of age

    PubMed Central

    Vesikari, Timo; Pepin, Stéphanie; Kusters, Inca; Hoffenbach, Agnès; Denis, Martine

    2012-01-01

    Vaccines were urgently needed in 2009 against A/H1N1 pandemic influenza. Based on the H5N1 experience, it was originally thought that 2 doses of an adjuvanted vaccine were needed for adequate immunogenicity. We tested H1N1 vaccines with or without AF03, a squalene-based adjuvant, in children. Two randomized, open-label, trials were conducted. Participants 3–17 y received two injections of 3.8 µg or 7.5 µg hemagglutinin (HA) with adjuvant or 15 µg HA without adjuvant. Participants aged 6–35 mo received two injections of 1.9 µg or 3.8 µg HA with full or half dose adjuvant or 7.5 µg HA without adjuvant. All subjects 3 to 17 y reached seroprotection (hemagglutination inhibition (HI) titer ≥ 40) after the first dose of the adjuvanted vaccine, and 94% and 98% in the 3–8 and 9–17 y groups respectively with the non-adjuvanted vaccine. In children aged 6–35 mo responses were modest after one dose, but after two doses virtually all children were seroprotected regardless of HA or adjuvant dose. In this age group, antibody titers were 5 to 7 times higher after adjuvanted than non-adjuvanted vaccine. The higher responses with the adjuvanted vaccine were also reflected as better antibody persistence. There was no clustering of adverse events that would be suggestive of a safety signal. While a single injection was sufficient in subjects from 3 y, in children aged 6–35 mo two injections of this A/H1N1 pandemic influenza vaccine were required. Formulation of this vaccine with adjuvant provided a significant advantage for immunogenicity in the latter age group. PMID:22906943

  9. Potency of an inactivated influenza vaccine prepared from A/duck/Hokkaido/162/2013 (H2N1) against a challenge with A/swine/Missouri/2124514/2006 (H2N3) in mice

    PubMed Central

    SUZUKI, Mizuho; OKAMATSU, Masatoshi; HIONO, Takahiro; MATSUNO, Keita; SAKODA, Yoshihiro

    2017-01-01

    H2N2 influenza virus caused a pandemic starting in 1957 but has not been detected in humans since 1968. Thus, most people are immunologically naive to viruses of the H2 subtype. In contrast, H2 influenza viruses are continually isolated from wild birds, and H2N3 viruses were isolated from pigs in 2006. H2 influenza viruses could cause a pandemic if re-introduced into humans. In the present study, a vaccine against H2 influenza was prepared as an effective control measure against a future human pandemic. A/duck/Hokkaido/162/2013 (H2N1), which showed broad antigenic cross-reactivity, was selected from the candidate H2 influenza viruses recently isolated from wild birds in Asian countries. Sufficient neutralizing antibodies against homologous and heterologous viruses were induced in mice after two subcutaneous injections of the inactivated whole virus particle vaccine. The inactivated vaccine induced protective immunity sufficient to reduce the impact of challenges with A/swine/Missouri/2124514/2006 (H2N3). This study demonstrates that the inactivated whole virus particle vaccine prepared from an influenza virus library would be useful against a future H2 influenza pandemic. PMID:28993601

  10. A study of side-effects of Pandemrix® influenza (H1N1) vaccine on board a Norwegian naval vessel.

    PubMed

    Munch, Johan Storm; Johnsen, Bjørn Helge; Birkeland, Ingelin; Finne, Morten; Utkilen, Torun; Bøe, Tommy; Mjølhus, Gry; Sommerfelt-Pettersen, Jan

    2010-01-01

    The frigate His Norwegian Majesty's ship (HNoMS) Fridtjof Nansen was participating in operations in the Gulf of Aden in support of the EU mission tasked with protecting vessels from the threat of piracy. The crew was therefore prioritized and given the first batch of Influenza A (H1N1) vaccine (Pandemrix(®)). To investigate the type, frequency, and intensity of side effects after whole-crew vaccination with Pandemrix vaccine in healthy subjects in a controlled environment. A hundred and thirty-three members of the crew were vaccinated, and then they participated in the study. The side effects of the vaccination were evaluated through a survey. Seventy-five per cent of the vaccinated sailors reported adverse reactions to the vaccine, with 9% not being able to perform their daily duties for one day. Muscle pain, headaches, malaise, and fatigue were the most frequent symptoms reported. The vaccination program using Pandemrix H1N1 vaccine resulted in a high rate of side effects, which were generally mild and resolved within a few days. No serious lasting side effects of the vaccination were reported or registered. The adverse effects of the vaccination did not affect the operational capacity of the vessel.

  11. Conjugating influenza a (H1N1) antigen to n-trimethylaminoethylmethacrylate chitosan nanoparticles improves the immunogenicity of the antigen after nasal administration.

    PubMed

    Liu, Qingfeng; Zheng, Xiaoyao; Zhang, Chi; Shao, Xiayan; Zhang, Xi; Zhang, Qizhi; Jiang, Xinguo

    2015-11-01

    As one of the most serious infectious respiratory diseases, influenza A (H1N1) is a great threat to human health, and it has created an urgent demand for effective vaccines. Nasal immunization can induce both systemic and mucosal immune responses against viruses, and it can serve as an ideal route for vaccination. However, the low immunogenicity of antigens on nasal mucosa is a high barrier for the development of nasal vaccines. In this study, we covalently conjugated an influenza A (H1N1) antigen to the surface of N-trimethylaminoethylmethacrylate chitosan (TMC) nanoparticles (H1N1-TMC/NP) through thioester bonds to increase the immunogenicity of the antigen after nasal administration. SDS-PAGE revealed that most of the antigen was conjugated on TMC nanoparticles, and an in vitro biological activity assay confirmed the stability of the antigen after conjugation. After three nasal immunizations, the H1N1-TMC/NP induced significantly higher levels of serum IgG and mucosal sIgA compared with free antigen. A hemagglutination inhibition assay showed that H1N1-TMC/NP induced much more protective antibodies than antigen-encapsulated nanoparticles or alum-precipitated antigen (I.M.). In the mechanistic study, H1N1-TMC/NP was shown to stimulate macrophages to produce IL-1β and IL-6 and to stimulate spleen lymphocytes to produce IL-2 and IFN-γ. These results indicated that H1N1-TMC/NP may be an effective vaccine against influenza A (H1N1) viruses for use in nasal immunization. © 2015 Wiley Periodicals, Inc.

  12. [Swine-origin influenza H1N1/California--passions and facts].

    PubMed

    Gendon, Iu Z

    2010-01-01

    Analysis of pandemic caused by swine influenza virus H1N1/California showed moderate virulence of this virus compared to pandemic viruses, which caused pandemics in 1918, 1957, and 1968. During seasonal influenza epidemic in countries of southern hemisphere (June-August 2009) despite on circulation of H1N1/California strain, epidemics was caused by human influenza viruses H3N2 and H1N1. It was concluded that strain H1N1/California could not be attributed to pandemic strains of influenza viruses.

  13. Vitamin D, leptin and impact on immune response to seasonal influenza A/H1N1 vaccine in older persons

    PubMed Central

    Sadarangani, Sapna P.; Ovsyannikova, Inna G.; Goergen, Krista; Grill, Diane E.; Poland, Gregory A.

    2016-01-01

    ABSTRACT Background: Influenza-related complications are highest in the elderly. Vaccine efficacy is lower due to immunosenescence. Vitamin D's immunomodulatory role was studied in the context of vaccine response. Methods: We evaluated the effect of baseline 25-(OH) D on vaccine-induced immunological response in a cohort of 159 healthy subjects ages 50–74 in Rochester, MN, who received one dose of seasonal trivalent 2010–2011 influenza vaccine, containing A/California/H1N1- like virus. We examined correlations between 25-(OH) D, leptin, and leptin-related gene SNPs to understand the role of leptin and vitamin D's effects. Results: The median (IQR) baseline for total 25-(OH) D was 44.4 ng/mL (36.6–52.2 ng/mL). No correlation was observed with age. No correlation between 25-(OH) D levels and humoral immune outcomes existed at any timepoint. There was a weak positive correlation between 25-(OH) D levels and change (Day 75-Day 0) in influenza-specific granzyme-B response (r=0.16, p=0.04). We found significant associations between 3 SNPs in the PPARG gene and 25-(OH) D levels (rs1151996, p=0.01; rs1175540, p= 0.02; rs1175544, p=0.03). Conclusion: Several SNPs in the PPARG gene were significantly associated with baseline 25-(OH) D levels. Understanding the functional and mechanistic relationships between vitamin D and influenza vaccine-induced immunity could assist in directing new influenza vaccine design. PMID:26575832

  14. Characteristics of atopic children with pandemic H1N1 influenza viral infection: pandemic H1N1 influenza reveals 'occult' asthma of childhood.

    PubMed

    Hasegawa, Shunji; Hirano, Reiji; Hashimoto, Kunio; Haneda, Yasuhiro; Shirabe, Komei; Ichiyama, Takashi

    2011-02-01

    The number of human cases of pandemic H1N1 influenza viral infection has increased in Japan since April 2009, as it has worldwide. This virus is widespread in the Yamaguchi prefecture in western Japan, where most infected children exhibited respiratory symptoms. Bronchial asthma is thought to be one of the risk factors that exacerbate respiratory symptoms of pandemic H1N1-infected patients, but the pathogenesis remains unclear. We retrospectively investigated the records of 33 children with pandemic H1N1 influenza viral infection who were admitted to our hospital between October and December 2009 and analyzed their clinical features. The percentage of children with asthma attack, with or without abnormal findings on chest radiographs (pneumonia, atelectasis, etc.), caused by pandemic H1N1 influenza infection was significantly higher than that of children with asthma attack and 2008-2009 seasonal influenza infection. Of the 33 children in our study, 22 (66.7%) experienced an asthma attack. Among these children, 20 (90.9%) did not receive long-term management for bronchial asthma, whereas 7 (31.8%) were not diagnosed with bronchial asthma and had experienced their first asthma attack. However, the severity of the attack did not correlate with the severity of the pulmonary complications of pandemic H1N1 influenza viral infection. The pandemic H1N1 influenza virus greatly increases the risk of lower respiratory tract complications such as asthma attack, pneumonia, and atelectasis, when compared to the seasonal influenza virus. Furthermore, our results suggest that pandemic H1N1 influenza viral infection can easily induce a severe asthma attack, pneumonia, and atelectasis in atopic children without any history of either an asthma attack or asthma treatment. © 2011 John Wiley & Sons A/S.

  15. Population‐based surveillance for 2009 pandemic influenza A (H1N1) virus in Guatemala, 2009

    PubMed Central

    Reyes, Lissette; Arvelo, Wences; Estevez, Alejandra; Gray, Jennifer; Moir, Juan C.; Gordillo, Betty; Frenkel, Gal; Ardón, Francisco; Moscoso, Fabiola; Olsen, Sonja J.; Fry, Alicia M.; Lindstrom, Steve; Lindblade, Kim A.

    2010-01-01

    Please cite this paper as: Reyes et al. (2010) Population‐based surveillance for 2009 pandemic influenza A (H1N1) virus in Guatemala, 2009. Influenza and Other Respiratory Viruses 4(3), 129–140. Background  In April 2009, 2009 pandemic influenza A H1N1 (2009 H1N1) was first identified in Mexico but did not cause widespread transmission in neighboring Guatemala until several weeks later. Methodology and principle findings  Using a population‐based surveillance system for hospitalized pneumonia and influenza‐like illness ongoing before the 2009 H1N1 pandemic began, we tracked the onset of 2009 H1N1 infection in Guatemala. We identified 239 individuals infected with influenza A (2009 H1N1) between May and December 2009, of whom 76 were hospitalized with pneumonia and 11 died (case fatality proportion: 4·6%, 95% confidence interval [CI] 2·3–8·1%). The median age of patients infected with 2009 H1N1 was 8·8 years, the median age of those hospitalized with pneumonia was 4·2 years, and five (45·5%) deaths occurred in children <5 years old. Crude rates of hospitalization between May and December 2009 were highest for children <5 years old. Twenty‐one (27·6%) of the patients hospitalized with 2009 H1N1 were admitted to the intensive care unit and eight (10·5%) required mechanical ventilation. Underlying chronic conditions were noted in 14 (18·4%) of patients with pneumonia hospitalized with 2009 H1N1 infection. Conclusions and significance  Chronic illnesses may be underdiagnosed in Guatemala, making it difficult to identify this risk group for vaccination. Children 6 months to 5 years old should be among priority groups for vaccination to prevent serious consequences because of 2009 H1N1 infection. PMID:20409209

  16. Outbreak of pandemic influenza A/H1N1 2009 in Nepal.

    PubMed

    Adhikari, Bal Ram; Shakya, Geeta; Upadhyay, Bishnu Prasad; Prakash Kc, Khagendra; Shrestha, Sirjana Devi; Dhungana, Guna Raj

    2011-03-23

    The 2009 flu pandemic is a global outbreak of a new strain of H1N1 influenza virus. Pandemic influenza A (H1N1) 2009 has posed a serious public health challenge world-wide. Nepal has started Laboratory diagnosis of Pandemic influenza A/H1N1 from mid June 2009 though active screening of febrile travellers with respiratory symptoms was started from April 27, 2009. Out of 609 collected samples, 302 (49.6%) were Universal Influenza A positive. Among the influenza A positive samples, 172(28.3%) were positive for Pandemic influenza A/H1N1 and 130 (21.3%) were Seasonal influenza A. Most of the pandemic cases (53%) were found among young people with ≤ 20 years. Case Fatality Ratio for Pandemic influenza A/H1N1 in Nepal was 1.74%. Upon Molecular characterization, all the isolated pandemic influenza A/H1N1 2009 virus found in Nepal were antigenically and genetically related to the novel influenza A/CALIFORNIA/07/2009-LIKE (H1N1)v type. The Pandemic 2009 influenza virus found in Nepal were antigenically and genetically related to the novel A/CALIFORNIA/07/2009-LIKE (H1N1)v type.

  17. Illness representation on H1N1 influenza and preventive behaviors in the Hong Kong general population.

    PubMed

    Mo, Phoenix K H; Lau, Joseph T F

    2015-12-01

    This study examined illness representations of new influenza Human Swine Influenza A (H1N1) and association with H1N1 preventive behaviors among 300 Chinese adults using a population-based randomized telephone survey. Results showed that relatively few participants thought H1N1 would have serious consequences (12%-15.7%) and few showed negative emotional responses toward H1N1 (9%-24.7%). The majority of the participants thought H1N1 could be controlled by treatment (70.4%-72.7%). Multiple logistic regression analyses showed that treatment control (odds ratio = 1.78) and psychological attribution (odds ratio = .75) were associated with intention to take up influenza vaccination. Emotional representations were associated with lower likelihood of wearing face mask (odds ratio = .77) and hand washing (odds ratio = .67). Results confirm that illness representation variables are associated with H1N1 preventive behaviors. © The Author(s) 2014.

  18. Safety and long-term humoral immune response in adults after vaccination with an H1N1 2009 pandemic influenza vaccine with or without AS03 adjuvant.

    PubMed

    Ferguson, Murdo; Risi, George; Davis, Matthew; Sheldon, Eric; Baron, Mira; Li, Ping; Madariaga, Miguel; Fries, Louis; Godeaux, Olivier; Vaughn, David

    2012-03-01

    In this study (NCT00985088) we evaluated different formulations of an H1N1 2009 pandemic influenza vaccine that deliver various viral hemagglutinin (HA) doses with or without AS03 (a tocopherol-based oil-in-water adjuvant system). A total of 1340 healthy subjects aged ≥18 years were randomized to receive 1 or 2 doses of an adjuvanted (3.75-μg HA/AS03(A) or 1.9-μg HA/AS03(B)) or nonadjuvanted vaccine formulation. Safety and immunogenicity (by hemagglutination-inhibition [HI] assay) after each dose and 6 months after dose 1 are reported here. A single dose of AS03(A)-adjuvanted 3.75-μg HA H1N1 2009 induced the strongest immune responses in subjects aged 18-64 years (seroprotection rate [SPR], 97.2%; seroconversion rate [SCR], 90.1%) as well as in subjects aged >64 years (SPR, 91.1%; SCR, 78.2%) 21 days after vaccination. Six months after dose 1, subjects who received 2 doses of either the adjuvanted formulation or 1 dose of the adjuvanted 3.75-μg HA formulation continued to meet all Center for Biologics Evaluation and Research and Committee for Medicinal Products for Human Use criteria. All formulations had clinically acceptable safety profiles. A single dose of the 3.75-μg HA AS03(A)-adjuvanted H1N1 2009 influenza vaccine was highly immunogenic in both age strata (18-64 and >64 years), inducing long-term persistence of the immune response until at least 6 months after dose 1.

  19. Compatibility of ASO3-adjuvanted H1N1pdm09 and seasonal trivalent influenza vaccines in adults: results of a randomized, controlled trial.

    PubMed

    Scheifele, David W; Ward, Brian J; Dionne, Marc; Vanderkooi, Otto G; Loeb, Mark; Coleman, Brenda L; Li, Yan

    2012-07-06

    When Canada chose a novel adjuvanted vaccine to combat the 2009 influenza pandemic, seasonal trivalent inactivated vaccine (TIV) was also available but compatibility of the two had not been assessed. To compare responses after concurrent or sequential administration of these vaccines, adults 20-59 years old were randomly assigned (1:1) to receive ASO3-adjuvanted H1N1pdm09 vaccine (Arepanrix, GSK, Quebec City, Quebec), with TIV (Vaxigrip, Sanofi Pasteur, Toronto) given concurrently or 21 days later. Blood was obtained at baseline and 21 days after each vaccination to measure hemagglutination inhibition (HAI) titers. Adverse effects were assessed using symptom diaries and personal interviews. 282 participants completed the study (concurrent vaccines 145, sequential vaccines 137). HAI titers to H1N1pdm09 were ≥ 40 at baseline in 15-18% of participants and following vaccination in 91-92%. Initially seropositive subjects (titer ≥ 10) had lower H1N1pdm09 geometric mean HAI titers (GMT) after concurrent than separate vaccinations (320.0 vs 476.5, p=0.039) but both exceeded GM responses of initially naïve participants, which were unaffected by concurrent TIV. Responses to TIV were not lower after concurrent than separate vaccination. Adverse event rates were not increased by concurrent vaccinations above those with H1N1pdm09 vaccine alone. This adjuvanted H1N1pdm09 vaccine was immunogenic and compatible with concurrently administered TIV. Copyright © 2012 Elsevier Ltd. All rights reserved.

  20. Immunogenicity and sustainability of the immune response in Brazilian HIV-1-infected individuals vaccinated with inactivated triple influenza vaccine.

    PubMed

    Souza, Thiago Moreno L; Santini-Oliveira, Marilia; Martorelli, Andressa; Luz, Paula M; Vasconcellos, Mauricio T L; Giacoia-Gripp, Carmem B W; Morgado, Mariza; Nunes, Estevão P; Lemos, Alberto S; Ferreira, Ana C G; Moreira, Ronaldo I; Veloso, Valdiléa G; Siqueira, Marilda; Grinsztejn, Beatriz; Camacho, Luiz A B

    2016-03-01

    HIV-infected individuals have a higher risk of serious illnesses following infection by infection with influenza. Although anti-influenza vaccination is recommended, immunosuppression may limit their response to active immunization. We followed-up a cohort of HIV-infected individuals vaccinated against influenza to assess the immunogenicity and sustainability of the immune response to vaccination. Individuals were vaccinated 2011 with inactivated triple influenza vaccine (TIV), and they had received in 2010 the monovalent anti-A(H1N1)pdm09 vaccine. The sustainability of the immune response to A(H1N1)pdm09 at 12 months after monovalent vaccination fell, both in individuals given two single or two double doses. For these individuals, A(H1N1)pdm09 component from TIV acted as a booster, raising around 40% the number of seroprotected individuals. Almost 70% of the HIV-infected individuals were already seroprotected to A/H3N2 at baseline. Again, TIV boosted over 90% the seroprotection to A/H3N2. Anti-A/H3N2 titers dropped by 20% at 6 months after vaccination. Pre-vaccination seroprotection rate to influenza B (victoria lineage) was the lowest among those tested, seroconversion rates were higher after vaccination. Seroconversion/protection after TIV vaccination did not differ significantly across categories of clinical and demographic variables. Anti-influenza responses in Brazilian HIV-infected individuals reflected both the previous history of virus circulation in Brazil and vaccination. © 2015 Wiley Periodicals, Inc.

  1. Complex patterns of human antisera reactivity to novel 2009 H1N1 and historical H1N1 influenza strains.

    PubMed

    Carter, Donald M; Lu, Hai-Rong; Bloom, Chalise E; Crevar, Corey J; Cherry, Joshua L; Lipman, David J; Ross, Ted M

    2012-01-01

    During the 2009 influenza pandemic, individuals over the age of 60 had the lowest incidence of infection with approximately 25% of these people having pre-existing, cross-reactive antibodies to novel 2009 H1N1 influenza isolates. It was proposed that older people had pre-existing antibodies induced by previous 1918-like virus infection(s) that cross-reacted to novel H1N1 strains. Using antisera collected from a cohort of individuals collected before the second wave of novel H1N1 infections, only a minority of individuals with 1918 influenza specific antibodies also demonstrated hemagglutination-inhibition activity against the novel H1N1 influenza. In this study, we examined human antisera collected from individuals that ranged between the ages of 1 month and 90 years to determine the profile of seropositive influenza immunity to viruses representing H1N1 antigenic eras over the past 100 years. Even though HAI titers to novel 2009 H1N1 and the 1918 H1N1 influenza viruses were positively associated, the association was far from perfect, particularly for the older and younger age groups. Therefore, there may be a complex set of immune responses that are retained in people infected with seasonal H1N1 that can contribute to the reduced rates of H1N1 influenza infection in older populations.

  2. Sequential Infection in Ferrets with Antigenically Distinct Seasonal H1N1 Influenza Viruses Boosts Hemagglutinin Stalk-Specific Antibodies

    PubMed Central

    Kirchenbaum, Greg A.; Carter, Donald M.

    2015-01-01

    ABSTRACT Broadly reactive antibodies targeting the conserved hemagglutinin (HA) stalk region are elicited following sequential infection or vaccination with influenza viruses belonging to divergent subtypes and/or expressing antigenically distinct HA globular head domains. Here, we demonstrate, through the use of novel chimeric HA proteins and competitive binding assays, that sequential infection of ferrets with antigenically distinct seasonal H1N1 (sH1N1) influenza virus isolates induced an HA stalk-specific antibody response. Additionally, stalk-specific antibody titers were boosted following sequential infection with antigenically distinct sH1N1 isolates in spite of preexisting, cross-reactive, HA-specific antibody titers. Despite a decline in stalk-specific serum antibody titers, sequential sH1N1 influenza virus-infected ferrets were protected from challenge with a novel H1N1 influenza virus (A/California/07/2009), and these ferrets poorly transmitted the virus to naive contacts. Collectively, these findings indicate that HA stalk-specific antibodies are commonly elicited in ferrets following sequential infection with antigenically distinct sH1N1 influenza virus isolates lacking HA receptor-binding site cross-reactivity and can protect ferrets against a pathogenic novel H1N1 virus. IMPORTANCE The influenza virus hemagglutinin (HA) is a major target of the humoral immune response following infection and/or seasonal vaccination. While antibodies targeting the receptor-binding pocket of HA possess strong neutralization capacities, these antibodies are largely strain specific and do not confer protection against antigenic drift variant or novel HA subtype-expressing viruses. In contrast, antibodies targeting the conserved stalk region of HA exhibit broader reactivity among viruses within and among influenza virus subtypes. Here, we show that sequential infection of ferrets with antigenically distinct seasonal H1N1 influenza viruses boosts the antibody responses

  3. Incidence of narcolepsy before and after MF59-adjuvanted influenza A(H1N1)pdm09 vaccination in South Korean soldiers.

    PubMed

    Kim, Woo Jung; Lee, Sang Don; Lee, Eun; Namkoong, Kee; Choe, Kang-Won; Song, Joon Young; Cheong, Hee Jin; Jeong, Hye Won; Heo, Jung Yeon

    2015-09-11

    Previous reports mostly from Europe suggested an association between an occurrence of narcolepsy and an influenza A(H1N1)pdm09 vaccine adjuvanted with AS03 (Pandemrix(®)). During the 2009 H1N1 pandemic vaccination campaign, the Korean military performed a vaccination campaign with one type of influenza vaccine containing MF59-adjuvants. This study was conducted to investigate the background incidence rate of narcolepsy in South Korean soldiers and the association of the MF59-adjuvanted vaccine with the occurrence of narcolepsy in a young adult group. To assess the incidence of narcolepsy, we retrospectively reviewed medical records of suspicious cases of narcolepsy in 2007-2013 in the whole 20 military hospitals of the Korean military. The screened cases were classified according to the Brighton Collaboration case definition of narcolepsy. After obtaining the number of confirmed cases of narcolepsy per 3 months in 2007-2013, we compared the crude incidence rate of narcolepsy before and after the vaccination campaign. We included 218 narcolepsy suspicious cases in the initial review, which were screened by the diagnostic code on the computerized disease registry in 2007-2013. Forty-one cases were finally diagnosed with narcolepsy in 2007-2013 (male sex, 95%; median age, 21 years). The average background incidence rate of narcolepsy in Korean soldiers was 0.91 cases per 100,000 persons per year. During the 9 months before vaccination implementation (April to December 2009), 6 narcolepsy cases occurred, whereas during the next 9 months (January to September 2010) including the 3-month vaccination campaign, 5 cases occurred. The incidence of narcolepsy in South Korean soldiers was not increased after the pandemic vaccination campaign using the MF59-adjuvanted vaccine. Our results suggest that the MF59-adjuvanted H1N1 vaccine did not contribute to the occurrence of narcolepsy in this young adult group. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Incidence and Epidemiology of Hospitalized Influenza Cases in Rural Thailand during the Influenza A (H1N1)pdm09 Pandemic, 2009–2010

    PubMed Central

    Baggett, Henry C.; Chittaganpitch, Malinee; Thamthitiwat, Somsak; Prapasiri, Prabda; Naorat, Sathapana; Sawatwong, Pongpun; Ditsungnoen, Darunee; Olsen, Sonja J.; Simmerman, James M.; Srisaengchai, Prasong; Chantra, Somrak; Peruski, Leonard F.; Sawanpanyalert, Pathom; Maloney, Susan A.; Akarasewi, Pasakorn

    2012-01-01

    Background Data on the burden of the 2009 influenza pandemic in Asia are limited. Influenza A(H1N1)pdm09 was first reported in Thailand in May 2009. We assessed incidence and epidemiology of influenza-associated hospitalizations during 2009–2010. Methods We conducted active, population-based surveillance for hospitalized cases of acute lower respiratory infection (ALRI) in all 20 hospitals in two rural provinces. ALRI patients were sampled 1∶2 for participation in an etiology study in which nasopharyngeal swabs were collected for influenza virus testing by PCR. Results Of 7,207 patients tested, 902 (12.5%) were influenza-positive, including 190 (7.8%) of 2,436 children aged <5 years; 86% were influenza A virus (46% A(H1N1)pdm09, 30% H3N2, 6.5% H1N1, 3.5% not subtyped) and 13% were influenza B virus. Cases of influenza A(H1N1)pdm09 first peaked in August 2009 when 17% of tested patients were positive. Subsequent peaks during 2009 and 2010 represented a mix of influenza A(H1N1)pdm09, H3N2, and influenza B viruses. The estimated annual incidence of hospitalized influenza cases was 136 per 100,000, highest in ages <5 years (477 per 100,000) and >75 years (407 per 100,000). The incidence of influenza A(H1N1)pdm09 was 62 per 100,000 (214 per 100,000 in children <5 years). Eleven influenza-infected patients required mechanical ventilation, and four patients died, all adults with influenza A(H1N1)pdm09 (1) or H3N2 (3). Conclusions Influenza-associated hospitalization rates in Thailand during 2009–10 were substantial and exceeded rates described in western countries. Influenza A(H1N1)pdm09 predominated, but H3N2 also caused notable morbidity. Expanded influenza vaccination coverage could have considerable public health impact, especially in young children. PMID:23139802

  5. Identification and characterization of a highly pathogenic H5N1 avian influenza A virus during an outbreak in vaccinated chickens in Egypt.

    PubMed

    Amen, O; Vemula, S V; Zhao, J; Ibrahim, R; Hussein, A; Hewlett, I K; Moussa, S; Mittal, S K

    2015-12-02

    Highly pathogenic avian influenza A (HPAI) H5N1 viruses continue to be a major veterinary and public health problem in Egypt. Continued surveillance of these viruses is necessary to devise strategies to control the spread of the virus and to monitor its evolutionary patterns. This is a report of the identification of a variant strain of HPAI H5N1 virus during an outbreak in 2010 in vaccinated chicken flocks in a poultry farm in Assiut, Egypt. Vaccination of chickens with an oil-emulsified inactivated A/chicken/Mexico/232/94 (H5N2) vaccine induced high levels of hemagglutination inhibition (HI) antibody titers reaching up to 9 log2. However, all flocks irrespective of the number of vaccine doses and the resultant HI titer levels came down with severe influenza infections. The qRT-PCR and rapid antigen test confirmed the influenza virus to be from H5N1 subtype. Sequencing of the hemagglutinin (HA) gene fragment from ten independent samples demonstrated that a single H5N1 strain was involved. This strain belonged to clade 2.2.1 and had several mutations in the receptor-binding site of the HA protein, thereby producing a variant strain of HPAI H5N1 virus which was antigenically different from the parent clade 2.2.1 virus circulating in Egypt at that time. In order to define the variability in HPAI H5N1 viruses over time in Egypt, we sequenced another H5N1 virus that was causing infections in chickens in 2014. Phylogenetic analysis revealed that both viruses had further distanced from the parent virus circulating during 2010. This study highlights that the antigenic mutations in HPAI H5N1 viruses represent a definitive challenge for the development of an effective vaccine for poultry. Overall, the results emphasize the need for continued surveillance of H5N1 outbreaks and extensive characterization of virus isolates from vaccinated and non-vaccinated poultry populations to better understand genetic changes and their implications. Copyright © 2015 Elsevier B.V. All

  6. 2009 H1N1 Flu Vaccine Facts

    MedlinePlus

    ... turn Javascript on. Feature: Flu 2009 H1N1 Flu Vaccine Facts Past Issues / Fall 2009 Table of Contents ... H1N1 flu vaccine. 1 The 2009 H1N1 flu vaccine is safe and well tested. Clinical trials conducted ...

  7. High proportions of regulatory B and T cells are associated with decreased cellular responses to pH1N1 influenza vaccine in HIV-infected children and youth (IMPAACT P1088)

    PubMed Central

    Weinberg, Adriana; Muresan, Petronella; Fenton, Terence; Richardson, Kelly; Dominguez, Teresa; Bloom, Anthony; Petzold, Elizabeth; Anthony, Patricia; Cunningham, Coleen K.; Spector, Stephen A.; Nachman, Sharon; Siberry, George K.; Handelsman, Edward; Flynn, Patricia M.

    2013-01-01

    HIV-infected individuals have poor responses to inactivated influenza vaccines. To evaluate the potential role of regulatory T (Treg) and B cells (Breg), we analyzed their correlation with humoral and cell-mediated immune (CMI) responses to pandemic influenza (pH1N1) monovalent vaccine in HIV-infected children and youth. Seventy-four HIV-infected, 4- to 25-y old participants in a 2-dose pH1N1 vaccine study had circulating and pH1N1-stimulated Treg and Breg measured by flow cytometry at baseline, post-dose 1 and post-dose 2. Concomitantly, CMI was measured by ELISPOT and flow cytometry; and antibodies by hemagglutination inhibition (HAI). At baseline, most of the participants had pH1N1-specific IFNγ ELISPOT responses, whose magnitude positively correlated with the baseline pH1N1, but not with seasonal H1N1 HAI titers. pH1N1-specific IFNγ ELISPOT responses did not change post-dose 1 and significantly decreased post-dose 2. In contrast, circulating CD4+CD25+% and CD4+FOXP3+% Treg increased after vaccination. The decrease in IFNγ ELISPOT results was marginally associated with higher pH1N1-specific CD19+FOXP3+ and CD4+TGFβ+% Breg and Treg, respectively. In contrast, increases in HAI titers post-dose 1 were associated with significantly higher circulating CD19+CD25+% post-dose 1, whereas increases in IFNγ ELISPOT results post-dose 1 were associated with higher circulating CD4+/C8+CD25+FOXP3+%. In conclusion, in HIV-infected children and youth, influenza-specific Treg and Breg may contribute to poor responses to vaccination. However, robust humoral and CMI responses to vaccination may result in increased circulating Treg and/or Breg, establishing a feed-back mechanism. PMID:23370281

  8. An effective quarantine measure reduced the total incidence of influenza A H1N1 in the workplace: another way to control the H1N1 flu pandemic.

    PubMed

    Miyaki, Koichi; Sakurazawa, Hirofumi; Mikurube, Hajime; Nishizaka, Mika; Ando, Hidehiko; Song, Yixuan; Shimbo, Takuro

    2011-01-01

    To evaluate the effectiveness of a non-vaccine quarantine measure against pandemic influenza A H1N1 in workplaces. Design was quasi-cluster randomized controlled trial in two sibling companies (Cohort 1 n=6,634, Cohort 2 n=8,500). The follow-up period was from July 1st, 2009 to February 19th, 2010 (233 days). Intervention was voluntary waiting at home on full pay if the family became Influenza like Illness (ILI). The incidences of influenza A H1N1 and those of the subgroups whose families got ILI in both cohorts were compared by a Cox regression model and log-rank test. There were 189 and 270 workers who got H1N1 infection during the follow-up period in each cohort. In this period 317 workers in Cohort 1 were asked to wait at home for several days (100% obeyed). The intervention group (Cohort 1) showed a statistically significant lower risk (p for log-rank test=0.033) compared with the control (Cohort 2), and the hazard ratio of the intervention was 0.799 [0.658-0.970] after adjusting for age, sex, BMI and smoking status. The workers who were asked to wait at home showed H1N1 infection more frequently (49 out of 317) compared with the workers whose family got ILI but were not asked to wait and work regularly (77 out of 990, RR=2.17 [1.48-3.18]). The waiting on full pay policy in the workplace reduced the overall risk of influenza A H1N1 by about 20% in one flu season in Japan. This kind of non-vaccine measure will be a promising option in workplaces to control the next flu pandemic.

  9. Suboptimal protection against H5N1 highly pathogenic avian influenza viruses from Vietnam in ducks vaccinated with commercial poultry vaccines.

    PubMed

    Cha, Ra Mi; Smith, Diane; Shepherd, Eric; Davis, C Todd; Donis, Ruben; Nguyen, Tung; Nguyen, Hoang Dang; Do, Hoa Thi; Inui, Ken; Suarez, David L; Swayne, David E; Pantin-Jackwood, Mary

    2013-10-09

    Domestic ducks are the second most abundant poultry species in many Asian countries including Vietnam, and play a critical role in the epizootiology of H5N1 highly pathogenic avian influenza (HPAI) [FAO]. In this study, we examined the protective efficacy in ducks of two commercial H5N1 vaccines widely used in Vietnam; Re-1 containing A/goose/Guangdong/1/1996 hemagglutinin (HA) clade 0 antigens, and Re-5 containing A/duck/Anhui/1/2006 HA clade 2.3.4 antigens. Ducks received two doses of either vaccine at 7 and at 14 or 21 days of age followed by challenge at 30 days of age with viruses belonging to the HA clades 1.1, 2.3.4.3, 2.3.2.1.A and 2.3.2.1.B isolated between 2008 and 2011 in Vietnam. Ducks vaccinated with the Re-1 vaccine were protected after infection with the two H5N1 HPAI viruses isolated in 2008 (HA clades 1.1 and 2.3.4.3) showing no mortality and limited virus shedding. The Re-1 and Re-5 vaccines conferred 90-100% protection against mortality after challenge with the 2010 H5N1 HPAI viruses (HA clade 2.3.2.1.A); but vaccinated ducks shed virus for more than 7 days after challenge. Similarly, the Re-1 and Re-5 vaccines only showed partial protection against the 2011 H5N1 HPAI viruses (HA clade 2.3.2.1.A and 2.3.2.1.B), with a high proportion of vaccinated ducks shedding virus for more than 10 days. Furthermore, 50% mortality was observed in ducks vaccinated with Re-1 and challenged with the 2.3.2.1.B virus. The HA proteins of the 2011 challenge viruses had the greatest number of amino acid differences from the two vaccines as compared to the viruses from 2008 and 2009, which correlates with the lesser protection observed with these viruses. These studies demonstrate the suboptimal protection conferred by the Re-1 and Re-5 commercial vaccines in ducks against H5N1 HPAI clade 2.3.2.1 viruses, and underscore the importance of monitoring vaccine efficacy in the control of H5N1 HPAI in ducks. Published by Elsevier Ltd.

  10. Events supposedly attributable to vaccination or immunization during pandemic influenza A (H1N1) vaccination campaigns in Latin America and the Caribbean.

    PubMed

    Ropero-Álvarez, A M; Whittembury, A; Bravo-Alcántara, P; Kurtis, H J; Danovaro-Holliday, M C; Velandia-González, M

    2015-01-01

    As part of the vaccination activities against influenza A[H1N1]pdm vaccine in 2009-2010, countries in Latin American and the Caribbean (LAC) implemented surveillance of events supposedly attributable to vaccines and immunization (ESAVI). We describe the serious ESAVI reported in LAC in order to further document the safety profile of this vaccine and highlight lessons learned. We reviewed data from serious H1N1 ESAVI cases from LAC countries reported to the Pan American Health Organization/World Health Organization. We estimated serious ESAVI rates by age and target group, as well as by clinical diagnosis, and completed descriptive analyses of final outcomes and classifications given in country. A total of 1000 serious ESAVI were reported by 18 of the 29 LAC countries that vaccinated against A[H1N1]pdm. The overall reporting rate in LAC was 6.91 serious ESAVI per million doses, with country reporting rates ranging from 0.77 to 64.68 per million doses. Rates were higher among pregnant women (16.25 per million doses) when compared to health care workers (13.54 per million doses) and individuals with chronic disease (4.03 per million doses). The top three most frequent diagnoses were febrile seizures (12.0%), Guillain-Barré Syndrome (10.5%) and acute pneumonia (8.0%). Almost half (49.1%) of the serious ESAVI were reported among children aged <18 years of age; within this group, the highest proportion of cases was reported among those aged <2 years (53.1%). Of all serious ESAVI reported, 37.8% were classified as coincidental, 35.3% as related to vaccine components, 26.4% as non-conclusive and 0.5% as a programmatic error. This regional overview of A[H1N1]pdm vaccine safety data in LAC estimated the rate of serious ESAVI at lower levels than other studies. However, the ESAVI diagnosis distribution is comparable to the published literature. Lessons learned can be applied in the response to future pandemics. Copyright © 2014. Published by Elsevier Ltd.

  11. 2015/16 seasonal vaccine effectiveness against hospitalisation with influenza A(H1N1)pdm09 and B among elderly people in Europe: results from the I-MOVE+ project

    PubMed Central

    Rondy, Marc; Larrauri, Amparo; Casado, Itziar; Alfonsi, Valeria; Pitigoi, Daniela; Launay, Odile; Syrjänen, Ritva K; Gefenaite, Giedre; Machado, Ausenda; Vučina, Vesna Višekruna; Horváth, Judith Krisztina; Paradowska-Stankiewicz, Iwona; Marbus, Sierk D; Gherasim, Alin; Díaz-González, Jorge Alberto; Rizzo, Caterina; Ivanciuc, Alina E; Galtier, Florence; Ikonen, Niina; Mickiene, Aukse; Gomez, Veronica; Kurečić Filipović, Sanja; Ferenczi, Annamária; Korcinska, Monika R; van Gageldonk-Lafeber, Rianne; Valenciano, Marta

    2017-01-01

    We conducted a multicentre test-negative case–control study in 27 hospitals of 11 European countries to measure 2015/16 influenza vaccine effectiveness (IVE) against hospitalised influenza A(H1N1)pdm09 and B among people aged ≥ 65 years. Patients swabbed within 7 days after onset of symptoms compatible with severe acute respiratory infection were included. Information on demographics, vaccination and underlying conditions was collected. Using logistic regression, we measured IVE adjusted for potential confounders. We included 355 influenza A(H1N1)pdm09 cases, 110 influenza B cases, and 1,274 controls. Adjusted IVE against influenza A(H1N1)pdm09 was 42% (95% confidence interval (CI): 22 to 57). It was 59% (95% CI: 23 to 78), 48% (95% CI: 5 to 71), 43% (95% CI: 8 to 65) and 39% (95% CI: 7 to 60) in patients with diabetes mellitus, cancer, lung and heart disease, respectively. Adjusted IVE against influenza B was 52% (95% CI: 24 to 70). It was 62% (95% CI: 5 to 85), 60% (95% CI: 18 to 80) and 36% (95% CI: -23 to 67) in patients with diabetes mellitus, lung and heart disease, respectively. 2015/16 IVE estimates against hospitalised influenza in elderly people was moderate against influenza A(H1N1)pdm09 and B, including among those with diabetes mellitus, cancer, lung or heart diseases. PMID:28797322

  12. Risk of Guillain-Barré syndrome after exposure to pandemic influenza A(H1N1)pdm09 vaccination or infection: a Norwegian population-based cohort study.

    PubMed

    Ghaderi, Sara; Gunnes, Nina; Bakken, Inger Johanne; Magnus, Per; Trogstad, Lill; Håberg, Siri Eldevik

    2016-01-01

    Vaccinations and infections are possible triggers of Guillain-Barré syndrome (GBS). However, studies on GBS after vaccinations during the influenza A(H1N1)pmd09 pandemic in 2009, show inconsistent results. Only few studies have addressed the role of influenza infection. We used information from national health data-bases with information on the total Norwegian population (N = 4,832,211). Cox regression analyses with time-varying covariates and self-controlled case series was applied. The risk of being hospitalized with GBS during the pandemic period, within 42 days after an influenza diagnosis or pandemic vaccination was estimated. There were 490 GBS cases during 2009-2012 of which 410 cases occurred after October 1, 2009 of which 46 new cases occurred during the peak period of the influenza pandemic. An influenza diagnosis was registered for 2.47% of the population and the vaccination coverage was 39.25%. The incidence rate ratio of GBS during the pandemic peak relative to other periods was 1.46 [95% confidence interval (CI) 1.08-1.98]. The adjusted hazard ratio (HR) of GBS within 42 days after a diagnosis of pandemic influenza was 4.89 (95% CI 1.17-20.36). After pandemic vaccination the adjusted HR was 1.11 (95% CI 0.51-2.43). Our results indicated that there was a significantly increased risk of GBS during the pandemic season and after pandemic influenza infection. However, vaccination did not increase the risk of GBS. The small number of GBS cases in this study warrants caution in the interpretation of the findings.

  13. Safety and efficacy of a novel live attenuated influenza vaccine against pandemic H1N1 in swine

    USDA-ARS?s Scientific Manuscript database

    On June 11, 2009 the World Health Organization (WHO) declared that the outbreaks caused by novel swine-origin influenza A (H1N1) virus had reached pandemic proportions. The pandemic H1N1 (H1N1pdm) is the predominant influenza strain in the human population. It has also crossed the species barriers a...

  14. Prime-boost immunization using a DNA vaccine delivered by attenuated Salmonella enterica serovar typhimurium and a killed vaccine completely protects chickens from H5N1 highly pathogenic avian influenza virus.

    PubMed

    Pan, Zhiming; Zhang, Xiaoming; Geng, Shizhong; Fang, Qiang; You, Meng; Zhang, Lei; Jiao, Xinan; Liu, Xiufan

    2010-04-01

    H5N1 highly pathogenic avian influenza virus (HPAIV) has posed a great threat not only for the poultry industry but also for human health. However, an effective vaccine to provide a full spectrum of protection is lacking in the poultry field. In the current study, a novel prime-boost vaccination strategy against H5N1 HPAIV was developed: chickens were first orally immunized with a hemagglutinin (HA) DNA vaccine delivered by attenuated Salmonella enterica serovar Typhimurium, and boosting with a killed vaccine followed. Chickens in the combined vaccination group but not in single vaccination and control groups were completely protected against disease following H5N1 HPAIV intranasal challenge, with no clinical signs and virus shedding. Chickens in the prime-boost group also generated significantly higher serum hemagglutination inhibition (HI) titers and intestinal mucosal IgA titers against avian influenza virus (AIV) and higher host immune cellular responses than those from other groups before challenge. These results demonstrated that the prime-boost vaccination strategy provides an effective way to prevent and control H5N1 highly pathogenic avian influenza virus.

  15. Higher vaccine effectiveness in seasons with predominant circulation of seasonal influenza A(H1N1) than in A(H3N2) seasons: test-negative case-control studies using surveillance data, Spain, 2003-2011.

    PubMed

    Savulescu, Camelia; Jiménez-Jorge, Silvia; Delgado-Sanz, Concha; de Mateo, Salvador; Pozo, Francisco; Casas, Inmaculada; Larrauri, Amparo

    2014-07-31

    We used data provided by the Spanish influenza surveillance system to measure seasonal influenza vaccine effectiveness (VE) against medically attended cases, laboratory confirmed with the predominately circulating influenza virus over eight seasons (2003-2011). Using the test-negative case-control design, we compared the vaccination status of swabbed influenza-like illnesses (ILI) patients who were laboratory confirmed with predominantly circulating influenza strain in the season (cases) to that of ILI patients testing negative for any influenza (controls). Data on age, sex, vaccination status and laboratory results were available for all seasons. We used logistic regression to calculate adjusted influenza VE for age, week of swabbing, Spanish region and season. We calculated the influenza VE by each season and pooling the seasons with the same predominant type/subtype. Overall influenza VE against infection with A(H3N2) subtype (four seasons) was 31 (95% confidence interval (CI):10; 48). For seasonal influenza A(H1N1) (two seasons), the effectiveness was 86% (95% CI: 65; 94). Against B infection (three seasons), influenza VE was 47% (95% CI: 27; 62). The Spanish influenza surveillance system allowed estimating influenza VE in the studied seasons for the predominant strain. Strengthening the influenza surveillance will result in more precise VE estimates for decision making. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. Longitudinal 2 years field study of conventional vaccination against highly pathogenic avian influenza H5N1 in layer hens.

    PubMed

    Rudolf, Miriam; Pöppel, Manfred; Fröhlich, Andreas; Breithaupt, Angele; Teifke, Jens; Blohm, Ulrike; Mettenleiter, Thomas; Beer, Martin; Harder, Timm

    2010-10-04

    A licensed, inactivated vaccine based on a low pathogenic avian influenza virus strain (H5N2) was evaluated in layer hens kept under field conditions during a 2-year period. Vaccine efficacy was investigated by specific antibodies and by challenge-contact experiments using highly pathogenic avian influenza viruses (HPAIV) H5N1. Basic immunization with two applications induced clinical protection. Virus excretion by vaccinated hens was significantly reduced compared to non-vaccinated controls; transmission to non-vaccinated and vaccinated contact birds was not fully interrupted. Vaccination efficacy is influenced by several factors including antigenic relatedness between vaccine and field strains, but also by species, age and type of commercial uses of the host. Limitations and risks of HPAIV vaccination as silent spread of HPAIV and emergence of escape mutants must be considered a priori and appropriate corrective measures have to be installed. Copyright © 2010 Elsevier Ltd. All rights reserved.

  17. Recombinant Parainfluenza Virus 5 Expressing Hemagglutinin of Influenza A Virus H5N1 Protected Mice against Lethal Highly Pathogenic Avian Influenza Virus H5N1 Challenge

    PubMed Central

    Li, Zhuo; Mooney, Alaina J.; Gabbard, Jon D.; Gao, Xiudan; Xu, Pei; Place, Ryan J.; Hogan, Robert J.; Tompkins, S. Mark

    2013-01-01

    A safe and effective vaccine is the best way to prevent large-scale highly pathogenic avian influenza virus (HPAI) H5N1 outbreaks in the human population. The current FDA-approved H5N1 vaccine has serious limitations. A more efficacious H5N1 vaccine is urgently needed. Parainfluenza virus 5 (PIV5), a paramyxovirus, is not known to cause any illness in humans. PIV5 is an attractive vaccine vector. In our studies, a single dose of a live recombinant PIV5 expressing a hemagglutinin (HA) gene of H5N1 (rPIV5-H5) from the H5N1 subtype provided sterilizing immunity against lethal doses of HPAI H5N1 infection in mice. Furthermore, we have examined the effect of insertion of H5N1 HA at different locations within the PIV5 genome on the efficacy of a PIV5-based vaccine. Interestingly, insertion of H5N1 HA between the leader sequence, the de facto promoter of PIV5, and the first viral gene, nucleoprotein (NP), did not lead to a viable virus. Insertion of H5N1 HA between NP and the next gene, V/phosphorprotein (V/P), led to a virus that was defective in growth. We have found that insertion of H5N1 HA at the junction between the small hydrophobic (SH) gene and the hemagglutinin-neuraminidase (HN) gene gave the best immunity against HPAI H5N1 challenge: a dose as low as 1,000 PFU was sufficient to protect against lethal HPAI H5N1 challenge in mice. The work suggests that recombinant PIV5 expressing H5N1 HA has great potential as an HPAI H5N1 vaccine. PMID:23077314

  18. Infants hospitalized in intensive care units with 2009 H1N1 influenza infection, California, 2009-2010.

    PubMed

    Yen, Cynthia J; Louie, Janice K; Schechter, Robert

    2012-03-01

    The 2009 H1N1 influenza virus emerged in April 2009 and primarily affected children and young adults. Few reports describe 2009 H1N1 influenza infection in infants. This report describes the clinical and epidemiologic features of 2009 H1N1 influenza in critically ill infants younger than 1 year of age. Laboratory-confirmed cases were reported to the California Department of Public Health as part of public health surveillance for 2009 H1N1 influenza. Data were collected using standardized report forms and medical-chart abstractions. From April 23, 2009 through May 1, 2010, 82 cases of infants hospitalized in the intensive care unit with 2009 H1N1 influenza were reported in California. Medical charts were available for 77 of the infants, whose median age was 109 days (range: 1-361 days). Twenty-seven (35%) infants had a gestational age of 36 weeks or less. More than half (46; 60%) of the infants had at least 1 reported chronic medical condition. Thirty-five (45%) infants required mechanical ventilation; 7 (9%) died. Five infants were hospitalized since birth and acquired influenza infection during their admission; 2 (40%) of these infants died. Infants who are premature or with chronic conditions seem to be at increased risk for developing severe 2009 H1N1 influenza infection. We encourage clinicians to maintain high suspicion for influenza in infants when influenza viruses are circulating. Vaccination should be encouraged among contacts of infants <6 months of age, who are too young to be immunized or treated with licensed antivirals. Infection control measures should also be implemented in hospital settings to reduce nosocomial transmission.

  19. Antibody Persistence and Booster Responses to Split-Virion H5N1 Avian Influenza Vaccine in Young and Elderly Adults

    PubMed Central

    Lazarus, Rajeka; Kelly, Sarah; Snape, Matthew D.; Vandermeulen, Corinne; Voysey, Merryn; Hoppenbrouwers, Karel; Hens, Annick; Van Damme, Pierre; Pepin, Stephanie; Leroux-Roels, Isabel; Leroux-Roels, Geert; Pollard, Andrew J.

    2016-01-01

    Avian influenza continues to circulate and remains a global health threat not least because of the associated high mortality. In this study antibody persistence, booster vaccine response and cross-clade immune response between two influenza A(H5N1) vaccines were compared. Participants aged over 18-years who had previously been immunized with a clade 1, A/Vietnam vaccine were re-immunized at 6-months with 7.5 μg of the homologous strain or at 22-months with a clade 2, alum-adjuvanted, A/Indonesia vaccine. Blood sampled at 6, 15 and 22-months after the primary course was used to assess antibody persistence. Antibody concentrations 6-months after primary immunisation with either A/Vietnam vaccine 30 μg alum-adjuvanted vaccine or 7.5 μg dose vaccine were lower than 21-days after the primary course and waned further with time. Re-immunization with the clade 2, 30 μg alum-adjuvanted vaccine confirmed cross-clade reactogenicity. Antibody cross-reactivity between A(H5N1) clades suggests that in principle a prime-boost vaccination strategy may provide both early protection at the start of a pandemic and improved antibody responses to specific vaccination once available. Trial Registration: ClinicalTrials.gov NCT00415129 PMID:27814377

  20. [Influenza A/H5N1 virus outbreaks and prepardness to avert flu pandemic].

    PubMed

    Haque, A; Lucas, B; Hober, D

    2007-01-01

    This review emphasizes the need to improve the knowledge of the biology of H5N1 virus, a candidate for causing the next influenza pandemic. In-depth knowledge of mode of infection, mechanisms of pathogenesis and immune response will help in devising an efficient and practical control strategy against this flu virus. We have discussed limitations of currently available vaccines and proposed novel approaches for making better vaccines against H5N1 influenza virus. They include cell-culture system, reverse genetics, adjuvant development. Our review has also underscored the concept of therapeutic vaccine (anti-disease vaccine), which is aimed at diminishing 'cytokine storm' seen in acute respiratory distress syndrome and/or hemophagocytosis.

  1. Attenuation of the influenza virus by microRNA response element in vivo and protective efficacy against 2009 pandemic H1N1 virus in mice.

    PubMed

    Feng, Chunlai; Tan, Mingming; Sun, Wenkui; Shi, Yi; Xing, Zheng

    2015-09-01

    The 2009 influenza pandemics underscored the need for effective vaccines to block the spread of influenza virus infection. Most live attenuated vaccines utilize cold-adapted, temperature-sensitive virus. An alternative to live attenuated virus is presented here, based on microRNA-induced gene silencing. In this study, miR-let-7b target sequences were inserted into the H1N1 genome to engineer a recombinant virus - miRT-H1N1. Female BALB/c mice were vaccinated intranasally with the miRT-H1N1 and challenged with a lethal dose of homologous virus. This miRT-H1N1 virus was attenuated in mice, while it exhibited wild-type characteristics in chicken embryos. Mice vaccinated intranasally with the miRT-H1N1 responded with robust immunity that protected the vaccinated mice from a lethal challenge with the wild-type 2009 pandemic H1N1 virus. These results indicate that the influenza virus containing microRNA response elements (MREs) is attenuated in vivo and can be used to design a live attenuated vaccine. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  2. Extreme Evolutionary Conservation of Functionally Important Regions in H1N1 Influenza Proteome

    PubMed Central

    Warren, Samantha; Wan, Xiu-Feng; Conant, Gavin; Korkin, Dmitry

    2013-01-01

    The H1N1 subtype of influenza A virus has caused two of the four documented pandemics and is responsible for seasonal epidemic outbreaks, presenting a continuous threat to public health. Co-circulating antigenically divergent influenza strains significantly complicates vaccine development and use. Here, by combining evolutionary, structural, functional, and population information about the H1N1 proteome, we seek to answer two questions: (1) do residues on the protein surfaces evolve faster than the protein core residues consistently across all proteins that constitute the influenza proteome? and (2) in spite of the rapid evolution of surface residues in influenza proteins, are there any protein regions on the protein surface that do not evolve? To answer these questions, we first built phylogenetically-aware models of the patterns of surface and interior substitutions. Employing these models, we found a single coherent pattern of faster evolution on the protein surfaces that characterizes all influenza proteins. The pattern is consistent with the events of inter-species reassortment, the worldwide introduction of the flu vaccine in the early 80’s, as well as the differences caused by the geographic origins of the virus. Next, we developed an automated computational pipeline to comprehensively detect regions of the protein surface residues that were 100% conserved over multiple years and in multiple host species. We identified conserved regions on the surface of 10 influenza proteins spread across all avian, swine, and human strains; with the exception of a small group of isolated strains that affected the conservation of three proteins. Surprisingly, these regions were also unaffected by genetic variation in the pandemic 2009 H1N1 viral population data obtained from deep sequencing experiments. Finally, the conserved regions were intrinsically related to the intra-viral macromolecular interaction interfaces. Our study may provide further insights towards the

  3. Experimental infection with H1N1 European swine influenza virus protects pigs from an infection with the 2009 pandemic H1N1 human influenza virus.

    PubMed

    Busquets, Núria; Segalés, Joaquim; Córdoba, Lorena; Mussá, Tufaria; Crisci, Elisa; Martín-Valls, Gerard E; Simon-Grifé, Meritxell; Pérez-Simó, Marta; Pérez-Maíllo, Monica; Núñez, Jose I; Abad, Francesc X; Fraile, Lorenzo; Pina, Sonia; Majó, Natalia; Bensaid, Albert; Domingo, Mariano; Montoya, María

    2010-01-01

    The recent pandemic caused by human influenza virus A(H1N1) 2009 contains ancestral gene segments from North American and Eurasian swine lineages as well as from avian and human influenza lineages. The emergence of this A(H1N1) 2009 poses a potential global threat for human health and the fact that it can infect other species, like pigs, favours a possible encounter with other influenza viruses circulating in swine herds. In Europe, H1N1, H1N2 and H3N2 subtypes of swine influenza virus currently have a high prevalence in commercial farms. To better assess the risk posed by the A(H1N1) 2009 in the actual situation of swine farms, we sought to analyze whether a previous infection with a circulating European avian-like swine A/Swine/Spain/53207/2004 (H1N1) influenza virus (hereafter referred to as SwH1N1) generated or not cross-protective immunity against a subsequent infection with the new human pandemic A/Catalonia/63/2009 (H1N1) influenza virus (hereafter referred to as pH1N1) 21 days apart. Pigs infected only with pH1N1 had mild to moderate pathological findings, consisting on broncho-interstitial pneumonia. However, pigs inoculated with SwH1N1 virus and subsequently infected with pH1N1 had very mild lung lesions, apparently attributed to the remaining lesions caused by SwH1N1 infection. These later pigs also exhibited boosted levels of specific antibodies. Finally, animals firstly infected with SwH1N1 virus and latter infected with pH1N1 exhibited undetectable viral RNA load in nasal swabs and lungs after challenge with pH1N1, indicating a cross-protective effect between both strains. © INRA, EDP Sciences, 2010.

  4. Influenza A/H1N1 vaccination of patients with SLE: can antimalarial drugs restore diminished response under immunosuppressive therapy?

    PubMed

    Borba, Eduardo F; Saad, Carla G S; Pasoto, Sandra G; Calich, Ana L G; Aikawa, Nadia E; Ribeiro, Ana C M; Moraes, Julio C B; Leon, Elaine P; Costa, Luciana P; Guedes, Lissiane K N; Silva, Clovis A A; Goncalves, Celio R; Fuller, Ricardo; Oliveira, Suzimara A; Ishida, Maria A; Precioso, Alexander R; Bonfa, Eloisa

    2012-06-01

    To assess the efficacy and safety of pandemic 2009 influenza A (H1N1) in SLE under different therapeutic regimens. A total of 555 SLE patients and 170 healthy controls were vaccinated with a single dose of a non-adjuvanted preparation. According to current therapy, patients were initially classified as SLE No Therapy (n = 75) and SLE with Therapy (n = 480). Subsequent evaluations included groups under monotherapy: chloroquine (CQ) (n = 105), prednisone (PRED) ≥20 mg (n = 76), immunosuppressor (IS) (n = 95) and those with a combination of these drugs. Anti-H1N1 titres and seroconversion (SC) rate were evaluated at entry and 21 days post-vaccination. The SLE with Therapy group had lower SC compared with healthy controls (59.0 vs 80.0%; P < 0.0001), whereas the SLE No Therapy group had equivalent SC (72 vs 80.0%; P = 0.18) compared with healthy controls. Further comparison revealed that the SC of SLE No Therapy (72%) was similar to the CQ group (69.5%; P = 0.75), but it was significantly reduced in PRED ≥20 mg (53.9%; P = 0.028), IS (55.7%; P = 0.035) and PRED ≥20 mg + IS (45.4%; P = 0.038). The concomitant use of CQ in each of these later regimens was associated with SC responses comparable with SLE No Therapy group (72%): PRED ≥20 mg + CQ (71.4%; P = 1.00), IS + CQ (65.2%; P = 0.54) and PRED ≥20 mg + IS + CQ (57.4%; P = 0.09). Pandemic influenza A H1N1/2009 vaccine response is diminished in SLE under immunosuppressive therapy and antimalarials seems to restore this immunogenicity. Trial registration. www.clinicaltrials.gov, NCT01151644.

  5. Silent spread of highly pathogenic Avian Influenza H5N1 virus amongst vaccinated commercial layers.

    PubMed

    Poetri, Okti Nadia; Van Boven, Michiel; Claassen, Ivo; Koch, Guus; Wibawan, I Wayan; Stegeman, Arjan; Van den Broek, Jan; Bouma, Annemarie

    2014-12-01

    The aim of this study was to determine whether a single vaccination of commercial layer type chickens with an inactivated vaccine containing highly pathogenic avian influenza virus strain H5N1 A/chicken/Legok/2003, carried out on the farm, was sufficient to protect against infection with the homologous virus strain. A transmission experiment was carried out with pairs of chicken of which one was inoculated with H5N1 virus and the other contact-exposed. Results showed that the majority of the vaccinated birds developed haemagglutination inhibition (HI) titres below 4log2. No clinical signs were observed in the vaccinated birds and virus shedding was limited. However, nearly all vaccinated birds showed a four-fold or higher increase of HI titres after challenge or contact-exposure, which is an indication of infection. This implies that virus transmission most likely has occurred. This study showed that a single vaccination applied under field conditions induced clinical protection, but was insufficient to induce protection against virus transmission, suggesting that silent spread of virus in vaccinated commercial flocks may occur. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. Long lasting immunity in chickens induced by a single shot of influenza vaccine prepared from inactivated non-pathogenic H5N1 virus particles against challenge with a highly pathogenic avian influenza virus.

    PubMed

    Sasaki, Takashi; Kokumai, Norihide; Ohgitani, Toshiaki; Sakamoto, Ryuichi; Takikawa, Noriyasu; Lin, Zhifeng; Okamatsu, Masatoshi; Sakoda, Yoshihiro; Kida, Hiroshi

    2009-08-20

    An influenza vaccine was prepared from inactivated whole particles of the non-pathogenic strain A/duck/Hokkaido/Vac-1/04 (H5N1) virus using an oil adjuvant containing anhydromannitol-octadecenoate-ether (AMOE). The vaccine was injected intramuscularly into five 4-week-old chickens, and 138 weeks after vaccination, they were challenged intranasally with 100 times 50% chicken lethal dose of the highly pathogenic avian influenza (HPAI) virus A/chicken/Yamaguchi/7/04 (H5N1). All 5 chickens survived without exhibiting clinical signs of influenza, although 2 days post-challenge, 3 vaccinated chickens shed limited titres of viruses in laryngopharyngeal swabs.

  7. Antigenic and genomic characterization of human influenza A and B viruses circulating in Argentina after the introduction of influenza A(H1N1)pdm09.

    PubMed

    Russo, Mara L; Pontoriero, Andrea V; Benedetti, Estefania; Czech, Andrea; Avaro, Martin; Periolo, Natalia; Campos, Ana M; Savy, Vilma L; Baumeister, Elsa G

    2014-12-01

    This study was conducted as part of the Argentinean Influenza and other Respiratory Viruses Surveillance Network, in the context of the Global Influenza Surveillance carried out by the World Health Organization (WHO). The objective was to study the activity and the antigenic and genomic characteristics of circulating viruses for three consecutive seasons (2010, 2011 and 2012) in order to investigate the emergence of influenza viral variants. During the study period, influenza virus circulation was detected from January to December. Influenza A and B, and all current subtypes of human influenza viruses, were present each year. Throughout the 2010 post-pandemic season, influenza A(H1N1)pdm09, unexpectedly, almost disappeared. The haemagglutinin (HA) of the A(H1N1)pdm09 viruses studied were segregated in a different genetic group to those identified during the 2009 pandemic, although they were still antigenically closely related to the vaccine strain A/California/07/2009. Influenza A(H3N2) viruses were the predominant strains circulating during the 2011 season, accounting for nearly 76 % of influenza viruses identified. That year, all HA sequences of the A(H3N2) viruses tested fell into the A/Victoria/208/2009 genetic clade, but remained antigenically related to A/Perth/16/2009 (reference vaccine recommended for this three-year period). A(H3N2) viruses isolated in 2012 were antigenically closely related to A/Victoria/361/2011, recommended by the WHO as the H3 component for the 2013 Southern Hemisphere formulation. B viruses belonging to the B/Victoria lineage circulated in 2010. A mixed circulation of viral variants of both B/Victoria and B/Yamagata lineages was detected in 2012, with the former being predominant. A(H1N1)pdm09 viruses remained antigenically closely related to the vaccine virus A/California/7/2009; A(H3N2) viruses continually evolved into new antigenic clusters and both B lineages, B/Victoria/2/87-like and B/Yamagata/16/88-like viruses, were observed

  8. Sensitivity of influenza rapid diagnostic tests to H5N1 and 2009 pandemic H1N1 viruses.

    PubMed

    Sakai-Tagawa, Yuko; Ozawa, Makoto; Tamura, Daisuke; Le, Mai thi Quynh; Nidom, Chairul A; Sugaya, Norio; Kawaoka, Yoshihiro

    2010-08-01

    Simple and rapid diagnosis of influenza is useful for making treatment decisions in the clinical setting. Although many influenza rapid diagnostic tests (IRDTs) are available for the detection of seasonal influenza virus infections, their sensitivity for other viruses, such as H5N1 viruses and the recently emerged swine origin pandemic (H1N1) 2009 virus, remains largely unknown. Here, we examined the sensitivity of 20 IRDTs to various influenza virus strains, including H5N1 and 2009 pandemic H1N1 viruses. Our results indicate that the detection sensitivity to swine origin H1N1 viruses varies widely among IRDTs, with some tests lacking sufficient sensitivity to detect the early stages of infection when the virus load is low.

  9. Protective Efficacy of Recombinant Turkey Herpes Virus (rHVT-H5) and Inactivated H5N1 Vaccines in Commercial Mulard Ducks against the Highly Pathogenic Avian Influenza (HPAI) H5N1 Clade 2.2.1 Virus

    PubMed Central

    Kilany, Walid H.; Safwat, Marwa; Mohammed, Samy M.; Salim, Abdullah; Fasina, Folorunso Oludayo; Fasanmi, Olubunmi G.; Shalaby, Azhar G.; Dauphin, Gwenaelle; Hassan, Mohammed K.; Lubroth, Juan; Jobre, Yilma M.

    2016-01-01

    In Egypt, ducks kept for commercial purposes constitute the second highest poultry population, at 150 million ducks/year. Hence, ducks play an important role in the introduction and transmission of avian influenza (AI) in the Egyptian poultry population. Attempts to control outbreaks include the use of vaccines, which have varying levels of efficacy and failure. To date, the effects of vaccine efficacy has rarely been determined in ducks. In this study, we evaluated the protective efficacy of a live recombinant vector vaccine based on a turkey Herpes Virus (HVT) expressing the H5 gene from a clade 2.2 H5N1 HPAIV strain (A/Swan/Hungary/499/2006) (rHVT-H5) and a bivalent inactivated H5N1 vaccine prepared from clade 2.2.1 and 2.2.1.1 H5N1 seeds in Mulard ducks. A 0.3ml/dose subcutaneous injection of rHVT-H5 vaccine was administered to one-day-old ducklings (D1) and another 0.5ml/dose subcutaneous injection of the inactivated MEFLUVAC was administered at 7 days (D7). Four separate challenge experiments were conducted at Days 21, 28, 35 and 42, in which all the vaccinated ducks were challenged with 106EID50/duck of H5N1 HPAI virus (A/chicken/Egypt/128s/2012(H5N1) (clade 2.2.1) via intranasal inoculation. Maternal-derived antibody regression and post-vaccination antibody immune responses were monitored weekly. Ducks vaccinated at 21, 28, 35 and 42 days with the rHVT-H5 and MEFLUVAC vaccines were protected against mortality (80%, 80%, 90% and 90%) and (50%, 70%, 80% and 90%) respectively, against challenges with the H5N1 HPAI virus. The amount of viral shedding and shedding rates were lower in the rHVT-H5 vaccine groups than in the MEFLUVAC groups only in the first two challenge experiments. However, the non-vaccinated groups shed significantly more of the virus than the vaccinated groups. Both rHVT-H5 and MEFLUVAC provide early protection, and rHVT-H5 vaccine in particular provides protection against HPAI challenge. PMID:27304069

  10. Protective Efficacy of Recombinant Turkey Herpes Virus (rHVT-H5) and Inactivated H5N1 Vaccines in Commercial Mulard Ducks against the Highly Pathogenic Avian Influenza (HPAI) H5N1 Clade 2.2.1 Virus.

    PubMed

    Kilany, Walid H; Safwat, Marwa; Mohammed, Samy M; Salim, Abdullah; Fasina, Folorunso Oludayo; Fasanmi, Olubunmi G; Shalaby, Azhar G; Dauphin, Gwenaelle; Hassan, Mohammed K; Lubroth, Juan; Jobre, Yilma M

    2016-01-01

    In Egypt, ducks kept for commercial purposes constitute the second highest poultry population, at 150 million ducks/year. Hence, ducks play an important role in the introduction and transmission of avian influenza (AI) in the Egyptian poultry population. Attempts to control outbreaks include the use of vaccines, which have varying levels of efficacy and failure. To date, the effects of vaccine efficacy has rarely been determined in ducks. In this study, we evaluated the protective efficacy of a live recombinant vector vaccine based on a turkey Herpes Virus (HVT) expressing the H5 gene from a clade 2.2 H5N1 HPAIV strain (A/Swan/Hungary/499/2006) (rHVT-H5) and a bivalent inactivated H5N1 vaccine prepared from clade 2.2.1 and 2.2.1.1 H5N1 seeds in Mulard ducks. A 0.3ml/dose subcutaneous injection of rHVT-H5 vaccine was administered to one-day-old ducklings (D1) and another 0.5ml/dose subcutaneous injection of the inactivated MEFLUVAC was administered at 7 days (D7). Four separate challenge experiments were conducted at Days 21, 28, 35 and 42, in which all the vaccinated ducks were challenged with 106EID50/duck of H5N1 HPAI virus (A/chicken/Egypt/128s/2012(H5N1) (clade 2.2.1) via intranasal inoculation. Maternal-derived antibody regression and post-vaccination antibody immune responses were monitored weekly. Ducks vaccinated at 21, 28, 35 and 42 days with the rHVT-H5 and MEFLUVAC vaccines were protected against mortality (80%, 80%, 90% and 90%) and (50%, 70%, 80% and 90%) respectively, against challenges with the H5N1 HPAI virus. The amount of viral shedding and shedding rates were lower in the rHVT-H5 vaccine groups than in the MEFLUVAC groups only in the first two challenge experiments. However, the non-vaccinated groups shed significantly more of the virus than the vaccinated groups. Both rHVT-H5 and MEFLUVAC provide early protection, and rHVT-H5 vaccine in particular provides protection against HPAI challenge.

  11. Kinetics of lung lesion development and pro-inflammatory cytokine response in pigs with vaccine-associated enhanced respiratory disease induced by challenge with pandemic (2009) A/H1N1 influenza virus

    USDA-ARS?s Scientific Manuscript database

    The objective of this report was to characterize the enhanced clinical disease and lung lesions observed in pigs vaccinated with inactivated H1N2 swine delta-cluster influenza A virus and challenged with pandemic 2009 A/H1N1 human influenza virus. Eighty-four, six-week-old, crossbred pigs were rand...

  12. Vaccination of domestic ducks against H5N1 HPAI

    USDA-ARS?s Scientific Manuscript database

    Domestic ducks play an important role in the epidemiology of H5N1 and H5N8 highly pathogenic avian influenza (HPAI) viruses, and therefore, successful control of HPAI in ducks is vital for the eradication of the disease in poultry. Vaccination can be used as a tool for supporting eradication by inc...

  13. Immunogenicity of heterologous H5N1 influenza booster vaccination 6 or 18 months after primary vaccination in adults: a randomized controlled clinical trial.

    PubMed

    Langley, Joanne M; Frenette, Louise; Jeanfreau, Robert; Halperin, Scott A; Kyle, Michael; Chu, Laurence; McNeil, Shelly; Dramé, Mamadou; Moris, Philippe; Fries, Louis; Vaughn, David W

    2015-01-15

    Highly pathogenic avian influenza A/H5N1 viruses continue to circulate in birds and infect humans causing serious illness and death. In this randomized, observer-blinded study, adults ≥18 years of age (n=841) received 3.75 or 7.5 μg hemagglutinin antigen (HA) of an AS03-adjuvanted (AS03A or AS03B) A/Indonesia/5/2005 H5N1 (subclade 2.1) vaccine (priming), followed by the same HA dose of AS03-adjuvanted A/turkey/Turkey/1/05 H5N1 (clade 2.2) influenza vaccine as a booster 6 or 18 months after priming; an unprimed group received placebo at Day 0, and 3.75 μg HA of AS03A-adjuvanted booster vaccine at 6 and 18 months. Antibody responses were assessed by hemagglutination-inhibition assay (HI). Microneutralization (MN) antibody and cellular immunoassays were assessed in a subset of participants. Geometric mean titers (GMTs) and seroconversion rates (SCRs) were higher in primed vs. unprimed subjects against the booster strain 10 days following booster vaccination at month 6 and month 18. After the booster at 18 months, the lower limit of the 97.5% confidence interval for the difference in SCR and GMT ratios between primed and unprimed subjects was >15% and >2.0, respectively, fulfilling the primary endpoint criteria for superiority against the booster strain. MN and cellular immune responses corresponded with the immunogenicity seen in HI measures. Adults primed with a dose-sparing oil-in-water adjuvanted H5N1 subclade vaccine had rapid and durable antibody responses to a heterologous subclade boosting vaccine given 6 or 18 months later. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  14. Personal Decision-Making Criteria Related to Seasonal and Pandemic A(H1N1) Influenza-Vaccination Acceptance among French Healthcare Workers

    PubMed Central

    Bouadma, Lila; Barbier, François; Biard, Lucie; Esposito-Farèse, Marina; Le Corre, Bertrand; Macrez, Annick; Salomon, Laurence; Bonnal, Christine; Zanker, Caroline; Najem, Christophe; Mourvillier, Bruno; Lucet, Jean Christophe; Régnier, Bernard; Wolff, Michel; Tubach, Florence

    2012-01-01

    Background Influenza-vaccination rates among healthcare workers (HCW) remain low worldwide, even during the 2009 A(H1N1) pandemic. In France, this vaccination is free but administered on a voluntary basis. We investigated the factors influencing HCW influenza vaccination. Methods In June–July 2010, HCW from wards of five French hospitals completed a cross-sectional survey. A multifaceted campaign aimed at improving vaccination coverage in this hospital group was conducted before and during the 2009 pandemic. Using an anonymous self-administered questionnaire, we assessed the relationships between seasonal (SIV) and pandemic (PIV) influenza vaccinations, and sociodemographic and professional characteristics, previous and current vaccination statuses, and 33 statements investigating 10 sociocognitive domains. The sociocognitive domains describing HCWs' SIV and PIV profiles were analyzed using the classification-and-regression–tree method. Results Of the HCWs responding to our survey, 1480 were paramedical and 401 were medical with 2009 vaccination rates of 30% and 58% for SIV and 21% and 71% for PIV, respectively (p<0.0001 for both SIV and PIV vaccinations). Older age, prior SIV, working in emergency departments or intensive care units, being a medical HCW and the hospital they worked in were associated with both vaccinations; while work shift was associated only with PIV. Sociocognitive domains associated with both vaccinations were self-perception of benefits and health motivation for all HCW. For medical HCW, being a role model was an additional domain associated with SIV and PIV. Conclusions Both vaccination rates remained low. Vaccination mainly depended on self-determined factors and for medical HCW, being a role model. PMID:22848342

  15. Strategy for assessment of the colloidal and biological stability of H1N1 influenza A viruses.

    PubMed

    Hämmerling, Frank; Lorenz-Cristea, Oliver; Baumann, Pascal; Hubbuch, Jürgen

    2017-01-30

    Current influenza vaccines are mostly formulated as liquids which requires a continuous cold chain to maintain the stability of the antigen. For development of vaccines with an increased stability at ambient temperatures, manifold parameters and their influences on the colloidal stability and activity of the antigen have to be understood. This work presents a strategy to examine both, the colloidal stability and the remaining biological activity of H1N1 influenza viruses under various conditions after an incubation of 40 days. H1N1 phase diagrams were generated for several pH values and different initial H1N1 and NaCl concentrations. It was shown that the highest H1N1 recoveries were obtained for pH 6 and that moderate amounts of NaCl are favorable for increased recoveries. In contrast to colloidal stability, the highest remaining HA activity was observed at pH 9. The electrostatic and hydrophobic surface properties of H1N1 were investigated to reveal the mechanisms accounting for the decrease in stability. Secondly, the capability of virus precipitation by polyethylene glycol in combination with determination of surface hydrophobicity was proven to be useful as a predictive tool to rank stability under different conditions. This methodology enables the rapid assessment of aggregation propensity of H1N1 formulations and the influence on the activity of the virus particles and might become a standard tool during the development of vaccine formulations. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Intranasal H5N1 vaccines, adjuvanted with chitosan derivatives, protect ferrets against highly pathogenic influenza intranasal and intratracheal challenge.

    PubMed

    Mann, Alex J; Noulin, Nicolas; Catchpole, Andrew; Stittelaar, Koert J; de Waal, Leon; Veldhuis Kroeze, Edwin J B; Hinchcliffe, Michael; Smith, Alan; Montomoli, Emanuele; Piccirella, Simona; Osterhaus, Albert D M E; Knight, Alastair; Oxford, John S; Lapini, Giulia; Cox, Rebecca; Lambkin-Williams, Rob

    2014-01-01

    We investigated the protective efficacy of two intranasal chitosan (CSN and TM-CSN) adjuvanted H5N1 Influenza vaccines against highly pathogenic avian Influenza (HPAI) intratracheal and intranasal challenge in a ferret model. Six groups of 6 ferrets were intranasally vaccinated twice, 21 days apart, with either placebo, antigen alone, CSN adjuvanted antigen, or TM-CSN adjuvanted antigen. Homologous and intra-subtypic antibody cross-reacting responses were assessed. Ferrets were inoculated intratracheally (all treatments) or intranasally (CSN adjuvanted and placebo treatments only) with clade 1 HPAI A/Vietnam/1194/2004 (H5N1) virus 28 days after the second vaccination and subsequently monitored for morbidity and mortality outcomes. Clinical signs were assessed and nasal as well as throat swabs were taken daily for virology. Samples of lung tissue, nasal turbinates, brain, and olfactory bulb were analysed for the presence of virus and examined for histolopathological findings. In contrast to animals vaccinated with antigen alone, the CSN and TM-CSN adjuvanted vaccines induced high levels of antibodies, protected ferrets from death, reduced viral replication and abrogated disease after intratracheal challenge, and in the case of CSN after intranasal challenge. In particular, the TM-CSN adjuvanted vaccine was highly effective at eliciting protective immunity from intratracheal challenge; serologically, protective titres were demonstrable after one vaccination. The 2-dose schedule with TM-CSN vaccine also induced cross-reactive antibodies to clade 2.1 and 2.2 H5N1 viruses. Furthermore ferrets immunised with TM-CSN had no detectable virus in the respiratory tract or brain, whereas there were signs of virus in the throat and lungs, albeit at significantly reduced levels, in CSN vaccinated animals. This study demonstrated for the first time that CSN and in particular TM-CSN adjuvanted intranasal vaccines have the potential to protect against significant mortality and

  17. Vaccination against pandemic influenza A/H1N1v in England: a real-time economic evaluation.

    PubMed

    Baguelin, Marc; Hoek, Albert Jan Van; Jit, Mark; Flasche, Stefan; White, Peter J; Edmunds, W John

    2010-03-11

    Decisions on how to mitigate an evolving pandemic are technically challenging. We present a real-time assessment of the effectiveness and cost-effectiveness of alternative influenza A/H1N1v vaccination strategies. A transmission dynamic model was fitted to the estimated number of cases in real-time, and used to generate plausible autumn scenarios under different vaccination options. The proportion of these cases by age and risk group leading to primary care consultations, National Pandemic Flu Service consultations, emergency attendances, hospitalisations, intensive care and death was then estimated using existing data from the pandemic. The real-time model suggests that the epidemic will peak in early November, with the peak height being similar in magnitude to the summer wave. Vaccination of the high-risk groups is estimated to prevent about 45 deaths (80% credibility interval 26-67), and save around 2900 QALYs (80% credibility interval 1600-4500). Such a programme is very likely to be cost-effective if the cost of vaccine purchase itself is treated as a sunk cost. Extending vaccination to low-risk individuals is expected to result in more modest gains in deaths and QALYs averted. Extending vaccination to school-age children would be the most cost-effective extension. The early availability of vaccines is crucial in determining the impact of such extensions. There have been a considerable number of cases of H1N1v in England, and so the benefits of vaccination to mitigate the ongoing autumn wave are limited. However, certain groups appear to be at significantly higher risk of complications and deaths, and so it appears both effective and cost-effective to vaccinate them. The United Kingdom was the first country to have a major epidemic in Europe. In countries where the epidemic is not so far advanced vaccination of children may be cost-effective. Similar, detailed, real-time modelling and economic studies could help to clarify the situation.

  18. Molecular epidemiology of influenza A(H1N1)PDM09 hemagglutinin gene circulating in São Paulo State , Brazil: 2016 anticipated influenza season.

    PubMed

    Santos, Katia Corrêa de Oliveira; Silva, Daniela Bernardes Borges da; Sasaki, Norio Augusto; Benega, Margarete Aparecida; Garten, Rebecca; Paiva, Terezinha Maria de

    2017-04-03

    Compared to previous years, seasonal influenza activity commenced early in São Paulo State, Brazil, Southern hemisphere during the 2016 year. In order to investigate the genetic pattern of influenza A(H1N1)pdm09 in the State of Sao Paulo a total of 479 respiratory samples, collected in January by Sentinel Surveillance Units, were screened by real-time RT-PCR. A total of 6 Influenza viruses A(H1N1)pdm09 presenting ct values ≤ 30 were sequenced following phylogenetic analysis. The present study identified the circulation of the new 6B.1 subgroup (A/Sao Paulo/10-118/2016 and A/Sao Paulo/3032/2016). In addition, influenza A(H1N1)pdm09 group 6B has also been identified during January in the State of Sao Paulo. Despite amino acid changes and changes in potential glycosylation motifs, 6B.1 viruses were well inhibited by the reference ferret antiserum against A/California/07/2009 virus, the A(H1N1)pdm09 component of the vaccine for the 2016 influenza season.

  19. Trivalent inactivated influenza vaccine effective against influenza A(H3N2) variant viruses in children during the 2014/15 season, Japan

    PubMed Central

    Sugaya, Norio; Shinjoh, Masayoshi; Kawakami, Chiharu; Yamaguchi, Yoshio; Yoshida, Makoto; Baba, Hiroaki; Ishikawa, Mayumi; Kono, Mio; Sekiguchi, Shinichiro; Kimiya, Takahisa; Mitamura, Keiko; Fujino, Motoko; Komiyama, Osamu; Yoshida, Naoko; Tsunematsu, Kenichiro; Narabayashi, Atsushi; Nakata, Yuji; Sato, Akihiro; Taguchi, Nobuhiko; Fujita, Hisayo; Toki, Machiko; Myokai, Michiko; Ookawara, Ichiro; Takahashi, Takao

    2016-01-01

    The 2014/15 influenza season in Japan was characterised by predominant influenza A(H3N2) activity; 99% of influenza A viruses detected were A(H3N2). Subclade 3C.2a viruses were the major epidemic A(H3N2) viruses, and were genetically distinct from A/New York/39/2012(H3N2) of 2014/15 vaccine strain in Japan, which was classified as clade 3C.1. We assessed vaccine effectiveness (VE) of inactivated influenza vaccine (IIV) in children aged 6 months to 15 years by test-negative case–control design based on influenza rapid diagnostic test. Between November 2014 and March 2015, a total of 3,752 children were enrolled: 1,633 tested positive for influenza A and 42 for influenza B, and 2,077 tested negative. Adjusted VE was 38% (95% confidence intervals (CI): 28 to 46) against influenza virus infection overall, 37% (95% CI: 27 to 45) against influenza A, and 47% (95% CI: -2 to 73) against influenza B. However, IIV was not statistically significantly effective against influenza A in infants aged 6 to 11 months or adolescents aged 13 to 15 years. VE in preventing hospitalisation for influenza A infection was 55% (95% CI: 42 to 64). Trivalent IIV that included A/New York/39/2012(H3N2) was effective against drifted influenza A(H3N2) virus, although vaccine mismatch resulted in low VE. PMID:27784529

  20. Acceptance of H1N1 vaccine among healthcare workers at primary healthcare centres in Abha, KSA.

    PubMed

    Alsaleem, Mohammed Abadi

    2013-04-01

    One of the major concerns related to the pandemic outbreak of H1N1 influenza in 2009 was the cost burden on medical resources, which led to a negative impact on mortality and morbidity. This situation placed healthcare workers (HCWs) in an unusual position of being both the main actors and one of the main targets of the prevention strategies against the 2009 pandemic influenza A (H1N1). The aim of the study was to find out and compare the acceptance of H1N1 vaccine among different categories of primary HCWs in primary healthcare centres in Abha as well as to explore the reasons among them for not accepting the HINI vaccine. A cross-sectional study was conducted including all HCWs serving at primary healthcare centres in Abha. A self-administered validated questionnaire was used to collect data reflecting the intake of H1N1 vaccine and its association with other parameters that may influence the uptake of this vaccine. The overall response rate was 347/402 (86.3%). The age of the participants ranged between 22 and 59 years with a mean of 34.9 years and SD of 8.4 years. The percentage of physicians, nurses and technicians who took the H1N1 vaccination was 32.6, 28 and 10%, respectively. The overall vaccine intake rate was 28.2%. The main reasons given by HCWs for being immunized were personal protection (51%), fear of transmitting disease to their family and relatives (49%) and fear of transmitting the disease to their patients (43.9%). The main reasons given by HCWs for rejecting H1N1 vaccination were fear of side effects (70.3%) and doubts regarding the safety of the vaccine (68.3%). In general, knowledge about H1N1 was insufficient. However, it was better among physicians than among nurses and technicians. The low rate of acceptance of the pandemic vaccine and the insufficient level of knowledge about the H1N1 virus among Saudi HCWs were alarming given that they were considered models for patients and the public.

  1. Comparative Efficacy of Hemagglutinin, Nucleoprotein, and Matrix 2 Protein Gene-Based Vaccination against H5N1 Influenza in Mouse and Ferret

    PubMed Central

    Rao, Srinivas S.; Kong, Wing-Pui; Wei, Chih-Jen; Van Hoeven, Neal; Gorres, J. Patrick; Nason, Martha; Andersen, Hanne; Tumpey, Terrence M.; Nabel, Gary J.

    2010-01-01

    Efforts to develop a broadly protective vaccine against the highly pathogenic avian influenza A (HPAI) H5N1 virus have focused on highly conserved influenza gene products. The viral nucleoprotein (NP) and ion channel matrix protein (M2) are highly conserved among different strains and various influenza A subtypes. Here, we investigate the relative efficacy of NP and M2 compared to HA in protecting against HPAI H5N1 virus. In mice, previous studies have shown that vaccination with NP and M2 in recombinant DNA and/or adenovirus vectors or with adjuvants confers protection against lethal challenge in the absence of HA. However, we find that the protective efficacy of NP and M2 diminishes as the virulence and dose of the challenge virus are increased. To explore this question in a model relevant to human disease, ferrets were immunized with DNA/rAd5 vaccines encoding NP, M2, HA, NP+M2 or HA+NP+M2. Only HA or HA+NP+M2 vaccination conferred protection against a stringent virus challenge. Therefore, while gene-based vaccination with NP and M2 may provide moderate levels of protection against low challenge doses, it is insufficient to confer protective immunity against high challenge doses of H5N1 in ferrets. These immunogens may require combinatorial vaccination with HA, which confers protection even against very high doses of lethal viral challenge. PMID:20352112

  2. Factors Affecting Intention among Students to Be Vaccinated against A/H1N1 Influenza: A Health Belief Model Approach

    PubMed Central

    Teitler-Regev, Sharon; Shahrabani, Shosh; Benzion, Uri

    2011-01-01

    The outbreak of A/H1N1 influenza (henceforth, swine flu) in 2009 was characterized mainly by morbidity rates among young people. This study examined the factors affecting the intention to be vaccinated against the swine flu among students in Israel. Questionnaires were distributed in December 2009 among 387 students at higher-education institutions. The research questionnaire included sociodemographic characteristics and Health Belief Model principles. The results show that the factors positively affecting the intention to take the swine flu vaccine were past experience with seasonal flu shot and three HBM categories: higher levels of perceived susceptibility for catching the illness, perceived seriousness of illness, and lower levels of barriers. We conclude that offering the vaccine at workplaces may raise the intention to take the vaccine among young people in Israel. PMID:22229099

  3. Anti-neuraminidase antibodies against pandemic A/H1N1 influenza viruses in healthy and influenza-infected individuals.

    PubMed

    Desheva, Yulia; Sychev, Ivan; Smolonogina, Tatiana; Rekstin, Andrey; Ilyushina, Natalia; Lugovtsev, Vladimir; Samsonova, Anastasia; Go, Aleksey; Lerner, Anna

    2018-01-01

    The main objective of the study was to evaluate neuraminidase inhibiting (NI) antibodies against A/H1N1pdm09 influenza viruses in the community as a whole and after infection. We evaluated NI serum antibodies against A/California/07/09(H1N1)pdm and A/South Africa/3626/2013(H1N1)pdm in 134 blood donors of different ages using enzyme-linked lectin assay and in 15 paired sera from convalescents with laboratory confirmed influenza. The neuraminidase (NA) proteins of both A/H1N1pdm09 viruses had minimal genetic divergence, but demonstrated different enzymatic and antigenic properties. 5.2% of individuals had NI antibody titers ≥1:20 against A/South Africa/3626/2013(H1N1)pdm compared to 53% of those who were positive to A/California/07/2009(H1N1)pdm NA. 2% of individuals had detectable NI titers against A/South Africa/3626/13(H1N1)pdm and 47.3% were positive to A/California/07/2009(H1N1)pdm NA among participants negative to hemagglutinin (HA) of A/H1N1pdm09 but positive to seasonal A/H1N1. The lowest NI antibody levels to both A/H1N1pdm09 viruses were detected in individuals born between 1956 and 1968. Our data suggest that NI antibodies against A/South Africa/3626/13 (H1N1)pdm found in the blood donors could have resulted from direct infection with a new antigenic A/H1N1pdm09 variant rather than from cross-reaction as a result of contact with previously circulating seasonal A/H1N1 variants. The immune responses against HA and NA were formed simultaneously right after natural infection with A/H1N1pdm09. NI antibodies correlated with virus-neutralizing antibodies when acquired shortly after influenza infection. A group of middle-aged patients with the lowest level of anti-NA antibodies against A/California/07/2009 (H1N1)pdm was identified, indicating the highest-priority vaccination against A/H1N1pdm09 viruses.

  4. Anti-neuraminidase antibodies against pandemic A/H1N1 influenza viruses in healthy and influenza-infected individuals

    PubMed Central

    Sychev, Ivan; Smolonogina, Tatiana; Rekstin, Andrey; Ilyushina, Natalia; Lugovtsev, Vladimir; Samsonova, Anastasia; Go, Aleksey; Lerner, Anna

    2018-01-01

    The main objective of the study was to evaluate neuraminidase inhibiting (NI) antibodies against A/H1N1pdm09 influenza viruses in the community as a whole and after infection. We evaluated NI serum antibodies against A/California/07/09(H1N1)pdm and A/South Africa/3626/2013(H1N1)pdm in 134 blood donors of different ages using enzyme-linked lectin assay and in 15 paired sera from convalescents with laboratory confirmed influenza. The neuraminidase (NA) proteins of both A/H1N1pdm09 viruses had minimal genetic divergence, but demonstrated different enzymatic and antigenic properties. 5.2% of individuals had NI antibody titers ≥1:20 against A/South Africa/3626/2013(H1N1)pdm compared to 53% of those who were positive to A/California/07/2009(H1N1)pdm NA. 2% of individuals had detectable NI titers against A/South Africa/3626/13(H1N1)pdm and 47.3% were positive to A/California/07/2009(H1N1)pdm NA among participants negative to hemagglutinin (HA) of A/H1N1pdm09 but positive to seasonal A/H1N1. The lowest NI antibody levels to both A/H1N1pdm09 viruses were detected in individuals born between 1956 and 1968. Our data suggest that NI antibodies against A/South Africa/3626/13 (H1N1)pdm found in the blood donors could have resulted from direct infection with a new antigenic A/H1N1pdm09 variant rather than from cross-reaction as a result of contact with previously circulating seasonal A/H1N1 variants. The immune responses against HA and NA were formed simultaneously right after natural infection with A/H1N1pdm09. NI antibodies correlated with virus-neutralizing antibodies when acquired shortly after influenza infection. A group of middle-aged patients with the lowest level of anti-NA antibodies against A/California/07/2009 (H1N1)pdm was identified, indicating the highest-priority vaccination against A/H1N1pdm09 viruses. PMID:29742168

  5. Fitness of Pandemic H1N1 and Seasonal influenza A viruses during Co-infection: Evidence of competitive advantage of pandemic H1N1 influenza versus seasonal influenza.

    PubMed

    Perez, Daniel Roberto; Sorrell, Erin; Angel, Matthew; Ye, Jianqiang; Hickman, Danielle; Pena, Lindomar; Ramirez-Nieto, Gloria; Kimble, Brian; Araya, Yonas

    2009-08-24

    On June 11, 2009 the World Health Organization (WHO) declared a new H1N1 influenza pandemic. This pandemic strain is as transmissible as seasonal H1N1 and H3N2 influenza A viruses. Major concerns facing this pandemic are whether the new virus will replace, co-circulate and/or reassort with seasonal H1N1 and/or H3N2 human strains. Using the ferret model, we investigated which of these three possibilities were most likely favored. Our studies showed that the current pandemic virus is more transmissible than, and has a biological advantage over, prototypical seasonal H1 or H3 strains.

  6. Increased risk of narcolepsy in children and adults after pandemic H1N1 vaccination in France.

    PubMed

    Dauvilliers, Yves; Arnulf, Isabelle; Lecendreux, Michel; Monaca Charley, Christelle; Franco, Patricia; Drouot, Xavier; d'Ortho, Marie-Pia; Launois, Sandrine; Lignot, Séverine; Bourgin, Patrice; Nogues, Béatrice; Rey, Marc; Bayard, Sophie; Scholz, Sabine; Lavault, Sophie; Tubert-Bitter, Pascale; Saussier, Cristel; Pariente, Antoine

    2013-08-01

    An increased incidence of narcolepsy in children was detected in Scandinavian countries where pandemic H1N1 influenza ASO3-adjuvanted vaccine was used. A campaign of vaccination against pandemic H1N1 influenza was implemented in France using both ASO3-adjuvanted and non-adjuvanted vaccines. As part of a study considering all-type narcolepsy, we investigated the association between H1N1 vaccination and narcolepsy with cataplexy in children and adults compared with matched controls; and compared the phenotype of narcolepsy with cataplexy according to exposure to the H1N1 vaccination. Patients with narcolepsy-cataplexy were included from 14 expert centres in France. Date of diagnosis constituted the index date. Validation of cases was performed by independent experts using the Brighton collaboration criteria. Up to four controls were individually matched to cases according to age, gender and geographic location. A structured telephone interview was performed to collect information on medical history, past infections and vaccinations. Eighty-five cases with narcolepsy-cataplexy were included; 23 being further excluded regarding eligibility criteria. Of the 62 eligible cases, 59 (64% males, 57.6% children) could be matched with 135 control subjects. H1N1 vaccination was associated with narcolepsy-cataplexy with an odds ratio of 6.5 (2.1-19.9) in subjects aged<18 years, and 4.7 (1.6-13.9) in those aged 18 and over. Sensitivity analyses considering date of referral for diagnosis or the date of onset of symptoms as the index date gave similar results, as did analyses focusing only on exposure to ASO3-adjuvanted vaccine. Slight differences were found when comparing cases with narcolepsy-cataplexy exposed to H1N1 vaccination (n=32; mostly AS03-adjuvanted vaccine, n=28) to non-exposed cases (n=30), including shorter delay of diagnosis and a higher number of sleep onset rapid eye movement periods for exposed cases. No difference was found regarding history of infections. In

  7. A duplex real-time RT-PCR assay for detecting H5N1 avian influenza virus and pandemic H1N1 influenza virus.

    PubMed

    Kang, Xiao-ping; Jiang, Tao; Li, Yong-qiang; Lin, Fang; Liu, Hong; Chang, Guo-hui; Zhu, Qing-yu; Qin, E-de; Qin, Cheng-feng; Yang, Yin-hui

    2010-06-02

    A duplex real-time reverse transcriptase polymerase chain reaction (RT-PCR) assay was improved for simultaneous detection of highly pathogenic H5N1 avian influenza virus and pandemic H1N1 (2009) influenza virus, which is suitable for early diagnosis of influenza-like patients and for epidemiological surveillance. The sensitivity of this duplex real-time RT-PCR assay was 0.02 TCID50 (50% tissue culture infective dose) for H5N1 and 0.2 TCID50 for the pandemic H1N1, which was the same as that of each single-target RT-PCR for pandemic H1N1 and even more sensitive for H5N1 with the same primers and probes. No cross reactivity of detecting other subtype influenza viruses or respiratory tract viruses was observed. Two hundred and thirty-six clinical specimens were tested by comparing with single real-time RT-PCR and result from the duplex assay was 100% consistent with the results of single real-time RT-PCR and sequence analysis.

  8. Adverse events following pandemic influenza A (H1N1) 2009 monovalent and seasonal influenza vaccinations during the 2009-2010 season in the active component U.S. military and civilians aged 17-44years reported to the Vaccine Adverse Event Reporting System.

    PubMed

    Bardenheier, Barbara H; Duderstadt, Susan K; Engler, Renata J M; McNeil, Michael M

    2016-08-17

    No comparative review of Vaccine Adverse Event Reporting System (VAERS) submissions following pandemic influenza A (H1N1) 2009 and seasonal influenza vaccinations during the pandemic season among U.S. military personnel has been published. We compared military vs. civilian adverse event reporting rates. Adverse events (AEs) following vaccination were identified from VAERS for adults aged 17-44years after pandemic (monovalent influenza [MIV], and seasonal (trivalent inactivated influenza [IIV3], live attenuated influenza [LAIV3]) vaccines. Military vaccination coverage was provided by the Department of Defense's Defense Medical Surveillance System. Civilian vaccination coverage was estimated using data from the National 2009 H1N1 Flu Survey and the Behavioral Risk Factor Surveillance System survey. Vaccination coverage was more than four times higher for MIV and more than twenty times higher for LAIV3 in the military than in the civilian population. The reporting rate of serious AE reports following MIV in service personnel (1.19 per 100,000) was about half that reported by the civilian population (2.45 per 100,000). Conversely, the rate of serious AE reports following LAIV3 among service personnel (1.32 per 100,000) was more than twice that of the civilian population. Although fewer military AEs following MIV were reported overall, the rate of Guillain-Barré Syndrome (GBS) (4.01 per million) was four times greater than that in the civilian population. (1.04 per million). Despite higher vaccination coverage in service personnel, the rate of serious AEs following MIV was about half that in civilians. The rate of GBS reported following MIV was higher in the military. Published by Elsevier Ltd.

  9. Safety and immunogenicity of adjuvanted inactivated split-virion and whole-virion influenza A (H5N1) vaccines in children: a phase I-II randomized trial.

    PubMed

    Wu, Jiang; Liu, Shu-Zhen; Dong, Shan-Shan; Dong, Xiao-Ping; Zhang, Wu-Li; Lu, Min; Li, Chang-Gui; Zhou, Ji-Chen; Fang, Han-Hua; Liu, Yan; Liu, Li-Ying; Qiu, Yuan-Zheng; Gao, Qiang; Zhang, Xiao-Mei; Chen, Jiang-Ting; Zhong, Xiang; Yin, Wei-Dong; Feng, Zi-Jian

    2010-08-31

    Highly pathogenic avian influenza A virus H5N1 has the potential to cause a pandemic. Many prototype pandemic influenza A (H5N1) vaccines had been developed and well evaluated in adults in recent years. However, data in children are limited. Herein we evaluate the safety and immunogenicity of adjuvanted split-virion and whole-virion H5N1 vaccines in children. An open-labelled phase I trial was conducted in children aged 3-11 years to receive aluminum-adjuvated, split-virion H5N1 vaccine (5-30 microg) and in children aged 12-17 years to receive aluminum-adjuvated, whole-virion H5N1 vaccine (5-15 microg). Safety of the two formulations was assessed. Then a randomized phase II trial was conducted, in which 141 children aged 3-11 years received the split-virion vaccine (10 or 15 microg) and 280 children aged 12-17 years received the split-virion vaccine (10-30 microg) or the whole-virion vaccine (5 microg). Serum samples were collected for hemagglutination-inhibition (HI) assays. 5-15 microg adjuvated split-virion vaccines were well tolerated in children aged 3-11 years and 5-30 microg adjuvated split-virion vaccines and 5 microg adjuvated whole-virion vaccine were well tolerated in children aged 12-17 years. Most local and systemic reactions were mild or moderate. Before vaccination, all participants were immunologically naïve to H5N1 virus. Immune responses were induced after the first dose and significantly boosted after the second dose. In 3-11 years children, the 10 and 15 microg split-virion vaccine induced similar responses with 55% seroconversion and seroprotection (HI titer >or=1:40) rates. In 12-17 years children, the 30 microg split-virion vaccine induced the highest immune response with 71% seroconversion and seroprotection rates. The 5 microg whole-virion vaccine induced higher response than the 10 microg split-virion vaccine did. The aluminum-adjuvanted, split-virion prototype pandemic influenza A (H5N1) vaccine showed good safety and immunogenicity in

  10. Higher titers of some H5N1 and recent human H1N1 and H3N2 influenza viruses in Mv1 Lu vs. MDCK cells

    PubMed Central

    2011-01-01

    Background The infectivity of influenza A viruses can differ among the various primary cells and continuous cell lines used for such measurements. Over many years, we observed that all things equal, the cytopathic effects caused by influenza A subtype H1N1, H3N2, and H5N1 viruses were often detected earlier in a mink lung epithelial cell line (Mv1 Lu) than in MDCK cells. We asked whether virus yields as measured by the 50% tissue culture infectious dose and plaque forming titer also differed in MDCK and Mv1 Lu cells infected by the same influenza virus subtypes. Results The 50% tissue culture infectious dose and plaque forming titer of many influenza A subtype H1N1, H3N2, and H5N1 viruses was higher in Mv1 Lu than in MDCK cells. Conclusions The yields of influenza subtype H1N1, H3N2, and H5N1 viruses can be higher in Mv1 Lu cells than in MDCK cells. PMID:21314955

  11. Randomized controlled ferret study to assess the direct impact of 2008-09 trivalent inactivated influenza vaccine on A(H1N1)pdm09 disease risk.

    PubMed

    Skowronski, Danuta M; Hamelin, Marie-Eve; De Serres, Gaston; Janjua, Naveed Z; Li, Guiyun; Sabaiduc, Suzana; Bouhy, Xavier; Couture, Christian; Leung, Anders; Kobasa, Darwyn; Embury-Hyatt, Carissa; de Bruin, Erwin; Balshaw, Robert; Lavigne, Sophie; Petric, Martin; Koopmans, Marion; Boivin, Guy

    2014-01-01

    During spring-summer 2009, several observational studies from Canada showed increased risk of medically-attended, laboratory-confirmed A(H1N1)pdm09 illness among prior recipients of 2008-09 trivalent inactivated influenza vaccine (TIV). Explanatory hypotheses included direct and indirect vaccine effects. In a randomized placebo-controlled ferret study, we tested whether prior receipt of 2008-09 TIV may have directly influenced A(H1N1)pdm09 illness. Thirty-two ferrets (16/group) received 0.5 mL intra-muscular injections of the Canadian-manufactured, commercially-available, non-adjuvanted, split 2008-09 Fluviral or PBS placebo on days 0 and 28. On day 49 all animals were challenged (Ch0) with A(H1N1)pdm09. Four ferrets per group were randomly selected for sacrifice at day 5 post-challenge (Ch+5) and the rest followed until Ch+14. Sera were tested for antibody to vaccine antigens and A(H1N1)pdm09 by hemagglutination inhibition (HI), microneutralization (MN), nucleoprotein-based ELISA and HA1-based microarray assays. Clinical characteristics and nasal virus titers were recorded pre-challenge then post-challenge until sacrifice when lung virus titers, cytokines and inflammatory scores were determined. Baseline characteristics were similar between the two groups of influenza-naïve animals. Antibody rise to vaccine antigens was evident by ELISA and HA1-based microarray but not by HI or MN assays; virus challenge raised antibody to A(H1N1)pdm09 by all assays in both groups. Beginning at Ch+2, vaccinated animals experienced greater loss of appetite and weight than placebo animals, reaching the greatest between-group difference in weight loss relative to baseline at Ch+5 (7.4% vs. 5.2%; p = 0.01). At Ch+5 vaccinated animals had higher lung virus titers (log-mean 4.96 vs. 4.23pfu/mL, respectively; p = 0.01), lung inflammatory scores (5.8 vs. 2.1, respectively; p = 0.051) and cytokine levels (p>0.05). At Ch+14, both groups had recovered. Findings in influenza

  12. Glycosylations in the globular head of the hemagglutinin protein modulate the virulence and antigenic properties of the H1N1 influenza viruses

    PubMed Central

    Medina, Rafael A.; Stertz, Silke; Manicassamy, Balaji; Zimmermann, Petra; Sun, Xiangjie; Albrecht, Randy A.; Uusi-Kerttula, Hanni; Zagordi, Osvaldo; Belshe, Robert B.; Frey, Sharon E.; Eggink, Dirk; Tumpey, Terrence M.; García-Sastre, Adolfo

    2014-01-01

    The global spread of the 2009 pandemic H1N1 (pH1N1) virus in humans increases the likelihood that this influenza virus strain could undergo antigenic drift in the coming years. Previous seasonal H1N1 and H3N2 influenza strains acquired additional glycosylations in the globular head of their hemagglutinin (HA) proteins as they evolved over time; these are believed to shield antigenically relevant regions. We used influenza A/Netherlands/602/2009 recombinant (rpH1N1) viruses to which we added additional HA glycosylation sites reflecting their temporal appearance in previous seasonal H1N1 viruses. Additional glycosylations resulted in substantial attenuation in mice and ferrets, while deleting HA glycosylation sites from a pre-pandemic 1991 seasonal H1N1 influenza virus resulted in increased pathogenicity in mice. Sera from mice infected with wild type (WT) rpH1N1 virus showed a considerable loss of HA inhibitory (HI) activity against rpH1N1 viruses glycosylated at sites 144 or 144-172, indicating that the polyclonal antibody response elicited by WT rpH1N1 HA seems to be directed against an immunodominant region, likely site Sa, shielded by glycosylation at 144. Sera from humans vaccinated with the pH1N1 inactivated vaccine also showed reduced activity against the 144 and 144-172 mutant viruses. Remarkably, the HI activity of sera from virus-infected mice demonstrated that glycosylation at position 144 resulted in the induction of a broader polyclonal response able to cross-neutralize all WT and glycosylation mutant pH1N1 viruses. Mice infected with a recent seasonal virus in which glycosylation sites 71, 142 and 177 were removed, elicited antibodies that protected against challenge with the antigenically distant pH1N1 virus. Thus, acquisition of glycosylation sites in the HA of H1N1 human influenza viruses not only affects their pathogenicity and ability to escape from polyclonal antibodies elicited by previous influenza virus strains, but also their ability to

  13. Adult Influenza A (H1N1) Related Encephalitis: A Case Report.

    PubMed

    Midha, Devinder; Kumar, Arun; Vasudev, Pratibha; Iqbal, Zafar Ahmad; Mandal, Amit Kumar

    2018-05-01

    The year 2009-2010 saw H1N1 influenza outbreaks occurring in almost all countries of the world, causing the WHO to declare it a pandemic of an alert level of 6. In India, H1N1 influenza outbreaks were again reported in late 2014 and early 2015. Since then, sporadic cases of H1N1 influenza have been reported. H1N1 influenza usually presents itself with respiratory tract symptoms. In a minority of patients, abdominal symptoms may occur as well. Acute influenza-associated encephalopathy/encephalitis mostly occurs in the pediatric population, whereas in adults, it is a rare complication. The incidence of neurological complications appears to have increased after the 2009 H1N1 influenza A virus pandemic. We would like to draw attention to an adult patient case who initially presented with respiratory symptoms but then deteriorated and developed encephalitis, which is rarely reported. As per literature reviewed by Victoria Bangualid and Judith Berger on PubMed, only 21 cases of neurological complications were found in adult influenza A patients, out of whom 8 had encephalopathy.

  14. 2009 pandemic influenza A (H1N1) in pregnant women requiring intensive care - New York City, 2009.

    PubMed

    2010-03-26

    Pregnant women are at increased risk for severe illness and complications from infection with seasonal influenza and 2009 pandemic influenza A (H1N1). To characterize the severity of 2009 H1N1 infection in pregnant women, the New York City Department of Health and Mental Hygiene (DOHMH) conducted active and passive surveillance for cases of 2009 H1N1 infection in pregnant women requiring intensive care. This report summarizes the results of that surveillance, which found that, during 2009, 16 pregnant women and one who was postpartum were admitted to New York City intensive-care units (ICUs). Two women died. Of the 17 women, 12 had no recognized risk factors for severe influenza complications other than pregnancy. All 17 women received antiviral treatment with oseltamivir; however, treatment was initiated or=5 days after symptom onset in four women. Because initiation of antiviral treatment influenza-like symptoms, and health-care providers should initiate empiric antiviral therapy for these women as soon as possible, even if >2 days after symptom onset. Health departments and health-care providers should educate pregnant and postpartum women regarding the risks posed by influenza and highlight the effectiveness and safety of influenza vaccination. Obstetricians and other health-care providers should offer influenza vaccination to their pregnant patients.

  15. Heterogeneity of T Cell Responses to Pandemic pH1N1 Monovalent Vaccine in HIV-Infected Pregnant Women.

    PubMed

    Weinberg, Adriana; Muresan, Petronella; Richardson, Kelly; Fenton, Terence; Dominguez, Teresa; Bloom, Anthony; Watts, D Heather; Abzug, Mark J; Nachman, Sharon A; Levin, Myron J

    2015-11-01

    We investigated the Th1 protective and regulatory T and B cell (Treg and Breg) responses to pH1N1 monovalent influenza vaccine (IIV1) in HIV-infected pregnant women on combination antiretroviral therapy (cART). Peripheral blood mononuclear cells (PBMCs) from 52 study participants were cryopreserved before and after vaccination and analyzed by flow cytometry. pH1N1-specific Th1, Treg, and Breg responses were measured in PBMCs after in vitro stimulation with pH1N1 and control antigen. The cohort analysis did not detect changes in pH1N1-Th1, Treg, or Breg subsets postvaccination. However, individual analyses distinguished subjects who mounted vigorous Th1 responses postvaccination from others who did not. Postvaccination, high pH1N1-Th1 correlated with high pH1N1-Treg and Breg responses, suggesting that low influenza effector responses did not result from excessive vaccine-induced immune regulation. High postvaccination pH1N1-Th1 responses correlated with baseline high PHA- and pH1N1-IFN-γ ELISpot and circulating CD4(+)CD39(+)% and CD8(+)CD39(+)% Treg, with low CD8(+) cell numbers and CD19(+)FOXP3(+)% Breg, but not with CD4(+) cell numbers or HIV viral load. These data highlight the heterogeneity of T cell responses to vaccines in HIV-infected individuals on cART. Predictors of robust Th1 responses to IIV include CD8(+) cell numbers, T cell functionality, and circulating Breg and Treg.

  16. Evaluating interest in an influenza A(H5N1) vaccine among laboratory workers who work with highly-pathogenic avian influenza viruses in the United States.

    PubMed

    Russell, Kate E; Bresee, J S; Katz, J M; Olsen, S J

    2018-01-04

    Highly pathogenic avian influenza A (HPAI) viruses found in poultry and wild birds occasionally infect humans and can cause serious disease. In 2014, the Advisory Committee on Immunization Practices (ACIP) reviewed data from one licensed ASO3-adjuvanted influenza A(H5N1) vaccine for consideration of use during inter-pandemic periods among persons with occupational exposure. To guide vaccine policy decisions, we conducted a survey of laboratory workers to assess demand for HPAI vaccination. We designed an anonymous web survey (EpiInfo 7.0) to collect information on demographics, type of work and time spent with HPAI viruses, and interest in HPAI vaccination. Eligible participants were identified from 42 entities registered with United States Department of Agriculture's Agricultural Select Agent program in 2016 and emailed electronic surveys. Personnel with Biosafety Level 3 enhanced (BSL-3E) laboratory access were surveyed. Descriptive analysis was performed. Overall, 131 responses were received from 33 principal investigators, 26 research scientists, 24 technicians, 15 postdoctoral fellows, 6 students, and 27 others. The estimated response rate was 15% among the laboratory personnel of responding principal investigators. One hundred respondents reported working in a BSL-3E area where HPAI experiments occurred with a mean time of 5.1-11.7 h per week. Overall, 49% were interested in receiving an A(H5N1) vaccine. By role, interest was highest among students (80%) and among those who spent >50% of their time in a BSL-3E area (64%). Most (61%) of those who said they might be or were not interested in vaccine believed it would not provide additional protection to current safety practices. Half of responding laboratory workers was interested in receiving an influenza A(H5N1) vaccine. HPAI vaccination of laboratory workers at risk of occupational exposure could be used along with existing safety practices to protect this population. Published by Elsevier Ltd.

  17. Molecular epidemiology of influenza A(H1N1)PDM09 hemagglutinin gene circulating in São Paulo State , Brazil: 2016 anticipated influenza season

    PubMed Central

    Santos, Katia Corrêa de Oliveira; da Silva, Daniela Bernardes Borges; Sasaki, Norio Augusto; Benega, Margarete Aparecida; Garten, Rebecca; de Paiva, Terezinha Maria

    2017-01-01

    ABSTRACT Compared to previous years, seasonal influenza activity commenced early in São Paulo State, Brazil, Southern hemisphere during the 2016 year. In order to investigate the genetic pattern of influenza A(H1N1)pdm09 in the State of Sao Paulo a total of 479 respiratory samples, collected in January by Sentinel Surveillance Units, were screened by real-time RT-PCR. A total of 6 Influenza viruses A(H1N1)pdm09 presenting ct values ≤ 30 were sequenced following phylogenetic analysis. The present study identified the circulation of the new 6B.1 subgroup (A/Sao Paulo/10-118/2016 and A/Sao Paulo/3032/2016). In addition, influenza A(H1N1)pdm09 group 6B has also been identified during January in the State of Sao Paulo. Despite amino acid changes and changes in potential glycosylation motifs, 6B.1 viruses were well inhibited by the reference ferret antiserum against A/California/07/2009 virus, the A(H1N1)pdm09 component of the vaccine for the 2016 influenza season. PMID:28380120

  18. Intranasal co-administration of 1,8-cineole with influenza vaccine provide cross-protection against influenza virus infection.

    PubMed

    Li, Yun; Xu, Yu-Ling; Lai, Yan-Ni; Liao, Shang-Hui; Liu, Ni; Xu, Pei-Ping

    2017-10-15

    Vaccination is the most efficient means for protection against influenza. However, the various vaccines have low efficacy to protect against pandemic strains because of antigenic drift and recombination of influenza virus. Adjuvant therapy is one of the attempts to improve influenza vaccine effective cross-protection against influenza virus infection. Our previous study confirmed that 1,8-cineole inhibits the NF-κB, reduces pro-inflammatory cytokines, and relieves the pathological changes of viral pneumonia in mice infected with influenza virus. 1,8-cineole, administered via intranasal (i.n.) route, may also have the capacity to be an adjuvant of the influenza vaccine. This study was designed to investigate the potential use of i.n. co-administration of 1,8-cineole, a major component of the Eucalyptus essential oils, with influenza vaccine and whether could provide cross-protection against influenza virus infection in a mouse model. I.n. co-administration of 1,8-cineole in two doses (6.25 and 12.5 mg/kg) with influenza vaccine was investigated in a mouse model in order to see whether it could provide cross-protection against influenza virus infection. The mice were intranasally immunized three times at the 0, 7 and 14 day with vaccine containing 0.2 µg hemagglutinin (HA) and/or without 1,8-cineole. Seven days after the 3rd immunization dose, the mice were infected with 50 µl of 15 LD 50 (50% mouse lethal dose) influenza virus A/FM/1/47 (H1N1). On day 6 post-infection, 10 mice per group were sacrificed to collect samples, to take the body weight and lung, and detect the viral load, pathological changes in the lungs and antibody, etc. The collected samples included blood serum and nasal lavage fluids. In addition, the survival experiments were carried out  to investigate the survival of mice. Mice i.n. inoculated with influenza vaccine and 12.5 mg/kg 1,8-cineole increased the production of influenza-specific serum immunoglobulin (Ig) G2a antibodies

  19. Avian influenza A (H5N1).

    PubMed

    de Jong, Menno D; Hien, Tran Tinh

    2006-01-01

    Since their reemergence in 2003, highly pathogenic avian influenza A (H5N1) viruses have reached endemic levels among poultry in several southeast Asian countries and have caused a still increasing number of more than 100 reported human infections with high mortality. These developments have ignited global fears of an imminent influenza pandemic. The current knowledge of the virology, clinical spectrum, diagnosis and treatment of human influenza H5N1 virus infections is reviewed herein.

  20. Challenge for One Health: Co-Circulation of Zoonotic H5N1 and H9N2 Avian Influenza Viruses in Egypt.

    PubMed

    Kim, Shin-Hee

    2018-03-09

    Highly pathogenic avian influenza (HPAI) H5N1 viruses are currently endemic in poultry in Egypt. Eradication of the viruses has been unsuccessful due to improper application of vaccine-based control strategies among other preventive measures. The viruses have evolved rapidly with increased bird-to-human transmission efficacy, thus affecting both animal and public health. Subsequent spread of potentially zoonotic low pathogenic avian influenza (LPAI) H9N2 in poultry has also hindered efficient control of avian influenza. The H5N1 viruses acquired enhanced bird-to-human transmissibility by (1) altering amino acids in hemagglutinin (HA) that enable binding affinity to human-type receptors, (2) loss of the glycosylation site and 130 loop in the HA protein and (3) mutation of E627K in the PB2 protein to enhance viral replication in mammalian hosts. The receptor binding site of HA of Egyptian H9N2 viruses has been shown to contain the Q234L substitution along with a H191 mutation, which can increase human-like receptor specificity. Therefore, co-circulation of H5N1 and H9N2 viruses in poultry farming and live bird markets has increased the risk of human exposure, resulting in complication of the epidemiological situation and raising a concern for potential emergence of a new influenza A virus pandemic. For efficient control of infection and transmission, the efficacy of vaccine and vaccination needs to be improved with a comprehensive control strategy, including enhanced biosecurity, education, surveillance, rapid diagnosis and culling of infected poultry.

  1. Challenge for One Health: Co-Circulation of Zoonotic H5N1 and H9N2 Avian Influenza Viruses in Egypt

    PubMed Central

    2018-01-01

    Highly pathogenic avian influenza (HPAI) H5N1 viruses are currently endemic in poultry in Egypt. Eradication of the viruses has been unsuccessful due to improper application of vaccine-based control strategies among other preventive measures. The viruses have evolved rapidly with increased bird-to-human transmission efficacy, thus affecting both animal and public health. Subsequent spread of potentially zoonotic low pathogenic avian influenza (LPAI) H9N2 in poultry has also hindered efficient control of avian influenza. The H5N1 viruses acquired enhanced bird-to-human transmissibility by (1) altering amino acids in hemagglutinin (HA) that enable binding affinity to human-type receptors, (2) loss of the glycosylation site and 130 loop in the HA protein and (3) mutation of E627K in the PB2 protein to enhance viral replication in mammalian hosts. The receptor binding site of HA of Egyptian H9N2 viruses has been shown to contain the Q234L substitution along with a H191 mutation, which can increase human-like receptor specificity. Therefore, co-circulation of H5N1 and H9N2 viruses in poultry farming and live bird markets has increased the risk of human exposure, resulting in complication of the epidemiological situation and raising a concern for potential emergence of a new influenza A virus pandemic. For efficient control of infection and transmission, the efficacy of vaccine and vaccination needs to be improved with a comprehensive control strategy, including enhanced biosecurity, education, surveillance, rapid diagnosis and culling of infected poultry. PMID:29522492

  2. Long-term persistence of humoral and cellular immune responses induced by an AS03A-adjuvanted H1N1 2009 influenza vaccine: an open-label, randomized study in adults aged 18-60 years and older.

    PubMed

    Van Damme, Pierre; Kafeja, Froukje; Bambure, Vinod; Hanon, Emmanuel; Moris, Philippe; Roman, François; Gillard, Paul

    2013-07-01

    This manuscript presents data on the persistence of Hemagglutination Inhibition (HI) immune response against the A/California/7/2009 strain, six and 12 mo after adults received one dose (n = 138) or two doses (n = 102; 21 d apart) of a 3.75 µg Hemagglutinin antigen AS03-adjuvanted H1N1 2009 vaccine (NCT00968526). Two hundred forty subjects (18-60 y: 120;>60 y: 120) were vaccinated. Immunogenicity end points were based on the European licensure criteria for pandemic influenza vaccines. Exploratory analyses assessed the cell-mediated immune response (CMI) up to Month 12 and the influence of previous influenza vaccination on persistence of immune response. At Month 6, the CHMP criteria were met in subjects aged 18-60 y who received one or two vaccine doses and in subjects aged>60 y who received two vaccine doses. At Month 12, the CHMP criteria were met only in subjects aged 18-60 y who received two vaccine doses. Persistence of HI immune response against the vaccine strain was higher in subjects without prior influenza vaccination. Exploratory analyses showed that two doses of the H1N1 2009 vaccine induced persistence of H1N1-specific CD4+ T cells up to Month 6 and memory B cells up to Month 12. In conclusion, HI immune responses persisted up to 12 mo after vaccination with one-dose and two-dose regimens of the AS03-adjuvanted 3.75 µg HA H1N1 2009 pandemic influenza vaccine, although not all three CHMP guidance criteria for both groups were met at Month 6 and Month 12. The CD4+ T cell and B cell responses also persisted up to Month 12.

  3. Globular Head-Displayed Conserved Influenza H1 Hemagglutinin Stalk Epitopes Confer Protection against Heterologous H1N1 Virus.

    PubMed

    Klausberger, Miriam; Tscheliessnig, Rupert; Neff, Silke; Nachbagauer, Raffael; Wohlbold, Teddy John; Wilde, Monika; Palmberger, Dieter; Krammer, Florian; Jungbauer, Alois; Grabherr, Reingard

    2016-01-01

    Significant genetic variability in the head region of the influenza A hemagglutinin, the main target of current vaccines, makes it challenging to develop a long-lived seasonal influenza prophylaxis. Vaccines based on the conserved hemagglutinin stalk domain might provide broader cross-reactive immunity. However, this region of the hemagglutinin is immunosubdominant to the head region. Peptide-based vaccines have gained much interest as they allow the immune system to focus on relevant but less immunogenic epitopes. We developed a novel influenza A hemagglutinin-based display platform for H1 hemagglutinin stalk peptides that we identified in an epitope mapping assay using human immune sera and synthetic HA peptides. Flow cytometry and competition assays suggest that the identified stalk sequences do not recapitulate the epitopes of already described broadly neutralizing stalk antibodies. Vaccine constructs displaying 25-mer stalk sequences provided up to 75% protection from lethal heterologous virus challenge in BALB/c mice and induced antibody responses against the H1 hemagglutinin. The developed platform based on a vaccine antigen has the potential to be either used as stand-alone or as prime-vaccine in combination with conventional seasonal or pandemic vaccines for the amplification of stalk-based cross-reactive immunity in humans or as platform to evaluate the relevance of viral peptides/epitopes for protection against influenza virus infection.

  4. Causality Assessment of Serious Neurologic Adverse Events Following 2009 H1N1 Vaccination

    PubMed Central

    Williams, S Elizabeth; Pahud, Barbara A; Vellozzi, Claudia; Donofrio, Peter D; Dekker, Cornelia L; Halsey, Neal; Klein, Nicola P; Baxter, Roger P; Marchant, Colin D; LaRussa, Philip S; Barnett, Elizabeth D; Tokars, Jerome I; McGeeney, Brian E; Sparks, Robert C; Aukes, Laurie L.; Jakob, Kathleen; Coronel, Silvia; Sejvar, James J; Slade, Barbara A; Edwards, Kathryn M

    2016-01-01

    Background Adverse events occurring after vaccination are routinely reported to the Vaccine Adverse Event Reporting System (VAERS). We studied serious adverse events (SAEs) of a neurologic nature reported after receipt of influenza A (H1N1) 2009 monovalent vaccine during the 2009–10 influenza season. Investigators in the Clinical Immunization Safety Assessment (CISA) Network sought to characterize these SAEs and to assess their possible causal relationship to vaccination. Methods Centers for Disease Control and Prevention (CDC) and Food and Drug Administration (FDA) physicians reviewed all SAE reports (as defined by the Code of Federal Regulations, 21CFR§314.80) after receipt of H1N1 vaccine reported to VAERS between October 1st 2009 and March 31st 2010. Non-fatal SAE reports with neurologic presentation were referred to CISA investigators, who requested and reviewed additional medical records and clinical information as available. CISA investigators assessed the causal relationship between vaccination and the event using modified WHO criteria as defined. Results 212 VAERS reports of non-fatal serious neurological events were referred for CISA review. Case reports were equally distributed by gender (50.9% female) with an age range of 6 months to 83 years (median 38 years). The most frequent diagnoses reviewed were: Guillain-Barré Syndrome (37.3%), seizures (10.8%), cranial neuropathy (5.7%), and acute disseminated encephalomyelitis (3.8%). Causality assessment resulted in classification of 72 events as “possibly” related (33%), 108 as “unlikely” related (51%), and 20 as “unrelated” (9%) to H1N1 vaccination; none were classified as “probable” or “definite” and 12 were unclassifiable (6%). Conclusion The absence of a specific test to indicate whether a vaccine component contributes to the pathogenesis of an event occurring within a biologically plausible time period makes assessing causality difficult. The development of standardized protocols

  5. Evaluation of a vectored equine herpesvirus type 1 (EHV-1) vaccine expressing H3 haemagglutinin in the protection of dogs against canine influenza.

    PubMed

    Rosas, Cristina; Van de Walle, Gerlinde R; Metzger, Stephan M; Hoelzer, Karin; Dubovi, Edward J; Kim, Sung G; Parrish, Colin R; Osterrieder, Nikolaus

    2008-05-02

    In 2004, canine influenza virus (CIV) was identified as a respiratory pathogen of dogs for the first time and found to be closely related to H3N8 equine influenza virus (EIV). We generated a recombinant vectored vaccine that expresses H3 of a recent isolate of EIV using equine herpesvirus type 1 (EHV-1) as the delivery vehicle. This EHV-1 vectored vaccine exhibited robust and stable EIV H3 expression and induced a strong influenza virus-specific response in both mice and dogs upon intranasal or subcutaneous administration. Furthermore, upon challenge with the recent CIV isolate A/canine/PA/10915-07, protection of vaccinated dogs could be demonstrated by a significant reduction in clinical sings, and, more importantly, by a significant reduction in virus shedding. We concluded that the EHV-1/H3 recombinant vector can be a valuable alternative for protection of dogs against clinical disease induced by CIV and can significantly reduce virus spread.

  6. Evaluation of a vectored equine herpesvirus type 1 (EHV-1) vaccine expressing H3 haemagglutinin in the protection of dogs against canine influenza

    PubMed Central

    Rosas, Cristina; Van de Walle, Gerlinde R.; Metzger, Stephan M.; Hoelzer, Karin; Dubovi, Edward J.; Kim, Sung G.; Parrish, Colin R.; Osterrieder, Nikolaus

    2008-01-01

    In 2004, canine influenza virus (CIV) was identified as a respiratory pathogen of dogs for the first time and is closely related to H3N8 equine influenza virus (EIV). We generated a recombinant vectored vaccine that expresses H3 of a recent isolate of EIV using equine herpesvirus type 1 (EHV-1) as the delivery vehicle. This EHV-1 vectored vaccine exhibited robust and stable EIV H3 expression and induced a strong influenza virus-specific response in both mice and dogs upon intranasal or subcutaneous administration. Furthermore, upon challenge with the recent CIV isolate A/canine/PA/10915-07, protection of vaccinated dogs could be demonstrated by a significant reduction in clinical sings, and, more importantly, by a significant reduction in virus shedding. We concluded that the EHV-1/H3 recombinant vector can be a valuable alternative for protection of dogs against clinical disease induced by CIV and can significantly reduce spread. PMID:18407383

  7. Survey of healthcare workers' attitudes, beliefs and willingness to receive the 2009 pandemic influenza A (H1N1) vaccine and the impact of educational campaigns.

    PubMed

    Thoon, Koh Cheng; Chong, Chia Yin

    2010-04-01

    Vaccination against the 2009 pandemic influenza A (H1N1) represents the best method of controlling spread, morbidity and mortality due to the pandemic. While this has been recommended for all healthcare-workers locally, it is unclear if they are willing to accept the vaccination. A cross-sectional survey was conducted before and after an educational talk on pandemic influenza and vaccines to ascertain responses and stated reasons, as well as identify associated factors. For 235 returned forms prior to the talk, 182 (77.4%) responded positively, while 161 of 192 (83.8%) who returned forms after the talk responded positively. Importantly, 12 of 47 (25.5%) initially negative responses turned positive after education. The desire to protect family, self and patients were the 3 most important reasons for staff wanting to receive the vaccine, while the concern regarding potential side effects was the most important reason for refusal. A high rate of willingness to receive pandemic influenza vaccine was found, which was in contrast to acceptance rates elsewhere and during previous influenza seasons. Education can play an important role in altering vaccine acceptance behaviour, with an emphasis on addressing concerns with regard to potential side effects.

  8. The microRNA-let-7b-mediated attenuated strain of influenza A (H1N1) virus in a mouse model.

    PubMed

    Tan, Mingming; Sun, Wenkui; Feng, Chunlai; Xia, Di; Shen, Xiaoyue; Ding, Yuan; Liu, Zhicheng; Xing, Zheng; Su, Xin; Shi, Yi

    2016-09-30

    Evaluating the attenuation of influenza viruses in animal studies is important in developing safe and effective vaccines. This study aimed to demonstrate that the microRNA (miRNA)-let-7b-mediated attenuated influenza viruses (miRT-H1N1) are sufficiently attenuated and safe in mice. The pathogenicity of the miRT-H1N1virus was investigated in a mouse model, evaluated with median lethal dose (LD50). The replicative dynamics of the miRT-H1N1, wild type (wt)-H1N1, and scramble (scbl)-H1N1 viruses in the lungs of infected mice were compared. The degrees of lesions and the expression levels of IL-6, TNF-α, and IFN-β in the lungs of mice infected with different viruses were also analyzed. In miRT-H1N1 virus-infected mice, 100% of mice survived, and a lower pathogenicity was characterized with non-significant weight loss when compared to mice infected with the control wt virus. The miRT-H1N1 virus was not fatal for mice, even at the highest dose administered. The viral load in the lungs of miRT-H1N1-infected mice was significantly lower than that of the wild-type virus-infected mice. Fewer pulmonary lesions and lower levels of selected pro-inflammatory cytokines in the lungs of the mice infected with the miRT-H1N1 virus were also observed. The virulence of the miRT-H1N1 virus reduced significantly, suggesting that the miRT-H1N1 virus was safe for mice. Our study demonstrated that the miRNA-mediated gene silencing is an alternative approach to attenuating the pathogenicity of wt influenza viruses that have potential in the development of influenza vaccines.

  9. Prevention of influenza virus shedding and protection from lethal H1N1 challenge using a consensus 2009 H1N1 HA and NA adenovirus vector vaccine

    PubMed Central

    Jones, Frank R.; Gabitzsch, Elizabeth S.; Xu, Younong; Balint, Joseph P.; Borisevich, Viktoriya; Smith, Jennifer; Smith, Jeanon; Peng, Bi-Hung; Walker, Aida; Salazar, Magda; Paessler, Slobodan

    2013-01-01

    Vaccines against emerging pathogens such as the 2009 H1N1 pandemic virus can benefit from current technologies such as rapid genomic sequencing to construct the most biologically relevant vaccine. A novel platform (Ad5 [E1-, E2b-]) has been utilized to induce immune responses to various antigenic targets. We employed this vector platform to express hemagglutinin (HA) and neuraminidase (NA) genes from 2009 H1N1 pandemic viruses. Inserts were consensuses sequences designed from viral isolate sequences and the vaccine was rapidly constructed and produced. Vaccination induced H1N1 immune responses in mice, which afforded protection from lethal virus challenge. In ferrets, vaccination protected from disease development and significantly reduced viral titers in nasal washes. H1N1 cell mediated immunity as well as antibody induction correlated with the prevention of disease symptoms and reduction of virus replication. The Ad5 [E1-, E2b-] should be evaluated for the rapid development of effective vaccines against infectious diseases. PMID:21821082

  10. Predictors of H1N1 influenza in the emergency department: proposition for a modified H1N1 case definition.

    PubMed

    Flick, H; Drescher, M; Prattes, J; Tovilo, K; Kessler, H H; Vander, K; Seeber, K; Palfner, M; Raggam, R B; Avian, A; Krause, R; Hoenigl, M

    2014-02-01

    Reliable and rapid diagnosis of influenza A H1N1 is essential to initiate appropriate antiviral therapy and preventive measures. We analysed the differences in clinical presentation and laboratory parameters between emergency department patients with PCR-confirmed H1N1 influenza infection (n = 199) and those with PCR-negative influenza-like illness (ILI; n = 252). Cough, wheezing, leucopenia, eosinopenia and a lower C-reactive protein remained significant predictors of H1N1 influenza. Proposed combinations of clinical symptoms with simple laboratory parameters (e.g. reported or measured fever and either cough or leucocytes <8.5 × 10(9) /L) were clearly superior to currently used official ILI case definitions that use clinical criteria alone. © 2013 The Authors Clinical Microbiology and Infection © 2013 European Society of Clinical Microbiology and Infectious Diseases.

  11. Influence of maternal immunity on vaccine efficacy and susceptibility of one day old chicks against Egyptian highly pathogenic avian influenza H5N1.

    PubMed

    Abdelwhab, E M; Grund, Christian; Aly, Mona M; Beer, Martin; Harder, Timm C; Hafez, Hafez M

    2012-02-24

    In Egypt, continuous circulation of highly pathogenic avian influenza (HPAI) H5N1 viruses of clade 2.2.1 in vaccinated commercial poultry challenges strenuous control efforts. Here, vaccine-derived maternal AIV H5 specific immunity in one-day old chicks was investigated as a factor of vaccine failure in long-term blanket vaccination campaigns in broiler chickens. H5 seropositive one-day old chicks were derived from breeders repeatedly immunized with a commercial inactivated vaccine based on the Potsdam/H5N2 strain. When challenged using the antigenically related HPAIV strain Italy/98 (H5N2) clinical protection was achieved until at least 10 days post-hatch although virus replication was not fully suppressed. No protection at all was observed against the Egyptian HPAIV strain EGYvar/H5N1 representing a vaccine escape lineage. Other groups of chicks with maternal immunity were vaccinated once at 3 or 14 days of age using either the Potsdam/H5N2 vaccine or a vaccine based on EGYvar/H5N1. At day 35 of age these chicks were challenged with the Egyptian HPAIV strain EGYcls/H5N1 which co-circulates with EGYvar/H5N1 but does not represent an antigenic drift variant. The Potsdam/H5N2 vaccinated groups were not protected against EGYcls/H5N1 infection while, in contrast, the EGYvar/H5N1 vaccinated chicks withstand challenge with EGYvar/H5N1 infection. In addition, the results showed that maternal antibodies could interfere with the immune response when a homologous vaccine strain was used. Copyright © 2011. Published by Elsevier B.V.

  12. Potential antigenic explanation for atypical H1N1 infections among middle-aged adults during the 2013-2014 influenza season.

    PubMed

    Linderman, Susanne L; Chambers, Benjamin S; Zost, Seth J; Parkhouse, Kaela; Li, Yang; Herrmann, Christin; Ellebedy, Ali H; Carter, Donald M; Andrews, Sarah F; Zheng, Nai-Ying; Huang, Min; Huang, Yunping; Strauss, Donna; Shaz, Beth H; Hodinka, Richard L; Reyes-Terán, Gustavo; Ross, Ted M; Wilson, Patrick C; Ahmed, Rafi; Bloom, Jesse D; Hensley, Scott E

    2014-11-04

    Influenza viruses typically cause the most severe disease in children and elderly individuals. However, H1N1 viruses disproportionately affected middle-aged adults during the 2013-2014 influenza season. Although H1N1 viruses recently acquired several mutations in the hemagglutinin (HA) glycoprotein, classic serological tests used by surveillance laboratories indicate that these mutations do not change antigenic properties of the virus. Here, we show that one of these mutations is located in a region of HA targeted by antibodies elicited in many middle-aged adults. We find that over 42% of individuals born between 1965 and 1979 possess antibodies that recognize this region of HA. Our findings offer a possible antigenic explanation of why middle-aged adults were highly susceptible to H1N1 viruses during the 2013-2014 influenza season. Our data further suggest that a drifted H1N1 strain should be included in future influenza vaccines to potentially reduce morbidity and mortality in this age group.

  13. A computationally optimized broadly reactive H5 hemagglutinin vaccine provides protection against homologous and heterologous H5N1 highly pathogenic avian influenza virus infection in chickens

    USDA-ARS?s Scientific Manuscript database

    Since its emergence in 1996 in China, H5N1 highly pathogenic avian influenza (HPAI) virus has continuously evolved into different genetic clades that have created challenges to maintaining antigenically relevant H5N1 vaccine seeds. Therefore, a universal (multi-hemagglutinin [HA] subtype) or more c...

  14. Too scared or too capable? Why do college students stay away from the H1N1 vaccine?

    PubMed

    Yang, Z Janet

    2012-10-01

    Although college students were among the populations that had the highest frequency of infection for H1N1 influenza, only 8% of them received H1N1 vaccine this past flu season nationwide. During the peak of this pandemic, information about H1N1 vaccine was widely available. However, knowledge test and behavioral data indicated that most college students were not equipped with basic facts about H1N1 and the H1N1 vaccine. To investigate socio-psychological factors that might have deterred this high-risk population from learning about and getting the H1N1 vaccine, this study tested the utility of a risk information seeking model in addressing this health communication problem. Data collected from an online survey of 371 college students showed that respondents seemed to overestimate how much they knew about the vaccine. Risk information seeking, however, positively influenced their intentions to get the vaccine. Results suggested that to communicate effectively to this population, it is important to emphasize the difference between perceived knowledge and actual knowledge, monitor emotional responses to potential risks, and promote getting flu vaccination as a socially desirable behavior. © 2012 Society for Risk Analysis.

  15. Co-circulation of pandemic 2009 H1N1, classical swine H1N1 and avian-like swine H1N1 influenza viruses in pigs in China.

    PubMed

    Chen, Yan; Zhang, Jian; Qiao, Chuanling; Yang, Huanliang; Zhang, Ying; Xin, Xiaoguang; Chen, Hualan

    2013-01-01

    The pandemic A/H1N1 influenza viruses emerged in both Mexico and the United States in March 2009, and were transmitted efficiently in the human population. They were transmitted occasionally from humans to other mammals including pigs, dogs and cats. In this study, we report the isolation and genetic analysis of novel viruses in pigs in China. These viruses were related phylogenetically to the pandemic 2009 H1N1 influenza viruses isolated from humans and pigs, which indicates that the pandemic virus is currently circulating in swine populations, and this hypothesis was further supported by serological surveillance of pig sera collected within the same period. Furthermore, we isolated another two H1N1 viruses belonging to the lineages of classical swine H1N1 virus and avian-like swine H1N1 virus, respectively. Multiple genetic lineages of H1N1 viruses are co-circulating in the swine population, which highlights the importance of intensive surveillance for swine influenza in China. Copyright © 2012 Elsevier B.V. All rights reserved.

  16. Factors influencing H1N1 vaccine behavior among Manitoba Metis in Canada: a qualitative study.

    PubMed

    Driedger, S Michelle; Maier, Ryan; Furgal, Chris; Jardine, Cindy

    2015-02-12

    During the first wave of the H1N1 influenza pandemic in 2009, Aboriginal populations in Canada experienced disproportionate rates of infection, particularly in the province of Manitoba. To protect those thought to be most at-risk, health authorities in Manitoba listed all Aboriginal people, including Metis, among those able to receive priority access to the novel vaccine when it first became available. Currently, no studies exist that have investigated the attitudes, influences, and vaccine behaviors among Aboriginal communities in Canada. This paper is the first to systematically connect vaccine behavior with the attitudes and beliefs that influenced Metis study participants' H1N1 vaccine decision-making. Researchers held focus groups (n = 17) with Metis participants in urban, rural, and remote locations of Manitoba following the conclusion of the H1N1 pandemic. Participants were asked about their vaccination decisions and about the factors that influenced their decisions. Following data collection, responses were coded into the broad categories of a social-ecological model, nuanced by categories stemming from earlier research. Responses were then quantified to show the most influential factors in positively or negatively affecting the vaccine decision. Media reporting, the influence of peer groups, and prioritization all had positive and negative influential effects on decision making. Whether vaccinated or not, the most negatively influential factors cited by participants were a lack of knowledge about the vaccine and the pandemic as well as concerns about vaccine safety. Risk of contracting H1N1 influenza was the biggest factor in positively influencing a vaccine decision, which in many cases trumped any co-existing negative influencers. Metis experiences of colonialism in Canada deeply affected their perceptions of the vaccine and pandemic, a context that health systems need to take into account when planning response activities in the future. Participants

  17. Efficacy of a Recombinant Turkey Herpesvirus H5 Vaccine Against Challenge With H5N1 Clades 1.1.2 and 2.3.2.1 Highly Pathogenic Avian Influenza Viruses in Domestic Ducks (Anas platyrhynchos domesticus).

    PubMed

    Pantin-Jackwood, Mary J; Kapczynski, Darrell R; DeJesus, Eric; Costa-Hurtado, Mar; Dauphin, Gwenaelle; Tripodi, Astrid; Dunn, John R; Swayne, David E

    2016-03-01

    Domestic ducks are the second most abundant poultry species in many Asian countries and have played a critical role in the epizootiology of H5N1 highly pathogenic avian influenza (HPAI).In this study, the protective efficacy of a live recombinant vector vaccine based on a turkey herpesvirus (HVT) expressing the H5 gene from a clade 2.2 H5N1 HPAI strain (A/Swan/Hungary/4999/ 2006) (rHVT-H5/2.2), given at 3 days of age, was examined in Pekin ducks (Anas platyrhynchos domesticus). The vaccine was given alone or in combination with an inactivated H5N1 clade 2.3.2.1 reverse genetic (rgGD/2.3.2.1) vaccine given at 16 days of age, either as a single vaccination or in a prime-boost regime. At 30 days of age, ducks were challenged with one of two H5N1 HPAI viruses: A/duck/Vietnam/NCVD-2721/2013 (clade 1.1.2) or A/duck/Vietnam/NCVD-1584/2012 (clade 2.3.2.1.C). These viruses produced 100% mortality in less than 5 days in nonvaccinated control ducks. Ducks vaccinated with the rgGD/2.3.2.1 vaccine, with or without the rHVT-H5/2.2 vaccine, were 90%-100% protected against mortality after challenge with either of the two H5N1 HPAI viruses. The rHVT-H5/2.2 vaccine alone, however, conferred only 30% protection against mortality after challenge with either H5N1 HPAI virus; the surviving ducks from these groups shed higher amount of virus and for longer than the single-vaccinated rgGD/2.3.2.1 group. Despite low protection, ducks vaccinated with the rHVT-H5/2.2 vaccine and challenged with the clade 1.1.2 Vietnam virus had a longer mean death time than nonvaccinated controls (P = 0.02). A booster effect was found on reduction of virus shedding when using both vaccines, with lower oropharyngeal viral titers at 4 days after challenge with either HPAI virus (P < 0.05). Neither rHVT-H5/2.2 nor standard HVT vaccine could be detected in samples collected from multiple tissues at different time points, indicting minimal levels of viral replication. In conclusion, although a minor effect on

  18. Narcolepsy with cataplexy and hyperthyroidism sudden appeared after H1N1 vaccination

    PubMed Central

    Leiva, Silvia; Madrazo, Jimena; Podesta, Claudio

    2018-01-01

    Narcolepsy type 1 (NT1) is a chronic sleep disorder, characterized by excessive daytime sleepiness, cataplexy and fragmented nocturnal sleep. It is caused by a hypocretin deficiency due to a significant reduction of the neurons producing it. In the last years, it has been postulated that an autoimmune mechanism would be responsible for the destruction of these neurons in those genetically predisposed patients. The increased incidence of narcolepsy after the pandemic H1N1 influenza vaccination campaign in 2009-2010 is known. We present below the case of an adult patient who, 10 days after receiving H1N1 vaccination, suffers a traffic accident after falling asleep. Subsequent studies revealed hyperthyroidism due to Graves disease. In spite of the treatment, the patient persisted with daily and disabling daytime sleepiness, sleep attacks and episodes of generalized muscle atony with preservation of consciousness. A nocturnal polysomnography and multiple sleep latency test (MSLT) were performed with a diagnosis of NT1. The particularity of this case is the presentation of 2 autoimmune diseases triggered by an H1N1 vaccine without adjuvant, so far there is only evidence of NT1 associated with vaccines with adjuvant and viral infection. The association of both entities has made us reflect on the autoimmune mechanism, reinforcing the theory of its role in the onset of the disease. PMID:29796199

  19. Safety and Immunogenicity of 2009 pH1N1 Vaccination in HIV-Infected Pregnant Women

    PubMed Central

    Abzug, Mark J.; Nachman, Sharon A.; Muresan, Petronella; Handelsman, Edward; Watts, D. Heather; Fenton, Terence; Heckman, Barbara; Petzold, Elizabeth; Weinberg, Adriana; Levin, Myron J.; Siberry, George; Miller, Judi; Levy, Wende; Heckman, Barbara; Ebiasah, Ruth; Palumbo, Paul; Dragavon, Joan; Donelson, Lori; Jurgrau, Andrea; Garry, David; Bloom, Anthony

    2013-01-01

    Background. Pregnant women infected with human immunodeficiency virus (HIV) may have particular vulnerability to 2009 pandemic H1N1 influenza (pH1N1) infection. The safety and immunogenicity of pH1N1 vaccination in HIV-infected pregnant women are unknown. Methods. HIV-infected women 18–39 years of age and 14–34 weeks’ gestation on antiretroviral therapy received two 30-μg doses of unadjuvanted, inactivated pH1N1 vaccine 21 days apart. Hemagglutination inhibition titers were measured at entry, 21 days after dose 1, and 10 and 21 days after dose 2, and, in mothers and infants, at delivery and 3 and 6 months postdelivery. Results. No severe vaccine-related adverse events were observed among 127 subjects. At entry, 21% had seroprotective (≥1:40) titers. Seroprotection and seroresponse (≥4-fold rise) occurred in 73% and 66% after dose 1 and 80% and 72% after dose 2, respectively. Of women lacking seroprotection at entry, 66% attained seroprotection after dose 1 and 75% after dose 2. Seroprotective titers were present in 67% of mothers and 65% of infants at delivery (median 66 days after dose 2), 60% of mothers and 26% of infants at 3 months postdelivery, and 59% of mothers and 12% of infants at 6 months postdelivery. Conclusions. Two 30-μg doses were moderately immunogenic in HIV-infected pregnant women. No concerning vaccine-related safety signals were observed. Seroprotection persisted in most women postpartum. Efficient transplacental antibody transfer occurred, but seroprotection in infants waned rapidly. Vaccination to protect HIV-infected pregnant women and their newborns from new influenza strains is feasible, but more immunogenic platforms should be evaluated. Clinical Trials Registration. NCT00992017. PMID:23378284

  20. Outbreaks of pandemic (H1N1) 2009 and seasonal influenza A (H3N2) on cruise ship.

    PubMed

    Ward, Kate A; Armstrong, Paul; McAnulty, Jeremy M; Iwasenko, Jenna M; Dwyer, Dominic E

    2010-11-01

    To determine the extent and pattern of influenza transmission and effectiveness of containment measures, we investigated dual outbreaks of pandemic (H1N1) 2009 and influenza A (H3N2) that had occurred on a cruise ship in May 2009. Of 1,970 passengers and 734 crew members, 82 (3.0%) were infected with pandemic (H1N1) 2009 virus, 98 (3.6%) with influenza A (H3N2) virus, and 2 (0.1%) with both. Among 45 children who visited the ship's childcare center, infection rate for pandemic (H1N1) 2009 was higher than that for influenza A (H3N2) viruses. Disembarked passengers reported a high level of compliance with isolation and quarantine recommendations. We found 4 subsequent cases epidemiologically linked to passengers but no evidence of sustained transmission to the community or passengers on the next cruise. Among this population of generally healthy passengers, children seemed more susceptible to pandemic (H1N1) 2009 than to influenza (H3N2) viruses. Intensive disease control measures successfully contained these outbreaks.

  1. Immunogenicity and Safety of Varying Dosages of a Monovalent 2009 H1N1 Influenza Vaccine Given With and Without AS03 Adjuvant System in Healthy Adults and Older Persons

    PubMed Central

    Jackson, Lisa A.; Chen, Wilbur H.; Stapleton, Jack T.; Dekker, Cornelia L.; Wald, Anna; Brady, Rebecca C.; Edupuganti, Srilatha; Winokur, Patricia; Mulligan, Mark J.; Keyserling, Harry L.; Kotloff, Karen L.; Rouphael, Nadine; Noah, Diana L.; Hill, Heather; Wolff, Mark C.

    2012-01-01

    Background. Adjuvanted vaccines have the potential to improve influenza pandemic response. AS03 adjuvant has been shown to enhance the immune response to inactivated influenza vaccines. Methods. This trial was designed to evaluate the immunogenicity and safety of an inactivated 2009 H1N1 influenza vaccine at varying dosages of hemagglutinin with and without extemporaneously mixed AS03 adjuvant system in adults ≥18 years of age. Adults were randomized to receive 2 doses of 1 of 5 vaccine formulations (3.75 µg, 7.5 µg, or 15 µg with AS03 or 7.5 µg or 15 µg without adjuvant). Results. The study population included 544 persons <65 years of age and 245 persons ≥65 years of age. Local adverse events tended to be more frequent in the adjuvanted vaccine groups, but severe reactions were uncommon. In both age groups, hemagglutination inhibition antibody geometric mean titers after dose one were higher in the adjuvanted groups, compared with the 15 µg unadjuvanted group, and this difference was statistically significant for the comparison of the 15 µg adjuvanted group with the 15 µg unadjuvanted group. Conclusions. AS03 adjuvant system improves the immune response to inactivated 2009 H1N1 influenza vaccine in both younger and older adults and is generally well tolerated. ClinicalTrials.gov NCT00963157 PMID:22782949

  2. Antigenic Drift of the Pandemic 2009 A(H1N1) Influenza Virus in a Ferret Model

    PubMed Central

    Guarnaccia, Teagan; Carolan, Louise A.; Maurer-Stroh, Sebastian; Lee, Raphael T. C.; Job, Emma; Reading, Patrick C.; Petrie, Stephen; McCaw, James M.; McVernon, Jodie; Hurt, Aeron C.; Kelso, Anne; Mosse, Jennifer; Barr, Ian G.; Laurie, Karen L.

    2013-01-01

    Surveillance data indicate that most circulating A(H1N1)pdm09 influenza viruses have remained antigenically similar since they emerged in humans in 2009. However, antigenic drift is likely to occur in the future in response to increasing population immunity induced by infection or vaccination. In this study, sequential passaging of A(H1N1)pdm09 virus by contact transmission through two independent series of suboptimally vaccinated ferrets resulted in selection of variant viruses with an amino acid substitution (N156K, H1 numbering without signal peptide; N159K, H3 numbering without signal peptide; N173K, H1 numbering from first methionine) in a known antigenic site of the viral HA. The N156K HA variant replicated and transmitted efficiently between naïve ferrets and outgrew wildtype virus in vivo in ferrets in the presence and absence of immune pressure. In vitro, in a range of cell culture systems, the N156K variant rapidly adapted, acquiring additional mutations in the viral HA that also potentially affected antigenic properties. The N156K escape mutant was antigenically distinct from wildtype virus as shown by binding of HA-specific antibodies. Glycan binding assays demonstrated the N156K escape mutant had altered receptor binding preferences compared to wildtype virus, which was supported by computational modeling predictions. The N156K substitution, and culture adaptations, have been detected in human A(H1N1)pdm09 viruses with N156K preferentially reported in sequences from original clinical samples rather than cultured isolates. This study demonstrates the ability of the A(H1N1)pdm09 virus to undergo rapid antigenic change to evade a low level vaccine response, while remaining fit in a ferret transmission model of immunization and infection. Furthermore, the potential changes in receptor binding properties that accompany antigenic changes highlight the importance of routine characterization of clinical samples in human A(H1N1)pdm09 influenza surveillance

  3. Evaluation of the attenuation, immunogenicity, and efficacy of a live virus vaccine generated by codon-pair bias de-optimization of the 2009 pandemic H1N1 influenza virus, in ferrets

    PubMed Central

    Broadbent, Andrew J.; Santos, Celia P.; Anafu, Amanda; Wimmer, Eckard; Mueller, Steffen; Subbarao, Kanta

    2015-01-01

    Codon-pair bias de-optimization (CPBD) of viruses involves re-writing viral genes using statistically underrepresented codon pairs, without any changes to the amino acid sequence or codon usage. Previously, this technology has been used to attenuate the influenza A/Puerto Rico/8/34 (H1N1) virus. The de-optimized virus was immunogenic and protected inbred mice from challenge. In order to assess whether CPBD could be used to produce a live vaccine against a clinically relevant influenza virus, we generated an influenza A/California/07/2009 pandemic H1N1 (2009 pH1N1) virus with de-optimized HA and NA gene segments (2009 pH1N1-(HA+NA)Min), and evaluated viral replication and protein expression in MDCK cells, and attenuation, immunogenicity, and efficacy in outbred ferrets. The 2009 pH1N1-(HA+NA)Min virus grew to a similar titer as the 2009 pH1N1 wild type (wt) virus in MDCK cells (~106 TCID50/ml), despite reduced HA and NA protein expression on western blot. In ferrets, intranasal inoculation of 2009 pH1N1-(HA+NA)Min virus at doses ranging from 103 to 105 TCID50 led to seroconversion in all animals and protection from challenge with the 2009 pH1N1 wt virus 28 days later. The 2009 pH1N1-(HA+NA)Min virus did not cause clinical illness in ferrets, but replicated to a similar titer as the wt virus in the upper and lower respiratory tract, suggesting that de-optimization of additional gene segments may be warranted for improved attenuation. Taken together, our data demonstrate the potential of using CPBD technology for the development of a live influenza virus vaccine if the level of attenuation is optimized. PMID:26655630

  4. Infection of mice with a human influenza A/H3N2 virus induces protective immunity against lethal infection with influenza A/H5N1 virus.

    PubMed

    Kreijtz, J H C M; Bodewes, R; van den Brand, J M A; de Mutsert, G; Baas, C; van Amerongen, G; Fouchier, R A M; Osterhaus, A D M E; Rimmelzwaan, G F

    2009-08-06

    The transmission of highly pathogenic avian influenza (HPAI) A viruses of the H5N1 subtype from poultry to man and the high case fatality rate fuels the fear for a pandemic outbreak caused by these viruses. However, prior infections with seasonal influenza A/H1N1 and A/H3N2 viruses induce heterosubtypic immunity that could afford a certain degree of protection against infection with the HPAI A/H5N1 viruses, which are distantly related to the human influenza A viruses. To assess the protective efficacy of such heterosubtypic immunity mice were infected with human influenza virus A/Hong Kong/2/68 (H3N2) 4 weeks prior to a lethal infection with HPAI virus A/Indonesia/5/05 (H5N1). Prior infection with influenza virus A/Hong Kong/2/68 reduced clinical signs, body weight loss, mortality and virus replication in the lungs as compared to naive mice infected with HPAI virus A/Indonesia/5/05. Priming by infection with respiratory syncytial virus, a non-related virus did not have a beneficial effect on the outcome of A/H5N1 infections, indicating that adaptive immune responses were responsible for the protective effect. In mice primed by infection with influenza A/H3N2 virus cytotoxic T lymphocytes (CTL) specific for NP(366-374) epitope ASNENMDAM and PA(224-232) SCLENFRAYV were observed. A small proportion of these CTL was cross-reactive with the peptide variant derived from the influenza A/H5N1 virus (ASNENMEVM and SSLENFRAYV respectively) and upon challenge infection with the influenza A/H5N1 virus cross-reactive CTL were selectively expanded. These CTL, in addition to those directed to conserved epitopes, shared by the influenza A/H3N2 and A/H5N1 viruses, most likely contributed to accelerated clearance of the influenza A/H5N1 virus infection. Although also other arms of the adaptive immune response may contribute to heterosubtypic immunity, the induction of virus-specific CTL may be an attractive target for development of broad protective vaccines. Furthermore the

  5. Enhanced genetic characterization of influenza A(H3N2) viruses and vaccine effectiveness by genetic group, 2014–2015

    PubMed Central

    Flannery, Brendan; Zimmerman, Richard K.; Gubareva, Larisa V.; Garten, Rebecca J.; Chung, Jessie R.; Nowalk, Mary Patricia; Jackson, Michael L.; Jackson, Lisa A.; Monto, Arnold S.; Ohmit, Suzanne E.; Belongia, Edward A.; McLean, Huong Q.; Gaglani, Manjusha; Piedra, Pedro A.; Mishin, Vasiliy P.; Chesnokov, Anton P.; Spencer, Sarah; Thaker, Swathi N.; Barnes, John R.; Foust, Angie; Sessions, Wendy; Xu, Xiyan; Katz, Jacqueline; Fry, Alicia M.

    2018-01-01

    Background During the 2014–15 US influenza season, expanded genetic characterization of circulating influenza A(H3N2) viruses was used to assess the impact of genetic variability of influenza A(H3N2) viruses on influenza vaccine effectiveness (VE). Methods A novel pyrosequencing assay was used to determine genetic group based on hemagglutinin (HA) gene sequences of influenza A(H3N2) viruses from patients enrolled US Flu Vaccine Effectiveness network sites. Vaccine effectiveness was estimated using a test-negative design comparing vaccination among patients infected with influenza A(H3N2) viruses and uninfected patients. Results Among 9710 enrollees, 1868 (19%) tested positive for influenza A(H3N2); genetic characterization of 1397 viruses showed 1134 (81%) belonged to one HA genetic group (3C.2a) of antigenically drifted H3N2 viruses. Effectiveness of 2014–15 influenza vaccination varied by A(H3N2) genetic group from 1% (95% confidence interval [CI], −14% to 14%) against illness caused by antigenically drifted A(H3N2) group 3C.2a viruses versus 44% (95% CI, 16% to 63%) against illness caused by vaccine-like A(H3N2) group 3C.3b viruses. Conclusion Effectiveness of 2014–15 influenza vaccination varied by genetic group of influenza A(H3N2) virus. Changes in hemagglutinin genes related to antigenic drift were associated with reduced vaccine effectiveness. PMID:27190176

  6. Fulminant fatal swine influenza (H1N1): Myocarditis, myocardial infarction, or severe influenza pneumonia?

    PubMed

    Cunha, Burke A; Syed, Uzma; Mickail, Nardeen

    2010-01-01

    The swine influenza (H1N1) pandemic began in Mexico and rapidly spread worldwide. As is the case with pandemic influenza A, the majority of early deaths have been in young healthy adults. The complications of pandemic H1N1 have been reported from several centers. Noteworthy has been the relative rarity of bacterial coinfection in bacterial pneumonia in hospitalized adults with H1N1 pneumonia. Simultaneous bacterial community-acquired pneumonia due to methicillin-sensitive Staphylococcus aureus or community-acquired methicillin resistant S. aureus and subsequent bacterial community-acquired pneumonia due to S. pneumoniae or Haemophilus influenzae have been reportedly rare (0.4%-4% of well-documented cases). Cardiac complications of H1N1 infection have been uncommon. Young healthy adults without a cardiac history who have H1N1 and chest pain usually have either acute myocardial infarction or acute myocarditis. Cardiac symptomatology with H1N1 often overshadows pulmonary manifestations, that is, influenza pneumonia. With H1N1 pneumonia, clinicians should be alert for otherwise unexplained tachycardia or chest pain that may represent acute myocardial infarction or myocarditis. We present a case of rapidly fatal H1N1 in a young adult treated with oseltamivir and peramivir. He was initially tachycardic, thought to represent myocarditis. He subsequently became hypotensive and expired. At autopsy there was cardiomegaly present but there were no signs of acute myocardial infarction or myocarditis. Pathologically, he died of severe H1N1 pneumonia and not bacterial pneumonia. Copyright © 2010 Elsevier Inc. All rights reserved.

  7. Detection of influenza A(H1N1)v virus by real-time RT-PCR.

    PubMed

    Panning, M; Eickmann, M; Landt, O; Monazahian, M; Olschläger, S; Baumgarte, S; Reischl, U; Wenzel, J J; Niller, H H; Günther, S; Hollmann, B; Huzly, D; Drexler, J F; Helmer, A; Becker, S; Matz, B; Eis-Hübinger, Am; Drosten, C

    2009-09-10

    Influenza A(H1N1)v virus was first identified in April 2009. A novel real-time RT-PCR for influenza A(H1N1)v virus was set up ad hoc and validated following industry-standard criteria. The lower limit of detection of the assay was 384 copies of viral RNA per ml of viral transport medium (95% confidence interval: 273-876 RNA copies/ml). Specificity was 100% as assessed on a panel of reference samples including seasonal human influenza A virus H1N1 and H3N2, highly pathogenic avian influenza A virus H5N1 and porcine influenza A virus H1N1, H1N2 and H3N2 samples. The real-time RT-PCR assay for the influenza A matrix gene recommended in 2007 by the World Health Organization was modified to work under the same reaction conditions as the influenza A(H1N1)v virus-specific test. Both assays were equally sensitive. Clinical applicability of both assays was demonstrated by screening of almost 2,000 suspected influenza (H1N1)v specimens, which included samples from the first cases of pandemic H1N1 influenza imported to Germany. Measuring influenza A(H1N1)v virus concentrations in 144 laboratory-confirmed samples yielded a median of 4.6 log RNA copies/ml. The new methodology proved its principle and might assist public health laboratories in the upcoming influenza pandemic.

  8. North American triple reassortant and Eurasian H1N1 swine influenza viruses do not readily reassort to generate a 2009 pandemic H1N1-like virus.

    PubMed

    Ma, Wenjun; Liu, Qinfang; Qiao, Chuanling; del Real, Gustavo; García-Sastre, Adolfo; Webby, Richard J; Richt, Jürgen A

    2014-03-11

    The 2009 pandemic H1N1 virus (pH1N1) was derived through reassortment of North American triple reassortant and Eurasian avian-like swine influenza viruses (SIVs). To date, when, how and where the pH1N1 arose is not understood. To investigate viral reassortment, we coinfected cell cultures and a group of pigs with or without preexisting immunity with a Eurasian H1N1 virus, A/Swine/Spain/53207/2004 (SP04), and a North American triple reassortant H1N1 virus, A/Swine/Kansas/77778/2007 (KS07). The infected pigs were cohoused with one or two groups of contact animals to investigate viral transmission. In coinfected MDCK or PK15 continuous cell lines with KS07 and SP04 viruses, more than 20 different reassortant viruses were found. In pigs without or with preexisting immunity (immunized with commercial inactivated swine influenza vaccines) and coinfected with both viruses, six or seven reassortant viruses, as well as the parental viruses, were identified in bronchoalveolar lavage fluid samples from the lungs. Interestingly, only one or two viruses transmitted to and were detected in contact animals. No reassortant containing a gene constellation similar to that of pH1N1 virus was found in either coinfected cells or pigs, indicating that the reassortment event that resulted in the generation of this virus is a rare event that likely involved specific viral strains and/or a favorable, not-yet-understood environment. IMPORTANCE The 2009 pandemic-like H1N1 virus could not be reproduced either in cell cultures or in pigs coinfected with North American triple reassortant H1N1 and Eurasian H1N1 swine influenza viruses. This finding suggests that the generation of the 2009 pandemic H1N1 virus by reassortment was a rare event that likely involved specific viral strains and unknown factors. Different reassortant viruses were detected in coinfected pigs with and without preexisting immunity, indicating that host immunity plays a relevant role in driving viral reassortment of

  9. Comparison of Shedding Characteristics of Seasonal Influenza Virus (Sub)Types and Influenza A(H1N1)pdm09; Germany, 2007–2011

    PubMed Central

    Suess, Thorsten; Remschmidt, Cornelius; Schink, Susanne B.; Schweiger, Brunhilde; Heider, Alla; Milde, Jeanette; Nitsche, Andreas; Schroeder, Kati; Doellinger, Joerg; Braun, Christian; Haas, Walter; Krause, Gérard; Buchholz, Udo

    2012-01-01

    Background Influenza viral shedding studies provide fundamental information for preventive strategies and modelling exercises. We conducted a prospective household study to investigate viral shedding in seasonal and pandemic influenza between 2007 and 2011 in Berlin and Munich, Germany. Methods Study physicians recruited index patients and their household members. Serial nasal specimens were obtained from all household members over at least eight days and tested quantitatively by qRT-PCR for the influenza virus (sub)type of the index patient. A subset of samples was also tested by viral culture. Symptoms were recorded daily. Results We recruited 122 index patients and 320 household contacts, of which 67 became secondary household cases. Among all 189 influenza cases, 12 were infected with seasonal/prepandemic influenza A(H1N1), 19 with A(H3N2), 60 with influenza B, and 98 with A(H1N1)pdm09. Nine (14%) of 65 non-vaccinated secondary cases were asymptomatic/subclinical (0 (0%) of 21 children, 9 (21%) of 44 adults; p = 0.03). Viral load among patients with influenza-like illness (ILI) peaked on illness days 1, 2 or 3 for all (sub)types and declined steadily until days 7–9. Clinical symptom scores roughly paralleled viral shedding dynamics. On the first day prior to symptom onset 30% (12/40) of specimens were positive. Viral load in 6 asymptomatic/subclinical patients was similar to that in ILI-patients. Duration of infectiousness as measured by viral culture lasted approximately until illness days 4–6. Viral load did not seem to be influenced by antiviral therapy, age or vaccination status. Conclusion Asymptomatic/subclinical infections occur infrequently, but may be associated with substantial amounts of viral shedding. Presymptomatic shedding may arise in one third of cases, and shedding characteristics appear to be independent of (seasonal or pandemic) (sub)type, age, antiviral therapy or vaccination; however the power to find moderate differences was

  10. Identification of reassortant pandemic H1N1 influenza virus in Korean pigs.

    PubMed

    Han, Jae Yeon; Park, Sung Jun; Kim, Hye Kwon; Rho, Semi; Nguyen, Giap Van; Song, Daesub; Kang, Bo Kyu; Moon, Hyung Jun; Yeom, Min Joo; Park, Bong Kyun

    2012-05-01

    Since the 2009 pandemic human H1N1 influenza A virus emerged in April 2009, novel reassortant strains have been identified throughout the world. This paper describes the detection and isolation of reassortant strains associated with human pandemic influenza H1N1 and swine influenza H1N2 (SIV) viruses in swine populations in South Korea. Two influenza H1N2 reassortants were detected, and subtyped by PCR. The strains were isolated using Madin- Darby canine kidney (MDCK) cells, and genetically characterized by phylogenetic analysis for genetic diversity. They consisted of human, avian, and swine virus genes that were originated from the 2009 pandemic H1N1 virus and a neuraminidase (NA) gene from H1N2 SIV previously isolated in North America. This identification of reassortment events in swine farms raises concern that reassortant strains may continuously circulate within swine populations, calling for the further study and surveillance of pandemic H1N1 among swine.

  11. Serum IgG titres, but not avidity, correlates with neutralizing antibody response after H5N1 vaccination.

    PubMed

    Pedersen, Gabriel Kristian; Höschler, Katja; Øie Solbak, Sara Marie; Bredholt, Geir; Pathirana, Rishi Delan; Afsar, Aram; Breakwell, Lucy; Nøstbakken, Jane Kristin; Raae, Arnt Johan; Brokstad, Karl Albert; Sjursen, Haakon; Zambon, Maria; Cox, Rebecca Jane

    2014-07-31

    Influenza H5N1 virus constitutes a pandemic threat and development of effective H5N1 vaccines is a global priority. Anti-influenza antibodies directed towards the haemagglutinin (HA) define a correlate of protection. Both antibody concentration and avidity may be important for virus neutralization and resolving influenza disease. We conducted a phase I clinical trial of a virosomal H5N1 vaccine adjuvanted with the immunostimulating complex Matrix M™. Sixty adults were intramuscularly immunized with two vaccine doses (21 days apart) of 30 μg HA alone or 1.5, 7.5 or 30 μg HA adjuvanted with Matrix M™. Serum H5 HA1-specific antibodies and virus neutralization were determined at days 0, 21, 42, 180 and 360 and long-term memory B cells at day 360 post-vaccination. The binding of the HA specific antibodies was measured by avidity NaSCN-elution ELISA and surface plasmon resonance (SPR). The H5 HA1-specific IgG response peaked after the second dose (day 42), was dominated by IgG1 and IgG3 and was highest in the adjuvanted vaccine groups. IgG titres correlated significantly with virus neutralization at all time points (Spearman r≥0.66, p<0.0001). By elution ELISA, serum antibody avidity was highest at days 180 and 360 post vaccination and did not correlate with virus neutralization. Long-lasting H5 HA1-specific memory B cells produced high IgG antibody avidity similar to serum IgG. Maturation of serum antibody avidity continued up to day 360 after influenza H5N1 vaccination. Virus neutralization correlated with serum H5 HA1-specific IgG antibody concentrations and not antibody avidity. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. Long-term immunogenicity of two doses of 2009 A/H1N1v vaccine with and without AS03(A) adjuvant in HIV-1-infected adults.

    PubMed

    Durier, Christine; Desaint, Corinne; Lucht, Frédéric; Girard, Pierre-Marie; Lévy, Yves; May, Thierry; Michelet, Christian; Rami, Agathe; Roman, François; Delfraissy, Jean-François; Aboulker, Jean-Pierre; Launay, Odile

    2013-01-02

    In immunocompromised patients, alternative schedules more immunogenic than the standard influenza vaccine regimen are necessary to enhance and prolong vaccine efficacy. We previously reported that the AS03A-adjuvanted 2009 A/H1N1v vaccine yielded a higher short-term immune response than the nonadjuvanted one in HIV-1-infected adults. This study reports the long-term persistence of the immune response. In a prospective, multicenter, randomized, patient-blinded trial, two doses of AS03A-adjuvanted H1N1v vaccine containing 3.75 μg haemagglutinin (n = 155; group A) or nonadjuvanted H1N1v vaccine containing 15 μg haemagglutinin (n = 151; group B), were administered 21 days apart. Haemagglutination inhibition and neutralizing antibodies were assessed 6 and 12 months after vaccination. In group A and B, the seroprotection rates were 83.7 and 59.4% at month 6, and 70.4 and 49.3 at month 12, respectively. In a multivariate analysis, persistence of seroprotection 12 months after vaccination was negatively associated with current smoking (odds ratio = 0.6, P = 0.03) and positively related with the AS03A-adjuvanted H1N1v vaccine (odds ratio = 2.7, P = 0.0002). In HIV-1-infected adults, two doses of adjuvanted influenza vaccine induce long-term persistence of immune response up to 1 year after vaccination.

  13. Rules of co-occurring mutations characterize the antigenic evolution of human influenza A/H3N2, A/H1N1 and B viruses.

    PubMed

    Chen, Haifen; Zhou, Xinrui; Zheng, Jie; Kwoh, Chee-Keong

    2016-12-05

    The human influenza viruses undergo rapid evolution (especially in hemagglutinin (HA), a glycoprotein on the surface of the virus), which enables the virus population to constantly evade the human immune system. Therefore, the vaccine has to be updated every year to stay effective. There is a need to characterize the evolution of influenza viruses for better selection of vaccine candidates and the prediction of pandemic strains. Studies have shown that the influenza hemagglutinin evolution is driven by the simultaneous mutations at antigenic sites. Here, we analyze simultaneous or co-occurring mutations in the HA protein of human influenza A/H3N2, A/H1N1 and B viruses to predict potential mutations, characterizing the antigenic evolution. We obtain the rules of mutation co-occurrence using association rule mining after extracting HA1 sequences and detect co-mutation sites under strong selective pressure. Then we predict the potential drifts with specific mutations of the viruses based on the rules and compare the results with the "observed" mutations in different years. The sites under frequent mutations are in antigenic regions (epitopes) or receptor binding sites. Our study demonstrates the co-occurring site mutations obtained by rule mining can capture the evolution of influenza viruses, and confirms that cooperative interactions among sites of HA1 protein drive the influenza antigenic evolution.

  14. Household Transmission of Influenza A(H1N1)pdm09 in the Pandemic and Post-Pandemic Seasons

    PubMed Central

    Casado, Itziar; Martínez-Baz, Iván; Burgui, Rosana; Irisarri, Fátima; Arriazu, Maite; Elía, Fernando; Navascués, Ana; Ezpeleta, Carmen; Aldaz, Pablo; Castilla, Jesús

    2014-01-01

    Background The transmission of influenza viruses occurs person to person and is facilitated by contacts within enclosed environments such as households. The aim of this study was to evaluate secondary attack rates and factors associated with household transmission of laboratory-confirmed influenza A(H1N1)pdm09 in the pandemic and post-pandemic seasons. Methods During the 2009–2010 and 2010–2011 influenza seasons, 76 sentinel physicians in Navarra, Spain, took nasopharyngeal and pharyngeal swabs from patients diagnosed with influenza-like illness. A trained nurse telephoned households of those patients who were laboratory-confirmed for influenza A(H1N1)pdm09 to ask about the symptoms, risk factors and vaccination status of each household member. Results In the 405 households with a patient laboratory-confirmed for influenza A(H1N1)pdm09, 977 susceptible contacts were identified; 16% of them (95% CI 14–19%) presented influenza-like illness and were considered as secondary cases. The secondary attack rate was 14% in 2009–2010 and 19% in the 2010–2011 season (p = 0.049), an increase that mainly affected persons with major chronic conditions. In the multivariate logistic regression analysis, the risk of being a secondary case was higher in the 2010–2011 season than in the 2009–2010 season (adjusted odds ratio: 1.72; 95% CI 1.17–2.54), and in children under 5 years, with a decreasing risk in older contacts. Influenza vaccination was associated with lesser incidence of influenza-like illness near to statistical significance (adjusted odds ratio: 0.29; 95% CI 0.08–1.03). Conclusion The secondary attack rate in households was higher in the second season than in the first pandemic season. Children had a greater risk of infection. Preventive measures should be maintained in the second pandemic season, especially in high-risk persons. PMID:25254376

  15. Outbreaks of Pandemic (H1N1) 2009 and Seasonal Influenza A (H3N2) on Cruise Ship

    PubMed Central

    Ward, Kate A.; Armstrong, Paul; Iwasenko, Jenna M.; Dwyer, Dominic E.

    2010-01-01

    To determine the extent and pattern of influenza transmission and effectiveness of containment measures, we investigated dual outbreaks of pandemic (H1N1) 2009 and influenza A (H3N2) that had occurred on a cruise ship in May 2009. Of 1,970 passengers and 734 crew members, 82 (3.0%) were infected with pandemic (H1N1) 2009 virus, 98 (3.6%) with influenza A (H3N2) virus, and 2 (0.1%) with both. Among 45 children who visited the ship’s childcare center, infection rate for pandemic (H1N1) 2009 was higher than that for influenza A (H3N2) viruses. Disembarked passengers reported a high level of compliance with isolation and quarantine recommendations. We found 4 subsequent cases epidemiologically linked to passengers but no evidence of sustained transmission to the community or passengers on the next cruise. Among this population of generally healthy passengers, children seemed more susceptible to pandemic (H1N1) 2009 than to influenza (H3N2) viruses. Intensive disease control measures successfully contained these outbreaks. PMID:21029531

  16. Influenza vaccination of HIV-1-positive and HIV-1-negative former intravenous drug users.

    PubMed

    Amendola, A; Boschini, A; Colzani, D; Anselmi, G; Oltolina, A; Zucconi, R; Begnini, M; Besana, S; Tanzi, E; Zanetti, A R

    2001-12-01

    The immunogenicity of an anti-influenza vaccine was assessed in 409 former intravenous drug user volunteers and its effect on the levels of HIV-1 RNA, proviral DNA and on CD4+ lymphocyte counts in a subset HIV-1-positive subjects was measured. HIV-1-positive individuals (n = 72) were divided into three groups on the basis of their CD4+ lymphocyte counts, while the 337 HIV-1-negative participants were allocated into group four. Haemagglutination inhibiting (HI) responses varied from 45.8 to 70% in the HIV-1-positive subjects and were significantly higher in group four (80.7% responses to the H1N1 strain, 81.6% to the H3N2 strain, and 83% to the B strain). The percentage of subjects with HI protective antibody titres (> or = 1:40) increased significantly after vaccination, especially in HIV-1 uninfected subjects. Immunization caused no significant changes in CD4+ counts and in neither plasma HIV-1 RNA nor proviral DNA levels. Therefore, vaccination against influenza may benefit persons infected by HIV-1. Copyright 2001 Wiley-Liss, Inc.

  17. New genetic variants of influenza A(H1N1)pdm09 detected in Cuba during 2011-2013.

    PubMed

    Arencibia, Amely; Acosta, Belsy; Muné, Mayra; Valdés, Odalys; Fernandez, Leandro; Medina, Isel; Savón, Clara; Oropesa, Suset; Gonzalez, Grehete; Roque, Rosmery; Gonzalez, Guelsys; Hernández, Bárbara; Goyenechea, Angel; Piñón, Alexander

    2015-06-01

    Influenza A(H1N1)pdm09 virus has evolved continually since its emergence in 2009. For influenza virus strains, genetic changes occurring in HA1 domain of the hemagglutinin cause the emergence of new variants. The aim of our study is to establish genetic associations between 35 A(H1N1)pdm09 viruses circulating in Cuba in 2011-2012 and 2012-2013 seasons, and A/California/07/2009 strain recommended by WHO as the H1N1 component of the influenza vaccine. The phylogenetic analysis revealed the circulation of clades 3, 6A, 6B, 6C and 7. Mutations were detected in the antigenic site or in the receptor-binding domains of HA1 segment, including S174P, S179N, K180Q, S202T, S220T and R222K. Substitutions S174P, S179N, K180Q and R222K were detected in Cuban strains for the first time. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Antigenicity of the 2015-2016 seasonal H1N1 human influenza virus HA and NA proteins.

    PubMed

    Clark, Amelia M; DeDiego, Marta L; Anderson, Christopher S; Wang, Jiong; Yang, Hongmei; Nogales, Aitor; Martinez-Sobrido, Luis; Zand, Martin S; Sangster, Mark Y; Topham, David J

    2017-01-01

    Antigenic drift of the hemagglutinin (HA) and neuraminidase (NA) influenza virus proteins contributes to reduced vaccine efficacy. To analyze antigenic drift in human seasonal H1N1 viruses derived from the 2009 pandemic H1N1 virus (pH1N1-like viruses) accounts for the limited effectiveness (around 40%) of vaccination against pH1N1-like viruses during the 2015-2016 season, nasal washes/swabs collected from adult subjects in the Rochester, NY area, were used to sequence and isolate the circulating viruses. The HA and NA proteins from viruses circulating during the 2015-2016 season encoded eighteen and fourteen amino acid differences, respectively, when compared to A/California/04/2009, a strain circulating at the origin of the 2009 pandemic. The circulating strains belonged to subclade 6B.1, defined by HA amino acid substitutions S101N, S179N, and I233T. Hemagglutination-inhibiting (HAI) and HA-specific neutralizing serum antibody (Ab) titers from around 50% of pH1N1-like virus-infected subjects and immune ferrets were 2-4 fold lower for the 2015-2016 circulating strains compared to the vaccine strain. In addition, using a luminex-based mPlex HA assay, the binding of human sera from subjects infected with pH1N1-like viruses to the HA proteins from circulating and vaccine strains was not identical, strongly suggesting antigenic differences in the HA protein. Additionally, NA inhibition (NAI) Ab titers in human sera from pH1N1-like virus-infected subjects increased after the infection and there were measurable antigenic differences between the NA protein of circulating strains and the vaccine strain using both ferret and human antisera. Despite having been vaccinated, infected subjects exhibited low HAI Ab titers against the vaccine and circulating strains. This suggests that poor responses to the H1N1 component of the vaccine as well as antigenic differences in the HA and NA proteins of currently circulating pH1N1-like viruses could be contributing to risk of

  19. Likely correlation between sources of information and acceptability of A/H1N1 swine-origin influenza virus vaccine in Marseille, France.

    PubMed

    Nougairède, Antoine; Lagier, Jean-Christophe; Ninove, Laetitia; Sartor, Catherine; Badiaga, Sékéné; Botelho, Elizabeth; Brouqui, Philippe; Zandotti, Christine; De Lamballerie, Xavier; La Scola, Bernard; Drancourt, Michel; Gould, Ernest A; Charrel, Rémi N; Raoult, Didier

    2010-06-25

    In France, there was a reluctance to accept vaccination against the A/H1N1 pandemic influenza virus despite government recommendation and investment in the vaccine programme. We examined the willingness of different populations to accept A/H1N1 vaccination (i) in a French hospital among 3315 employees immunized either by in-house medical personnel or mobile teams of MDs and (ii) in a shelter housing 250 homeless persons. Google was used to assess the volume of enquiries concerning incidence of influenza. We analyzed the information on vaccination provided by Google, the website of the major French newspapers, and PubMed. Two trust Surveys were used to assess public opinion on the trustworthiness of people in different professions. Paramedics were significantly more reluctant to accept immunisation than qualified medical staff. Acceptance was significantly increased when recommended directly by MDs. Anecdotal cases of directly observed severe infections were followed by enhanced acceptance of paramedical staff. Scientific literature was significantly more in favour of vaccination than Google and French newspaper websites. In the case of the newspaper websites, information correlated with their recognised political reputations, although they would presumably claim independence from political bias. The Trust Surveys showed that politicians were highly dis-trusted in contrast with doctors and pharmacists who were considered much more trustworthy. The low uptake of the vaccine could reflect failure to convey high quality medical information and advice relating to the benefits of being vaccinated. We believe that the media and internet contributed to this problem by raising concerns within the general population and that failure to involve GPs in the control programme may have been a mistake. GPs are highly regarded by the public and can provide face-to-face professional advice and information. The top-down strategy of vaccine programme management and information

  20. Likely Correlation between Sources of Information and Acceptability of A/H1N1 Swine-Origin Influenza Virus Vaccine in Marseille, France

    PubMed Central

    Ninove, Laetitia; Sartor, Catherine; Badiaga, Sékéné; Botelho, Elizabeth; Brouqui, Philippe; Zandotti, Christine; De Lamballerie, Xavier; La Scola, Bernard; Drancourt, Michel; Gould, Ernest A.; Charrel, Rémi N.; Raoult, Didier

    2010-01-01

    Background In France, there was a reluctance to accept vaccination against the A/H1N1 pandemic influenza virus despite government recommendation and investment in the vaccine programme. Methods and Findings We examined the willingness of different populations to accept A/H1N1vaccination (i) in a French hospital among 3315 employees immunized either by in-house medical personnel or mobile teams of MDs and (ii) in a shelter housing 250 homeless persons. Google was used to assess the volume of enquiries concerning incidence of influenza. We analyzed the information on vaccination provided by Google, the website of the major French newspapers, and PubMed. Two trust Surveys were used to assess public opinion on the trustworthiness of people in different professions. Paramedics were significantly more reluctant to accept immunisation than qualified medical staff. Acceptance was significantly increased when recommended directly by MDs. Anecdotal cases of directly observed severe infections were followed by enhanced acceptance of paramedical staff. Scientific literature was significantly more in favour of vaccination than Google and French newspaper websites. In the case of the newspaper websites, information correlated with their recognised political reputations, although they would presumably claim independence from political bias. The Trust Surveys showed that politicians were highly distrusted in contrast with doctors and pharmacists who were considered much more trustworthy. Conclusions The low uptake of the vaccine could reflect failure to convey high quality medical information and advice relating to the benefits of being vaccinated. We believe that the media and internet contributed to this problem by raising concerns within the general population and that failure to involve GPs in the control programme may have been a mistake. GPs are highly regarded by the public and can provide face-to-face professional advice and information. The top-down strategy of vaccine

  1. System factors to explain H1N1 state vaccination rates for adults in US emergency response to pandemic.

    PubMed

    Davila-Payan, Carlo; Swann, Julie; Wortley, Pascale M

    2014-05-23

    During the 2009-2010 H1N1 pandemic, vaccine in short supply was allocated to states pro rata by population, yet the vaccination rates of adults differed by state. States also differed in their campaign processes and decisions. Analyzing the campaign provides an opportunity to identify specific approaches that may result in higher vaccine uptake in a future event of this nature. To determine supply chain and system factors associated with higher state H1N1 vaccination coverage for adults in a system where vaccine was in short supply. Regression analysis of factors predicting state-specific H1N1 vaccination coverage in adults. Independent variables included state campaign information, demographics, preventive or health-seeking behavior, preparedness funding, providers, state characteristics, and H1N1-specific state data. The best model explained the variation in state-specific adult vaccination coverage with an adjusted R-squared of 0.76. We found that higher H1N1 coverage of adults is associated with program aspects including shorter lead-times (i.e., the number of days between when doses were allocated to a state and were shipped, including the time for states to order the doses) and less vaccine directed to specialist locations. Higher vaccination coverage is also positively associated with the maximum number of ship-to locations, past seasonal influenza vaccination coverage, the percentage of women with a Pap smear, the percentage of the population that is Hispanic, and negatively associated with a long duration of the epidemic peak. Long lead-times may be a function of system structure or of efficiency and may suggest monitoring or redesign of distribution processes. Sending vaccine to sites with broad access could be useful when covering a general population. Existing infrastructure may be reflected in the maximum number of ship-to locations, so strengthening routine influenza vaccination programs may help during emergency vaccinations also. Future research

  2. Divergent genetic evolution of hemagglutinin in influenza A H1N1 and A H1N2 subtypes isolated in the south-France since the winter of 2001-2002.

    PubMed

    Al Faress, Shaker; Cartet, Gaëlle; Ferraris, Olivier; Norder, Helene; Valette, Martine; Lina, Bruno

    2005-07-01

    Influenza A viruses are divided into subtypes based on their hemagglutinin (H1 to H15) and neuraminidase (N1 to N9) glycoproteins. Of these, three A subtypes H1N1, H3N2 and H1N2 circulate in the human population. Influenza A viruses display a high antigenic variability called "antigenic drift" which allows the virus to escape antibody neutralization. Evaluate the mutations apparition that might predict a divergent antigenic evolution of hemagglutinin in influenza A H1N1 and A H1N2 viruses. During the three winters of 2001-2002 to 2003-2004, 58 A H1N1 and 23 A H1N2 subtypes have been isolated from patients with influenza-like illness in the south of France. The HA1 region was analyzed by RT-PCR and subsequently sequenced to compare the HA1 genetic evolution of influenza A H1N1 and A H1N2 subtypes. Our results showed that 28 amino acid substitutions have accumulated in the HA1 region since the circulation of A/New Caledonia/20/99-like viruses in France. Of these, fifteen were located in four antigenic sites (B, C, D and E). Six of them were observed only in the A H1N2 isolates, six only in the A H1N1 isolates and three in both subtypes. Furthermore, nine of twenty two A H1N2 isolates from the winter of 2002-2003 shared a T90A amino acid change which has not been observed in any A H1N1 isolate; resulting in the introduction of a new glycosylation site close to the antigenic site E. This might mask some antigenic E determinants and therefore, modify the A H1N2 antigenicity. The divergent genetic evolution of hemagglutinin may ultimately lead to a significant different antigenicity between A H1N1 and A H1N2 subtypes that would require the introduction of a new subtype in the vaccine batches.

  3. Risk Factors for Influenza A(H1N1)pdm09 among Students, Beijing, China

    PubMed Central

    Zheng, Yang; Duan, Wei; Yang, Peng; Zhang, Yi; Wang, Xiaoli; Zhang, Li; Liyanage, Surabhi S.

    2013-01-01

    To identify risk factors associated with influenza A(H1N1)pdm09 among students in Beijing, China, we conducted a case–control study. Participants (304 case-patients and 608 controls, age range 6–19 years) were interviewed by using a standardized questionnaire. We found that in addition to vaccination, nonpharmaceutical interventions appeared to be protective. PMID:23347500

  4. Oseltamivir-resistant pandemic influenza a (H1N1) 2009 viruses in Spain.

    PubMed

    Ledesma, Juan; Vicente, Diego; Pozo, Francisco; Cilla, Gustavo; Castro, Sonia Pérez; Fernández, Jonathan Suárez; Ruiz, Mercedes Pérez; Navarro, José María; Galán, Juan Carlos; Fernández, Mirian; Reina, Jordi; Larrauri, Amparo; Cuevas, María Teresa; Casas, Inmaculada; Breña, Pilar Pérez

    2011-07-01

    Pandemic influenza A (H1N1) 2009 virus appeared in Spain on April 25, 2009 for the first time. This new virus was adamantane-resistant but it was sensitive to neuraminidase (NA) inhibitors oseltamivir and zanamivir. To detect oseltamivir-resistant pandemic influenza A (H1N1) 2009 viruses by the Spanish Influenza Surveillance System (SISS) and a possible spread of oseltamivir-resistant viruses in Spain since starting of the pandemic situation. A total of 1229 respiratory samples taken from 413 severe and 766 non-severe patients with confirmed viral detection of pandemic influenza A (H1N1) 2009 viruses from different Spanish regions were analyzed for the specific detection of the H275Y mutation in NA between April 2009 and May 2010. H275Y NA substitution was found in 8 patients infected with pandemic influenza A (H1N1) 2009 viruses collected in November and December 2009 and in January 2010. All oseltamivir-resistant viruses were detected in severe patients (8/413, 1.93%) who previously received treatment with oseltamivir. Six of these patients were immunocompromised. In Spain, the number of oseltamivir-resistant pandemic influenza A (H1N1) 2009 viruses is until now very low. No evidence for any spread of oseltamivir-resistant H1N1 viruses is achieved in our Country. Copyright © 2011 Elsevier B.V. All rights reserved.

  5. Pregnant and recently pregnant women's perceptions about influenza a pandemic (H1N1) 2009: implications for public health and provider communication.

    PubMed

    Lynch, Molly M; Mitchell, Elizabeth W; Williams, Jennifer L; Brumbaugh, Kelly; Jones-Bell, Michelle; Pinkney, Debra E; Layton, Christine M; Mersereau, Patricia W; Kendrick, Juliette S; Medina, Paula Eguino; Smith, Lucia Rojas

    2012-11-01

    The objective of this study was to explore pregnant and recently pregnant women's perceptions of influenza vaccine and antivirals during the 2009 H1N1 pandemic. We conducted 18 focus groups with pregnant and recently pregnant women in three US cities in September 2009. Participants were segmented into groups by insurance status (no or public insurance vs. private insurance), vaccine attitudes (higher vs. lower likelihood of acceptance of any vaccines, not only influenza vaccines), and parity (first child vs. other children in the home) based on information they provided on the screening questionnaire at the time of recruitment. We found that women are not well informed about influenza vaccinations and antiviral medicine and have significant concerns about taking them during pregnancy. An interest in their infant's well-being, however, can be strong motivation to adopt preventive recommendations, including vaccination. A woman's health care provider is a highly trusted source of information about the 2009 H1N1. Pregnant women have unique communication needs for influenza. Messages directing pregnant women to adopt public health recommendations, particularly for vaccination or prophylactic medication should include a detailed description of the benefits or lack of risk to the fetus and the safety of breastfeeding. Additionally, messages should recognize that pregnant women are taught to be selective about taking medication and provide a clear rationale for why the medicine or vaccine is necessary.

  6. Evaluation of seasonal influenza vaccines for H1N1pdm09 and type B viruses based on a replication-incompetent PB2-KO virus.

    PubMed

    Ui, Hiroki; Yamayoshi, Seiya; Uraki, Ryuta; Kiso, Maki; Oishi, Kohei; Murakami, Shin; Mimori, Shigetaka; Kawaoka, Yoshihiro

    2017-04-04

    Vaccination is the first line of protection against influenza virus infection in humans. Although inactivated and live-attenuated vaccines are available, each vaccine has drawbacks in terms of immunogenicity and safety. To overcome these issues, our group has developed a replication-incompetent PB2-knockout (PB2-KO) influenza virus that replicates only in PB2-expressing cells. Here we generated PB2-KO viruses possessing the hemagglutinin (HA) and neuraminidase (NA) segments from H1N1pdm09 or type B viruses and tested their vaccine potential. The two PB2-KO viruses propagated efficiently in PB2-expressing cells, and expressed chimeric HA as expected. Virus-specific IgG and IgA antibodies were detected in mice immunized with the viruses, and the immunized mice showed milder clinical signs and/or lower virus replication levels in the respiratory tract upon virus challenge. Our results indicate that these PB2-KO viruses have potential as vaccine candidates. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Antibody Affinity Against 2009 A/H1N1 Influenza and Pandemrix Vaccine Nucleoproteins Differs Between Childhood Narcolepsy Patients and Controls.

    PubMed

    Lind, Alexander; Freyhult, Eva; Ramelius, Anita; Olsson, Tomas; Arnheim-Dahlström, Lisen; Lamb, Favelle; Khademi, Mohsen; Ambati, Aditya; Maeurer, Markus; Lima Bomfim, Izaura; Fink, Katharina; Fex, Malin; Törn, Carina; Elding Larsson, Helena; Lernmark, Åke

    2017-10-01

    Increased narcolepsy incidence was observed in Sweden following the 2009 influenza vaccination with Pandemrix ® . A substitution of the 2009 nucleoprotein for the 1934 variant has been implicated in narcolepsy development. The aims were to determine (a) antibody levels toward wild-type A/H1N1-2009[A/California/04/2009(H1N1)] (NP-CA2009) and Pandemrix-[A/Puerto Rico/8/1934(H1N1)] (NP-PR1934) nucleoproteins in 43 patients and 64 age-matched controls; (b) antibody affinity in reciprocal competitive assays in 11 childhood narcolepsy patients compared with 21 age-matched controls; and (c) antibody levels toward wild-type A/H1N1-2009[A/California/04/2009(H1N1)] (H1N1 NS1), not a component of the Pandemrix vaccine. In vitro transcribed and translated 35 S-methionine-labeled H1N1 influenza A virus proteins were used in radiobinding reciprocal competition assays to estimate antibody levels and affinity (Kd). Childhood patients had higher NP-CA2009 (p = 0.0339) and NP-PR1934 (p = 0.0246) antibody levels compared with age-matched controls. These childhood controls had lower NP-CA2009 (p = 0.0221) and NP-PR1934 (p = 0.00619) antibodies compared with controls 13 years or older. In contrast, in patients 13 years or older, the levels of NP-PR1934 (p = 0.279) and NP-CA2009 (p = 0.0644) antibodies did not differ from the older controls. Childhood antibody affinity (Kd) against NP-CA2009 was comparable between controls (68 ng/mL) and patients (74 ng/mL; p = 0.21) with NP-CA2009 and NP-PR1934 displacement (controls: 165 ng/mL; patients: 199 ng/mL; p = 0.48). In contrast, antibody affinity against NP-PR1934 was higher in controls with either NP-PR1934 (controls: 9 ng/mL; patients: 20 ng/mL; p = 0.0031) or NP-CA2009 (controls: 14 ng/mL; patients: 23 ng/mL; p = 0.0048). A/H1N1-NS1 antibodies were detected in 0/43 of the narcolepsy patients compared with 3/64 (4.7%) controls (p = 0.272). Similarly, none (0/11) of the childhood

  8. Canine susceptibility to human influenza viruses (A/pdm 09H1N1, A/H3N2 and B).

    PubMed

    Song, Daesub; Kim, Hyekwon; Na, Woonsung; Hong, Minki; Park, Seong-Jun; Moon, Hyoungjoon; Kang, Bokyu; Lyoo, Kwang-Soo; Yeom, Minjoo; Jeong, Dae Gwin; An, Dong-Jun; Kim, Jeong-Ki

    2015-02-01

    We investigated the infectivity and transmissibility of the human seasonal H3N2, pandemic (pdm) H1N1 (2009) and B influenza viruses in dogs. Dogs inoculated with human seasonal H3N2 and pdm H1N1 influenza viruses exhibited nasal shedding and were seroconverted against the viruses; this did not occur in the influenza B virus-inoculated dogs. Transmission of human H3N2 virus between dogs was demonstrated by observing nasal shedding and seroconversion in naïve dogs after contact with inoculated dogs. The seroprevalence study offered evidence of human H3N2 infection occurring in dogs since 2008. Furthermore, serological evidence of pdm H1N1 influenza virus infection alone and in combination with canine H3N2 virus was found in the serum samples collected from field dogs during 2010 and 2011. Our results suggest that dogs may be hosts for human seasonal H3N2 and pdm H1N1 influenza viruses. © 2015 The Authors.

  9. Low pathogenic avian influenza (H9N2) in chicken: Evaluation of an ancestral H9-MVA vaccine.

    PubMed

    Ducatez, Mariette F; Becker, Jens; Freudenstein, Astrid; Delverdier, Maxence; Delpont, Mattias; Sutter, Gerd; Guérin, Jean-Luc; Volz, Asisa

    2016-06-30

    Modified Vaccinia Ankara (MVA) has proven its efficacy as a recombinant vector vaccine for numerous pathogens including influenza virus. The present study aimed at evaluating a recombinant MVA candidate vaccine against low pathogenic avian influenza virus subtype H9N2 in the chicken model. As the high genetic and antigenic diversity of H9N2 viruses increases vaccine design complexity, one strategy to widen the range of vaccine coverage is to use an ancestor sequence. We therefore generated a recombinant MVA encoding for the gene sequence of an ancestral hemagglutinin H9 protein (a computationally derived amino acid sequence of the node of the H9N2 G1 lineage strains was obtained using the ANCESCON program). We analyzed the genetics and the growth properties of the MVA vector virus confirming suitability for use under biosafety level 1 and tested its efficacy when applied either as an intra-muscular (IM) or an oral vaccine in specific pathogen free chickens challenged with A/chicken/Tunisia/12/2010(H9N2). Two control groups were studied in parallel (unvaccinated and inoculated birds; unvaccinated and non-inoculated birds). IM vaccinated birds seroconverted as early as four days post vaccination and neutralizing antibodies were detected against A/chicken/Tunisia/12/2010(H9N2) in all the birds before challenge. The role of local mucosal immunity is unclear here as no antibodies were detected in eye drop or aerosol vaccinated birds. Clinical signs were not detected in any of the infected birds even in absence of vaccination. Virus replication was observed in both vaccinated and unvaccinated chickens, suggesting the MVA-ancestral H9 vaccine may not stop virus spread in the field. However vaccinated birds showed less histological damage, fewer influenza-positive cells and shorter virus shedding than their unvaccinated counterparts. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Interim estimates of the effectiveness of the influenza vaccine against A(H3N2) influenza in adults in South Korea, 2016-2017 season.

    PubMed

    Noh, Ji Yun; Lim, Sooyeon; Song, Joon Young; Choi, Won Suk; Jeong, Hye Won; Heo, Jung Yeon; Lee, Jacob; Seo, Yu Bin; Lee, Jin-Soo; Wie, Seong Heon; Kim, Young Keun; Park, Kyung Hwa; Jung, Sook-In; Kim, Shin Woo; Lee, Sun Hee; Lee, Han Sol; Yoon, Young Hoon; Cheong, Hee Jin; Kim, Woo Joo

    2017-01-01

    In the 2016-2017 season, the A(H3N2) influenza epidemic presented an unusual early peak pattern compared with past seasons in South Korea. The interim vaccine effectiveness (VE) of influenza vaccination in preventing laboratory-confirmed influenza was estimated using test-negative design through the tertiary hospital-based influenza surveillance system in South Korea. From 1 September, 2016 to 7 January, 2017, adjusted VE of influenza vaccination in preventing laboratory-confirmed A(H3N2) was -52.1% (95% confidence interval [CI], -147.2 to 6.4); -70.0% (95% CI, -212.0 to 7.4) in 19-64 years and 4.3% (95% CI, -137.8 to 61.5) in the elderly. Circulating A(H3N2) viruses belonged to the three phylogenetic subclades of 3C.2a, differently to A/Hong Kong/4801/2014, the current vaccine strain. Amino acid substitutions in hemagglutinin of circulating viruses seem to contribute to low VE. In conclusion, interim VE analysis presented that the protection of laboratory-confirmed influenza by seasonal influenza vaccination did not show the statistical significance in South Korea in the 2016-2017 influenza season.

  11. Isolation and genetic characterization of avian-like H1N1 and novel ressortant H1N2 influenza viruses from pigs in China.

    PubMed

    Yu, Hai; Zhang, Peng-Chao; Zhou, Yan-Jun; Li, Guo-Xin; Pan, Jie; Yan, Li-Ping; Shi, Xiao-Xiao; Liu, Hui-Li; Tong, Guang-Zhi

    2009-08-21

    As pigs are susceptible to both human and avian influenza viruses, they have been proposed to be intermediate hosts or mixing vessels for the generation of pandemic influenza viruses through reassortment or adaptation to the mammalian host. In this study, we reported avian-like H1N1 and novel ressortant H1N2 influenza viruses from pigs in China. Homology and phylogenetic analyses showed that the H1N1 virus (A/swine/Zhejiang/1/07) was closely to avian-like H1N1 viruses and seemed to be derived from the European swine H1N1 viruses, which was for the first time reported in China; and the two H1N2 viruses (A/swine/Shanghai/1/07 and A/swine/Guangxi/13/06) were novel ressortant H1N2 influenza viruses containing genes from the classical swine (HA, NP, M and NS), human (NA and PB1) and avian (PB2 and PA) lineages, which indicted that the reassortment among human, avian, and swine influenza viruses had taken place in pigs in China and resulted in the generation of new viruses. The isolation of avian-like H1N1 influenza virus originated from the European swine H1N1 viruses, especially the emergence of two novel ressortant H1N2 influenza viruses provides further evidence that pigs serve as intermediate hosts or "mixing vessels", and swine influenza virus surveillance in China should be given a high priority.

  12. Phase II, randomized, open, controlled study of AS03-adjuvanted H5N1 pre-pandemic influenza vaccine in children aged 3 to 9 years: follow-up of safety and immunogenicity persistence at 24 months post-vaccination.

    PubMed

    Díez-Domingo, Javier; Baldó, José-María; Planelles-Catarino, Maria Victoria; Garcés-Sánchez, María; Ubeda, Isabel; Jubert-Rosich, Angels; Marès, Josep; Garcia-Corbeira, Pilar; Moris, Philippe; Teko, Maurice; Vanden Abeele, Carline; Gillard, Paul

    2015-03-01

    An AS03-adjuvanted H5N1 influenza vaccine elicited broad and persistent immune responses with an acceptable safety profile up to 6 months following the first vaccination in children aged 3-9 years. In this follow-up of the Phase II study, we report immunogenicity persistence and safety at 24 months post-vaccination in children aged 3-9 years. The randomized, open-label study assessed two doses of H5N1 A/Vietnam/1194/2004 influenza vaccine (1·9 μg or 3·75 μg hemagglutinin antigen) formulated with AS03A or AS03B (11·89 mg or 5·93 mg tocopherol, respectively). Control groups received seasonal trivalent influenza vaccine. Safety was assessed prospectively and included potential immune-mediated diseases (pIMDs). Immunogenicity was assessed by hemagglutination-inhibition assay 12 and 24 months after vaccination; cross-reactivity and cell-mediated responses were also assessed. (NCT00502593). The safety population included 405 children. Over 24 months, five events fulfilled the criteria for pIMDs, of which four occurred in H5N1 vaccine recipients, including uveitis (n = 1) and autoimmune hepatitis (n = 1), which were considered to be vaccine-related. Overall, safety profiles of the vaccines were clinically acceptable. Humoral immune responses at 12 and 24 months were reduced versus those observed after the second dose of vaccine, although still within the range of those observed after the first dose. Persistence of cell-mediated immunity was strong, and CD4(+) T cells with a TH 1 profile were observed. Two doses of an AS03-adjuvanted H5N1 influenza vaccine in children showed low but persistent humoral immune responses and a strong persistence of cell-mediated immunity, with clinically acceptable safety profiles up to 24 months following first vaccination. © 2014 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.

  13. Antigenic Patterns and Evolution of the Human Influenza A (H1N1) Virus.

    PubMed

    Liu, Mi; Zhao, Xiang; Hua, Sha; Du, Xiangjun; Peng, Yousong; Li, Xiyan; Lan, Yu; Wang, Dayan; Wu, Aiping; Shu, Yuelong; Jiang, Taijiao

    2015-09-28

    The influenza A (H1N1) virus causes seasonal epidemics that result in severe illnesses and deaths almost every year. A deep understanding of the antigenic patterns and evolution of human influenza A (H1N1) virus is extremely important for its effective surveillance and prevention. Through development of antigenicity inference method for human influenza A (H1N1), named PREDAC-H1, we systematically mapped the antigenic patterns and evolution of the human influenza A (H1N1) virus. Eight dominant antigenic clusters have been inferred for seasonal H1N1 viruses since 1977, which demonstrated sequential replacements over time with a similar pattern in Asia, Europe and North America. Among them, six clusters emerged first in Asia. As for China, three of the eight antigenic clusters were detected in South China earlier than in North China, indicating the leading role of South China in H1N1 transmission. The comprehensive view of the antigenic evolution of human influenza A (H1N1) virus can help formulate better strategy for its prevention and control.

  14. Challenge of N95 Filtering Facepiece Respirators with Viable H1N1 Influenza Aerosols

    PubMed Central

    Harnish, Delbert A.; Heimbuch, Brian K.; Husband, Michael; Lumley, April E.; Kinney, Kimberly; Shaffer, Ronald E.; Wander, Joseph D.

    2015-01-01

    OBJECTIVE Specification of appropriate personal protective equipment for respiratory protection against influenza is somewhat controversial. In a clinical environment, N95 filtering facepiece respirators (FFRs) are often recommended for respiratory protection against infectious aerosols. This study evaluates the ability of N95 FFRs to capture viable H1N1 influenza aerosols. METHODS Five N95 FFR models were challenged with aerosolized viable H1N1 influenza and inert polystyrene latex particles at continuous flow rates of 85 and 170 liters per minute. Virus was assayed using Madin-Darby canine kidney cells to determine the median tissue culture infective dose (TCID50). Aerosols were generated using a Collison nebulizer containing H1N1 influenza virus at 1 × 108 TCID50/mL. To determine filtration efficiency, viable sampling was performed upstream and downstream of the FFR. RESULTS N95 FFRs filtered 0.8-µm particles of both H1N1 influenza and inert origins with more than 95% efficiency. With the exception of 1 model, no statistically significant difference in filtration performance was observed between influenza and inert particles of similar size. Although statistically significant differences were observed for 2 models when comparing the 2 flow rates, the differences have no significance to protection. CONCLUSIONS This study empirically demonstrates that a National Institute for Occupational Safety and Health–approved N95 FFR captures viable H1N1 influenza aerosols as well as or better than its N95 rating, suggesting that a properly fitted FFR reduces inhalation exposure to airborne influenza virus. This study also provides evidence that filtration efficiency is based primarily on particle size rather than the nature of the particle’s origin. PMID:23571366

  15. Churg-Strauss Syndrome Following Vaccination Against 2010 Influenza A (H1N1): A Case Report.

    PubMed

    Fu, Mu-Hui; Tsai, Wan-Chen; Lan, Jui; Lu, Cheng-Hsien; Lee, Lian-Hui; Huang, Chih-Cheng

    2014-09-01

    Churg-Strauss syndrome (CSS) is a systemic inflammatory disorder characterized by asthma, transient pulmonary infiltration, hyper-eosinophilia, and systemic vasculitis. Reported triggering factors include infections, drugs, allergic desensitization, and vaccinations, although cases involving the latter two are extremely rare. Herein, we describe a patient who developed CSS after receiving an H1N1 vaccination. A 55-year-old woman presented with fever, skin eruptions, and sensory impairment of her feet within one week after an H1N1 vaccine injection. A chest X-ray showed pulmonary infiltrations in both lower lung fields. Eosinophilia was noted in a hematological test, and an electrophysiological study revealed a pattern of mononeuritis multiplex. A skin biopsy was performed which revealed palisading necrotizing granuloma around a degenerated dermis and eosinophilic infiltration of the blood vessel walls. These findings combined with the hematological and electrophysiological findings met the criteria of CSS according to the American College of Rheumatology. The patient recovered well after steroid treatment. This case highlights the possibility that the H1N1 vaccination can trigger CSS. Due to the rarity of reported autoimmune events after vaccine administration and the obscure causal association between autoimmunity and a vaccine, further post-marketing surveillance and research are necessary to clarify the relationship and identify risk factors.

  16. Waning vaccine protection against influenza A (H3N2) illness in children and older adults during a single season.

    PubMed

    Belongia, Edward A; Sundaram, Maria E; McClure, David L; Meece, Jennifer K; Ferdinands, Jill; VanWormer, Jeffrey J

    2015-01-01

    Recent studies have suggested that vaccine-induced protection against influenza may decline within one season. We reanalyzed data from a study of influenza vaccine effectiveness to determine if time since vaccination was an independent predictor of influenza A (H3N2). Patients with acute respiratory illness were actively recruited during the 2007-2008 season. Respiratory swabs were tested for influenza, and vaccination dates were determined by a validated immunization registry. The association between influenza RT-PCR result and vaccination interval (days) was examined using multivariable logistic regression, adjusting for calendar time, age and other confounders. There were 629 vaccinated participants, including 177 influenza A (H3N2) cases and 452 test negative controls. The mean (SD) interval from vaccination to illness onset was 101.7 (25.9) days for influenza cases and 93.0 (29.9) days for controls. There was a significant association between vaccination interval and influenza result in the main effects model. The adjusted odds ratio (aOR) for influenza was 1.12 (CI 1.01, 1.26) for every 14 day increase in the vaccination interval. Age modified the association between vaccination interval and influenza (p=0.005 for interaction). Influenza was associated with increasing vaccination interval in young children and older adults, but not in adolescents or non-elderly adults. Similar results were found when calendar week of vaccine receipt was assessed as the primary exposure variable. Identification of influenza A (H3N2) was associated with increasing time since vaccination among young children and older adults during a single influenza season. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  17. Use of a tetanus toxoid marker to allow differentiation of infected from vaccinated poultry without affecting the efficacy of a H5N1 avian influenza virus vaccine.

    PubMed

    James-Berry, C M; Middleton, D; Mansfield, J P; Fenwick, S G; Ellis, T M

    2010-10-30

    Tetanus toxoid (TT) was assessed as a positive marker for avian influenza (AI) virus vaccination in chickens, in a vaccination and challenge study. Chickens were vaccinated twice with inactivated AI H5N2 virus vaccine, and then challenged three weeks later with highly pathogenic AI H5N1 virus. Vaccinated chickens were compared with other groups that were either sham-vaccinated or vaccinated with virus with the TT marker. All sham-vaccinated chickens died by 36 hours postinfection, whereas all vaccinated chickens, with or without the TT marker, were protected from morbidity and mortality following exposure to the challenge virus. Serological testing for H5-specific antibodies identified anamnestic responses to H5 in some of the vaccinated birds, indicating active virus infection.

  18. A consensus-hemagglutinin-based vaccine delivered by an attenuated Salmonella mutant protects chickens against heterologous H7N1 influenza virus.

    PubMed

    Hyoung, Kim Je; Hajam, Irshad Ahmed; Lee, John Hwa

    2017-06-13

    H7N3 and H7N7 are highly pathogenic avian influenza (HPAI) viruses and have posed a great threat not only for the poultry industry but for the human health as well. H7N9, a low pathogenic avian influenza (LPAI) virus, is also highly pathogenic to humans, and there is a great concern that these H7 subtypes would acquire the ability to spread efficiently between humans, thereby becoming a pandemic threat. A vaccine candidate covering all the three subtypes must, therefore, be an integral part of any pandemic preparedness plan. To address this need, we constructed a consensus hemagglutinin (HA) sequence of H7N3, H7N7, and H7N9 based on the data available in the NCBI in early 2012-2015. This artificial sequence was then optimized for protein expression before being transformed into an attenuated auxotrophic mutant of Salmonella Typhimurium, JOL1863 strain. Immunizing chickens with JOL1863, delivered intramuscularly, nasally or orally, elicited efficient humoral and cell mediated immune responses, independently of the route of vaccination. Our results also showed that JOL1863 deliver efficient maturation signals to chicken monocyte derived dendritic cells (MoDCs) which were characterized by upregulation of costimulatory molecules and higher cytokine induction. Moreover, immunization with JOL1863 in chickens conferred a significant protection against the heterologous LPAI H7N1 virus challenge as indicated by reduced viral sheddings in the cloacal swabs. We conclude that this vaccine, based on a consensus HA, could induce broader spectrum of protection against divergent H7 influenza viruses and thus warrants further study.

  19. Epidemiology and Clinical Complication Patterns of Influenza A (H1N1 Virus) in Northern Saudi Arabia

    PubMed Central

    Altayep, Kheder Mohamed; Ahmed, Hussain Gadelakrim; a Tallaa, Amjad Tallaa; Alzayed, Ahmad Soud; Alshammari, Aqeel Jazzaa; Ali Talla, Ayman Talla

    2017-01-01

    The aim of the present study is to describe epidemiologic and clinical presentation, clinical complications and outcomes of patients diagnosed with influenza A infection (H1N1) during a one-year period. We retrospectively investigated 300 patients with influenza-like clinical presentation during the period January 2015 – January 2016 in King Khalid Hospital, Saudi Arabia. Fifty-four patients out of 300 (18%) were diagnosed with H1N1 virus infection; their age ranged from 7 months to 85 years, with a mean age of 25 years. Among them, 34 (63%) were males and 20 (37%) were females, with a M:F ratio of 1.70. The findings of this study show the great spread of influenza A outside the main holy cities of Saudi Arabia, and underline the absolute need for strict prevention strategies including vaccinations, public awareness and hygiene measures. PMID:28663778

  20. Autoimmune disorders after immunisation with Influenza A/H1N1 vaccines with and without adjuvant: EudraVigilance data and literature review.

    PubMed

    Isai, Alina; Durand, Julie; Le Meur, Steven; Hidalgo-Simon, Ana; Kurz, Xavier

    2012-11-19

    All suspected autoimmune disorders (AID) reported as adverse reactions to EudraVigilance from 1 October 2009 to 31 December 2010 for adjuvanted (Celtura™, Fluval P™, Focetria™ and Pandemrix™) and non-adjuvanted (Cantgrip™, Celvapan™ and Panenza™) pandemic Influenza A/H1N1 vaccines were analysed to determine whether adjuvanted vaccines were associated with higher reporting of AID than non-adjuvanted ones. AID were identified based on the corresponding MedDRA High Level Group Term. Reports of type 1 diabetes mellitus and multiple sclerosis were also included in the analysis. Causality was assessed based on WHO causality assessment for adverse events following immunisation and Brighton Collaboration criteria for Guillain-Barré syndrome (GBS), idiopathic thrombocytopenic purpura and acute disseminated encephalomyelitis. Of the 50,221 adverse reactions received in EudraVigilance for A/H1N1 vaccines (adjuvanted: 46,173, non-adjuvanted: 4048), 314 were AID (adjuvanted: 276, non-adjuvanted: 38). GBS was the AID with the highest number of reports (125, adjuvanted: 109, non-adjuvanted: 16). Reporting ratios as calculated by the percentages of AID amongst all reported adverse reactions were 0.60% (95% CI: 0.53-0.67) and 0.94% (95% CI: 0.64-1.24) for adjuvanted and non-adjuvanted vaccines, and were 0.26% (95% CI: 0.22-0.31) and 0.37% (95% CI: 0.18-0.56) in a restricted analysis based on diagnostic certainty, causal relationship and plausible temporal association. Reporting rates for all reports of AID using the estimated number of vaccinees as denominator were 6.87 (95% CI: 6.06-7.68) and 9.98 (95% CI: 6.81-13.16) per million for adjuvanted and non-adjuvanted vaccines, and 3.01 (95% CI: 2.47-3.55) and 3.94 (95% CI: 1.95-5.94) per million in the restricted analysis. These results do not suggest a difference in the reporting of AID between adjuvanted and non-adjuvanted A/H1N1 vaccines. In a literature review performed on 31 August 2011, GBS was also the AID the

  1. Impact of vaccination on infection with Vietnam H5N1 high pathogenicity avian influenza virus in hens and the eggs they lay

    USDA-ARS?s Scientific Manuscript database

    High pathogenicity avian influenza virus (HPAIV) infections in chickens decrease egg production and eggs that are laid contain HPAIV. Vaccination once or twice was examined as a way to protect chickens from Vietnamese H5N1 HPAIV. Eighty-three percent of hens without vaccination died within 3 days ...

  2. Novel triple reassortant H1N2 influenza viruses bearing six internal genes of the pandemic 2009/H1N1 influenza virus were detected in pigs in China.

    PubMed

    Qiao, Chuanling; Liu, Liping; Yang, Huanliang; Chen, Yan; Xu, Huiyang; Chen, Hualan

    2014-12-01

    The pandemic A/H1N1 influenza viruses emerged in both Mexico and the United States in March 2009, and were transmitted efficiently in the human population. Transmissions of the pandemic 2009/H1N1 virus from humans to poultry and other species of mammals were reported from several continents during the course of the 2009 H1N1 pandemic. Reassortant H1N1, H1N2, and H3N2 viruses containing genes of the pandemic 2009/H1N1 viruses appeared in pigs in some countries. In winter of 2012, a total of 2600 nasal swabs were collected from healthy pigs in slaughterhouses located throughout 10 provinces in China. The isolated viruses were subjected to genetic and antigenic analysis. Two novel triple-reassortant H1N2 influenza viruses were isolated from swine in China in 2012, with the HA gene derived from Eurasian avian-like swine H1N1, the NA gene from North American swine H1N2, and the six internal genes from the pandemic 2009/H1N1 viruses. The two viruses had similar antigenic features and some significant changes in antigenic characteristics emerged when compared to the previously identified isolates. We inferred that the novel reassortant viruses in China may have arisen from the accumulation of the three types of influenza viruses, which further indicates that swine herds serve as "mixing vessels" for influenza viruses. Influenza virus reassortment is an ongoing process, and our findings highlight the urgent need for continued influenza surveillance among swine herds. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. Influenza A(H1N1)pdm09 during air travel

    PubMed Central

    Neatherlin, John; Cramer, Elaine H.; Dubray, Christine; Marienau, Karen J.; Russell, Michelle; Sun, Hong; Whaley, Melissa; Hancock, Kathy; Duong, Krista K.; Kirking, Hannah L.; Schembri, Christopher; Katz, Jacqueline M.; Cohen, Nicole J.; Fishbein, Daniel B.

    2015-01-01

    Summary The global spread of the influenza A(H1N1)pdm09 virus (pH1N1) associated with travelers from North America during the onset of the 2009 pandemic demonstrates the central role of international air travel in virus migration. To characterize risk factors for pH1N1 transmission during air travel, we investigated travelers and airline employees from four North American flights carrying ill travelers with confirmed pH1N1 infection. Of 392 passengers and crew identified, information was available for 290 (74%) passengers were interviewed. Overall attack rates for acute respiratory infection and influenza-like illness 1–7 days after travel were 5.2% and 2.4% respectively. Of 43 individuals that provided sera, 4 (9.3%) tested positive for pH1N1 antibodies, including 3 with serologic evidence of asymptomatic infection. Investigation of novel influenza aboard aircraft may be instructive. However, beyond the initial outbreak phase, it may compete with community-based mitigation activities, and interpretation of findings will be difficult in the context of established community transmission. PMID:23523241

  4. Virus-like particles displaying H5, H7, H9 hemagglutinins and N1 neuraminidase elicit protective immunity to heterologous avian influenza viruses in chickens

    PubMed Central

    Pushko, Peter; Tretyakova, Irina; Hidajat, Rachmat; Zsak, Aniko; Chrzastek, Klaudia; Tumpey, Terrence M.; Kapczynski, Darrell R.

    2016-01-01

    Avian influenza (AI) viruses circulating in wild birds pose a serious threat to public health. Human and veterinary vaccines against AI subtypes are needed. Here we prepared triple-subtype VLPs that co-localized H5, H7 and H9 antigens derived from H5N1, H7N3 and H9N2 viruses. VLPs also contained influenza N1 neuraminidase and retroviral gag protein. The H5/H7/H9/N1/gag VLPs were prepared using baculovirus expression. Biochemical, functional and antigenic characteristics were determined including hemagglutination and neuraminidase enzyme activities. VLPs were further evaluated in a chicken AI challenge model for safety, immunogenicity and protective efficacy against heterologous AI viruses including H5N2, H7N3 and H9N2 subtypes. All vaccinated birds survived challenges with H5N2 and H7N3 highly pathogenic AI (HPAI) viruses, while all controls died. Immune response was also detectable after challenge with low pathogenicity AI (LPAI) H9N2 virus suggesting that H5/H7/H9/N1/gag VLPs represent a promising approach for the development of broadly protective AI vaccine. PMID:27936463

  5. Antigenic Patterns and Evolution of the Human Influenza A (H1N1) Virus

    PubMed Central

    Liu, Mi; Zhao, Xiang; Hua, Sha; Du, Xiangjun; Peng, Yousong; Li, Xiyan; Lan, Yu; Wang, Dayan; Wu, Aiping; Shu, Yuelong; Jiang, Taijiao

    2015-01-01

    The influenza A (H1N1) virus causes seasonal epidemics that result in severe illnesses and deaths almost every year. A deep understanding of the antigenic patterns and evolution of human influenza A (H1N1) virus is extremely important for its effective surveillance and prevention. Through development of antigenicity inference method for human influenza A (H1N1), named PREDAC-H1, we systematically mapped the antigenic patterns and evolution of the human influenza A (H1N1) virus. Eight dominant antigenic clusters have been inferred for seasonal H1N1 viruses since 1977, which demonstrated sequential replacements over time with a similar pattern in Asia, Europe and North America. Among them, six clusters emerged first in Asia. As for China, three of the eight antigenic clusters were detected in South China earlier than in North China, indicating the leading role of South China in H1N1 transmission. The comprehensive view of the antigenic evolution of human influenza A (H1N1) virus can help formulate better strategy for its prevention and control. PMID:26412348

  6. Virus-like particles displaying H5, H7, H9 hemagglutinins and N1 neuraminidase elicit protective immunity to heterologous avian influenza viruses in chickens

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Pushko, Peter, E-mail: ppushko@medigen-usa.com

    Avian influenza (AI) viruses circulating in wild birds pose a serious threat to public health. Human and veterinary vaccines against AI subtypes are needed. Here we prepared triple-subtype VLPs that co-localized H5, H7 and H9 antigens derived from H5N1, H7N3 and H9N2 viruses. VLPs also contained influenza N1 neuraminidase and retroviral gag protein. The H5/H7/H9/N1/gag VLPs were prepared using baculovirus expression. Biochemical, functional and antigenic characteristics were determined including hemagglutination and neuraminidase enzyme activities. VLPs were further evaluated in a chicken AI challenge model for safety, immunogenicity and protective efficacy against heterologous AI viruses including H5N2, H7N3 and H9N2 subtypes.more » All vaccinated birds survived challenges with H5N2 and H7N3 highly pathogenic AI (HPAI) viruses, while all controls died. Immune response was also detectable after challenge with low pathogenicity AI (LPAI) H9N2 virus suggesting that H5/H7/H9/N1/gag VLPs represent a promising approach for the development of broadly protective AI vaccine. - Highlights: •VLPs were prepared that co-localized H5, H7 and H9 subtypes in a VLP envelope. •VLPs were characterized including electron microscopy, HA assay and NA enzyme activity. •Experimental VLP vaccine was evaluated in an avian influenza challenge model. •VLPs induced immune responses against heterologous H5, H7 and H9 virus challenges.« less

  7. Induction of neutralising antibodies by virus-like particles harbouring surface proteins from highly pathogenic H5N1 and H7N1 influenza viruses

    PubMed Central

    Szécsi, Judit; Boson, Bertrand; Johnsson, Per; Dupeyrot-Lacas, Pia; Matrosovich, Mikhail; Klenk, Hans-Dieter; Klatzmann, David; Volchkov, Viktor; Cosset, François-Loïc

    2006-01-01

    There is an urgent need to develop novel approaches to vaccination against the emerging, highly pathogenic avian influenza viruses. Here, we engineered influenza viral-like particles (Flu-VLPs) derived from retroviral core particles that mimic the properties of the viral surface of two highly pathogenic influenza viruses of either H7N1 or H5N1 antigenic subtype. We demonstrate that, upon recovery of viral RNAs from a field strain, one can easily generate expression vectors that encode the HA, NA and M2 surface proteins of either virus and prepare high-titre Flu-VLPs. We characterise these Flu-VLPs incorporating the HA, NA and M2 proteins and we show that they induce high-titre neutralising antibodies in mice. PMID:16948862

  8. Construction and Immunogenicity Evaluation of Recombinant Influenza A Viruses Containing Chimeric Hemagglutinin Genes Derived from Genetically Divergent Influenza A H1N1 Subtype Viruses

    PubMed Central

    McCormick, Kara; Jiang, Zhiyong; Zhu, Longchao; Lawson, Steven R.; Langenhorst, Robert; Ransburgh, Russell; Brunick, Colin; Tracy, Miranda C.; Hurtig, Heather R.; Mabee, Leah M.; Mingo, Mark; Li, Yanhua; Webby, Richard J.

    2015-01-01

    Background and Objectives Influenza A viruses cause highly contagious diseases in a variety of hosts, including humans and pigs. To develop a vaccine that can be broadly effective against genetically divergent strains of the virus, in this study we employed molecular breeding (DNA shuffling) technology to create a panel of chimeric HA genes. Methods and Results Each chimeric HA gene contained genetic elements from parental swine influenza A viruses that had a history of zoonotic transmission, and also from a 2009 pandemic virus. Each parental virus represents a major phylogenetic clade of influenza A H1N1 viruses. Nine shuffled HA constructs were initially screened for immunogenicity in mice by DNA immunization, and one chimeric HA (HA-129) was expressed on both a A/Puerto Rico/8/34 backbone with mutations associated with a live, attenuated phenotype (PR8LAIV-129) and a A/swine/Texas/4199-2/98 backbone (TX98-129). When delivered to mice, the PR8LAIV-129 induced antibodies against all four parental viruses, which was similar to the breadth of immunity observed when HA-129 was delivered as a DNA vaccine. This chimeric HA was then tested as a candidate vaccine in a nursery pig model, using inactivated TX98-129 virus as the backbone. The results demonstrate that pigs immunized with HA-129 developed antibodies against all four parental viruses, as well as additional primary swine H1N1 influenza virus field isolates. Conclusion This study established a platform for creating novel genes of influenza viruses using a molecular breeding approach, which will have important applications toward future development of broadly protective influenza virus vaccines. PMID:26061265

  9. Antigenicity of the 2015–2016 seasonal H1N1 human influenza virus HA and NA proteins

    PubMed Central

    Anderson, Christopher S.; Wang, Jiong; Yang, Hongmei; Nogales, Aitor; Martinez-Sobrido, Luis; Zand, Martin S.; Sangster, Mark Y.; Topham, David J.

    2017-01-01

    Antigenic drift of the hemagglutinin (HA) and neuraminidase (NA) influenza virus proteins contributes to reduced vaccine efficacy. To analyze antigenic drift in human seasonal H1N1 viruses derived from the 2009 pandemic H1N1 virus (pH1N1-like viruses) accounts for the limited effectiveness (around 40%) of vaccination against pH1N1-like viruses during the 2015–2016 season, nasal washes/swabs collected from adult subjects in the Rochester, NY area, were used to sequence and isolate the circulating viruses. The HA and NA proteins from viruses circulating during the 2015–2016 season encoded eighteen and fourteen amino acid differences, respectively, when compared to A/California/04/2009, a strain circulating at the origin of the 2009 pandemic. The circulating strains belonged to subclade 6B.1, defined by HA amino acid substitutions S101N, S179N, and I233T. Hemagglutination-inhibiting (HAI) and HA-specific neutralizing serum antibody (Ab) titers from around 50% of pH1N1-like virus-infected subjects and immune ferrets were 2–4 fold lower for the 2015–2016 circulating strains compared to the vaccine strain. In addition, using a luminex-based mPlex HA assay, the binding of human sera from subjects infected with pH1N1-like viruses to the HA proteins from circulating and vaccine strains was not identical, strongly suggesting antigenic differences in the HA protein. Additionally, NA inhibition (NAI) Ab titers in human sera from pH1N1-like virus-infected subjects increased after the infection and there were measurable antigenic differences between the NA protein of circulating strains and the vaccine strain using both ferret and human antisera. Despite having been vaccinated, infected subjects exhibited low HAI Ab titers against the vaccine and circulating strains. This suggests that poor responses to the H1N1 component of the vaccine as well as antigenic differences in the HA and NA proteins of currently circulating pH1N1-like viruses could be contributing to risk of

  10. Domestic Ducks and H5N1 Influenza Epidemic, Thailand

    PubMed Central

    Songserm, Thaweesak; Jam-on, Rungroj; Sae-Heng, Numdee; Meemak, Noppadol; Hulse-Post, Diane J.; Sturm-Ramirez, Katharine M.

    2006-01-01

    In addition to causing 12 human deaths and 17 cases of human infection, the 2004 outbreak of H5N1 influenza virus in Thailand resulted in the death or slaughter of 60 million domestic fowl and the disruption of poultry production and trade. After domestic ducks were recognized as silent carriers of H5N1 influenza virus, government teams went into every village to cull flocks in which virus was detected; these team efforts markedly reduced H5N1 infection. Here we examine the pathobiology and epidemiology of H5N1 influenza virus in the 4 systems of duck raising used in Thailand in 2004. No influenza viruses were detected in ducks raised in "closed" houses with high biosecurity. However, H5N1 influenza virus was prevalent among ducks raised in "open" houses, free-ranging (grazing) ducks, and backyard ducks. PMID:16704804

  11. Influenza A (H1N1) virus pneumonia in intensive care unit.

    PubMed

    Adıgüzel, Nalan; Karakurt, Zuhal; Kalamanoğlu Balcı, Merih; Acartürk, Eylem; Güngör, Gökay; Yazıcıoğlu Moçin, Ozlem; Batı Kutlu, Semra; Yılmaz, Adnan

    2010-01-01

    Patients with influenza A (H1N1) virus infection have been admitted to intensive care units (ICU) due to development of severe respiratory failure. We described the clinical and epidemiologic characteristics of the 19 patients admitted to ICU due to influenza A (H1N1) virus infection. Study design is a descriptive case series in a third level-20 bed respiratory ICU at training hospital in Istanbul/Turkey. Influenza A (H1N1) virus infection was laboratory confirmed in specimens using real-time reverse transcriptase-polymerase-chain-reaction (RT-PCR). We collected data concerning demographic, epidemiologic and clinical characteristics of the patients, treatment mortality and outcome. From November 10 to December 31 2009, a total of 19 patients; 7 laboratory confirmed, 12 with high clinical suspicion were treated at ICU. Among 12 patients with high clinical suspicion; 3 patients had negative RT-PCR testing for influenza A (H1N1) virus, 9 patients had no tests. Mean age was 41.6 ± 11.9 (range 21 to 61). Median number of lung zone involvement was 4 (IQR= 3-4). Median PaO2/FiO2 was 105 (IQR= 85-165). Mean severity (APACHE II) and organ failure score (SOFA) were 13 ± 4 and 4.0 ± 1.3 respectively. Non-invasive mechanical ventilation (68.4%, n= 13), invasive mechanical ventilation (21.1%, n= 4) and nasal cannula oxygen (31.5%, n= 6) were implicated. The median length of ICU stay was 6 (IQR= 4-8). Oseltamivir therapy was given as 75 mg bid to 12 patients and 150 mg bid to 7 obese patients. ICU mortality rate was 21.1%. Presenting patients with pneumonia and acute respiratory failure due to influenza A (H1N1) virus infection were treated predominantly and successfully with non invasive mechanical ventilation. Clinicians should be aware of pulmonary complications of influenza A (H1N1) virus infection and that patients can be treated with non invasive mechanical ventilation paying attention to protective measures for health care providers.

  12. Antibody titer has positive predictive value for vaccine protection against challenge with natural antigenic-drift variants of H5N1 high-pathogenicity avian influenza viruses from Indonesia

    USDA-ARS?s Scientific Manuscript database

    Beginning with Hong Kong in 2002, vaccines have been used as part of an integrated control strategy in 14 countries/regions to protect poultry against H5N1 high pathogenicity avian influenza (HPAI). H5N1 HPAI was first reported in Indonesia in 2003 and vaccination was initiated the following year. ...

  13. Emergence of novel clade 2.3.4 influenza A (H5N1) virus subgroups in Yunnan Province, China.

    PubMed

    Hu, Tingsong; Song, Jianling; Zhang, Wendong; Zhao, Huanyun; Duan, Bofang; Liu, Qingliang; Zeng, Wei; Qiu, Wei; Chen, Gang; Zhang, Yingguo; Fan, Quanshui; Zhang, Fuqiang

    2015-07-01

    From December 2013 to March 2014, a major wave of highly pathogenic avian influenza outbreak occurred in poultry in Yunnan Province, China. We isolated and characterized eight highly pathogenic avian influenza A (H5N1) viruses from poultry. Full genome influenza sequences and analyses have been performed. Sequence analyses revealed that they belonged to clade 2.3.4 but did not fit within the three defined subclades. The isolated viruses were provisional subclade 2.3.4.4e. The provisional subclade 2.3.4.4e viruses with six internal genes from avian influenza A (H5N2) viruses in 2013 were the novel reassortant influenza A (H5N1) viruses which were associated with the outbreak of H5N1 occurred in egg chicken farms in Yunnan Province. The HA genes were similar to subtype H5 viruses isolated from January to March of 2014 in Asia including H5N6 and H5N8. The NA genes were most closely related to A/chicken/Vietnam/NCVD-KA423/2013 (H5N1) from the subclade 2.3.2. The HI assay demonstrated a lack of antigenic relatedness between clades 2.3.4.4e and 2.3.4.1 (RE-5 vaccine strain) or 2.3.2.2 (RE-6 vaccine strain). Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Predictors of self and parental vaccination decisions in England during the 2009 H1N1 pandemic: Analysis of the Flu Watch pandemic cohort data.

    PubMed

    Weston, Dale; Blackburn, Ruth; Potts, Henry W W; Hayward, Andrew C

    2017-07-05

    During the 2009 H1N1 pandemic, UK uptake of the pandemic influenza vaccine was very low. Furthermore, attitudes governing UK vaccination uptake during a pandemic are poorly characterised. To the best of our knowledge, there is no published research explicitly considering predictors of both adult self-vaccination and decisions regarding whether or not to vaccinate one's children among the UK population during the H1N1 pandemic. We therefore aimed to identify predictors of both self-vaccination decisions and parental vaccination decisions using data collected during the H1N1 pandemic as part of the Flu Watch cohort study. Data were analysed separately for 798 adults and 85 children: exploratory factor analysis facilitated reduction of 16 items on attitudes to pandemic vaccine into a smaller number of factors. Single variable analyses with vaccine uptake as the outcome were used to identify variables that were predictive of vaccination in children and adults. Potential predictors were: attitudinal factors created by data reduction, age group, sex, region, deprivation, ethnicity, chronic condition, vocation, healthcare-related occupation and previous influenza vaccination. Consistent with previous literature concerning adult self-vaccination decisions, we found that vaccine efficacy/safety and perceived risk of pandemic influenza were significant predictors of both self-vaccination decisions and parental vaccination decisions. This study provides the first systematic attempt to understand both the predictors of self and parental vaccination uptake among the UK general population during the H1N1 pandemic. Our findings indicate that concerns about vaccine safety, and vaccine effectiveness may be a barrier to increased uptake for both self and parental vaccination. Copyright © 2017. Published by Elsevier Ltd.

  15. Epidemiology of influenza in West Africa after the 2009 influenza A(H1N1) pandemic, 2010-2012.

    PubMed

    Talla Nzussouo, Ndahwouh; Duque, Jazmin; Adedeji, Adebayo Abel; Coulibaly, Daouda; Sow, Samba; Tarnagda, Zekiba; Maman, Issaka; Lagare, Adamou; Makaya, Sonia; Elkory, Mohamed Brahim; Kadjo Adje, Herve; Shilo, Paul Alhassan; Tamboura, Boubou; Cisse, Assana; Badziklou, Kossi; Maïnassara, Halima Boubacar; Bara, Ahmed Ould; Keita, Adama Mamby; Williams, Thelma; Moen, Ann; Widdowson, Marc-Alain; McMorrow, Meredith

    2017-12-04

    Over the last decade, capacity for influenza surveillance and research in West Africa has strengthened. Data from these surveillance systems showed influenza A(H1N1)pdm09 circulated in West Africa later than in other regions of the continent. We contacted 11 West African countries to collect information about their influenza surveillance systems (number of sites, type of surveillance, sampling strategy, populations sampled, case definitions used, number of specimens collected and number of specimens positive for influenza viruses) for the time period January 2010 through December 2012. Of the 11 countries contacted, 8 responded: Burkina Faso, Cote d'Ivoire, Mali, Mauritania, Niger, Nigeria, Sierra Leone and Togo. Countries used standard World Health Organization (WHO) case definitions for influenza-like illness (ILI) and severe acute respiratory illness (SARI) or slight variations thereof. There were 70 surveillance sites: 26 SARI and 44 ILI. Seven countries conducted SARI surveillance and collected 3114 specimens of which 209 (7%) were positive for influenza viruses. Among influenza-positive SARI patients, 132 (63%) were influenza A [68 influenza A(H1N1)pdm09, 64 influenza A(H3N2)] and 77 (37%) were influenza B. All eight countries conducted ILI surveillance and collected 20,375 specimens, of which 2278 (11%) were positive for influenza viruses. Among influenza-positive ILI patients, 1431 (63%) were influenza A [820 influenza A(H1N1)pdm09, 611 influenza A(H3N2)] and 847 (37%) were influenza B. A majority of SARI and ILI case-patients who tested positive for influenza (72% SARI and 59% ILI) were children aged 0-4 years, as were a majority of those enrolled in surveillance. The seasonality of influenza and the predominant influenza type or subtype varied by country and year. Influenza A(H1N1)pdm09 continued to circulate in West Africa along with influenza A(H3N2) and influenza B during 2010-2012. Although ILI surveillance systems produced a robust number of samples

  16. Potential antigenic explanation for atypical H1N1 infections among middle-aged adults during the 2013–2014 influenza season

    PubMed Central

    Linderman, Susanne L.; Chambers, Benjamin S.; Zost, Seth J.; Parkhouse, Kaela; Li, Yang; Herrmann, Christin; Ellebedy, Ali H.; Carter, Donald M.; Andrews, Sarah F.; Zheng, Nai-Ying; Huang, Min; Huang, Yunping; Strauss, Donna; Shaz, Beth H.; Hodinka, Richard L.; Reyes-Terán, Gustavo; Ross, Ted M.; Wilson, Patrick C.; Ahmed, Rafi; Bloom, Jesse D.; Hensley, Scott E.

    2014-01-01

    Influenza viruses typically cause the most severe disease in children and elderly individuals. However, H1N1 viruses disproportionately affected middle-aged adults during the 2013–2014 influenza season. Although H1N1 viruses recently acquired several mutations in the hemagglutinin (HA) glycoprotein, classic serological tests used by surveillance laboratories indicate that these mutations do not change antigenic properties of the virus. Here, we show that one of these mutations is located in a region of HA targeted by antibodies elicited in many middle-aged adults. We find that over 42% of individuals born between 1965 and 1979 possess antibodies that recognize this region of HA. Our findings offer a possible antigenic explanation of why middle-aged adults were highly susceptible to H1N1 viruses during the 2013–2014 influenza season. Our data further suggest that a drifted H1N1 strain should be included in future influenza vaccines to potentially reduce morbidity and mortality in this age group. PMID:25331901

  17. Academics and competing interests in H1N1 influenza media reporting.

    PubMed

    Mandeville, Kate L; O'Neill, Sam; Brighouse, Andrew; Walker, Alice; Yarrow, Kielan; Chan, Kenneth

    2014-03-01

    Concerns have been raised over competing interests (CoI) among academics during the 2009 to 2010 A/H1N1 pandemic. Media reporting can influence public anxiety and demand for pharmaceutical products. We assessed CoI of academics providing media commentary during the early stages of the pandemic. We performed a retrospective content analysis of UK newspaper articles on A/H1N1 influenza, examining quoted sources. We noted when academics made a risk assessment of the pandemic and compared this with official estimations. We also looked for promotion or rejection of the use of neuraminidase inhibitors or H1N1-specific vaccine. We independently searched for CoI for each academic. Academics were the second most frequently quoted source after Ministers of Health. Where both academics and official agencies estimated the risk of H1N1, one in two academics assessed the risk as higher than official predictions. For academics with CoI, the odds of a higher risk assessment were 5.8 times greater than those made by academics without CoI (Wald p value=0.009). One in two academics commenting on the use of neuraminidase inhibitors or vaccine had CoI. The odds of CoI in academics promoting the use of neuraminidase inhibitors were 8.4 times greater than for academics not commenting on their use (Fisher's exact p=0.005). There is evidence of CoI among academics providing media commentary during the early H1N1 pandemic. Heightened risk assessments, combined with advocacy for pharmaceutical products to counter this risk, may lead to increased public anxiety and demand. Academics should declare, and journalists report, relevant CoI for media interviews.

  18. Autoantibody response to adjuvant and nonadjuvant H1N1 vaccination in systemic lupus erythematosus.

    PubMed

    Urowitz, Murray B; Anton, Anoja; Ibanez, Dominique; Gladman, Dafna D

    2011-11-01

    It has been reported that influenza vaccination increases autoantibody production and/or disease activity in a significant proportion of patients with systemic lupus erythematosus (SLE). During the recent H1N1 epidemic, we investigated whether the use of adjuvant- and nonadjuvant-containing H1N1 vaccine induced increased autoantibody production in patients with SLE. Patients with SLE who received H1N1 vaccination and had a battery of 9 autoantibodies tested before and 1 and 3 months after vaccination were included. Antibodies tested included rheumatoid factor (nephelometry), antinuclear antibody (immunofluorescence), anti-DNA (Farr), anti-RNP, anti-Sm, anti-Ro, anti-La, anti-Scl-70, and anti-Jo-1 (enzyme-linked immunosorbent assay). Patients were evaluated by standard protocol, including items necessary to calculate the Systemic Lupus Erythematosus Disease Activity Index 2000 and the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index. Descriptive statistics and McNemar's test were performed to evaluate change in antibody positivity. Multivariate logistic regression was performed to adjust for repeated measures in the comparisons of autoantibodies over visits and vaccine types. One hundred three patients (94 women, 9 men) with a mean ± SD age at vaccination of 43.9 ± 15.2 years and a mean ± SD disease duration of 14.2 ± 11.0 years were included. Fifty-one patients received adjuvant and 52 received nonadjuvant vaccines. Antibody testing was performed a mean of 1.9 months prior to the vaccination. The first postvaccination sample was taken a mean of 1 month after vaccination and the second a mean of 3.5 months after vaccination. The percentage of patients with changes in antibodies following vaccination was not statistically significant for most antibodies. After adjusting for the number of tests performed, none of the associations was significant. H1N1 vaccination (both adjuvant and nonadjuvant) did not increase the

  19. Decreased Serologic Response in Vaccinated Military Recruits during 2011 Correspond to Genetic Drift in Concurrent Circulating Pandemic A/H1N1 Viruses

    PubMed Central

    Faix, Dennis J.; Hawksworth, Anthony W.; Myers, Christopher A.; Hansen, Christian J.; Ortiguerra, Ryan G.; Halpin, Rebecca; Wentworth, David; Pacha, Laura A.; Schwartz, Erica G.; Garcia, Shawn M. S.; Eick-Cost, Angelia A.; Clagett, Christopher D.; Khurana, Surender; Golding, Hana; Blair, Patrick J.

    2012-01-01

    Background Population-based febrile respiratory illness surveillance conducted by the Department of Defense contributes to an estimate of vaccine effectiveness. Between January and March 2011, 64 cases of 2009 A/H1N1 (pH1N1), including one fatality, were confirmed in immunized recruits at Fort Jackson, South Carolina, suggesting insufficient efficacy for the pH1N1 component of the live attenuated influenza vaccine (LAIV). Methodology/Principal Findings To test serologic protection, serum samples were collected at least 30 days post-vaccination from recruits at Fort Jackson (LAIV), Parris Island (LAIV and trivalent inactivated vaccine [TIV]) at Cape May, New Jersey (TIV) and responses measured against pre-vaccination sera. A subset of 78 LAIV and 64 TIV sera pairs from recruits who reported neither influenza vaccination in the prior year nor fever during training were tested by microneutralization (MN) and hemagglutination inhibition (HI) assays. MN results demonstrated that seroconversion in paired sera was greater in those who received TIV versus LAIV (74% and 37%). Additionally, the fold change associated with TIV vaccination was significantly different between circulating (2011) versus the vaccine strain (2009) of pH1N1 viruses (ANOVA p value = 0.0006). HI analyses revealed similar trends. Surface plasmon resonance (SPR) analysis revealed that the quantity, IgG/IgM ratios, and affinity of anti-HA antibodies were significantly greater in TIV vaccinees. Finally, sequence analysis of the HA1 gene in concurrent circulating 2011 pH1N1 isolates from Fort Jackson exhibited modest amino acid divergence from the vaccine strain. Conclusions/Significance Among military recruits in 2011, serum antibody response differed by vaccine type (LAIV vs. TIV) and pH1N1 virus year (2009 vs. 2011). We hypothesize that antigen drift in circulating pH1N1 viruses contributed to reduce vaccine effectiveness at Fort Jackson. Our findings have wider implications regarding vaccine

  20. Thromboembolic events in patients with severe pandemic influenza A/H1N1.

    PubMed

    Avnon, Lone Sølling; Munteanu, Daniela; Smoliakov, Alexander; Jotkowitz, Alan; Barski, Leonid

    2015-10-01

    The 2009 pandemic influenza A/H1N1 developed as a novel swine influenza which caused more diseases among younger age groups than in the elderly. Severe hypoxemic respiratory failure from A/H1N1 pneumonia resulted in an increased need for ICU beds. Several risk groups were identified that were at a higher risk for adverse outcomes. Pregnant women were a particularly vulnerable group of patients The CDC reported on the first ten patients with severe illness and acute hypoxemic respiratory failure associated with A/H1N1 infection, none of whom were pregnant, but they noticed that half of the patients had a pulmonary embolism. During a four-month period from September to December 2009, 252 patients were admitted to our hospital with confirmed pandemic influenza H1N1 by real-time reverse transcriptase-polymerase chain reaction test (rRT-PCR). We cared for twenty patients (7.9%) admitted to MICU with severe A/H1N1. Results on Thrombotic events were identified in five (25%) of our critically ill patients. We recommend that patients with severe influenza A/H1N1 pneumonitis and respiratory failure be administered DVT prophylaxis in particular if there are additional risk factors for TVE. Further prospective studies on the relationship of influenza A/H1N1 and VTE are needed. Copyright © 2015 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

  1. Clinical course of asthma patients with H1N1 influenza infection and oseltamivir.

    PubMed

    Kim, Min-Hye; Song, Woo-Jung; Yang, Min-Suk; Lee, So-Hee; Kwon, Jae-Woo; Kim, Sae-Hoon; Kang, Hye-Ryun; Park, Heung-Woo; Cho, Young-Joo; Cho, Sang-Heon; Min, Kyung-Up; Kim, You-Young; Chang, Yoon-Seok

    2018-02-01

    H1N1 influenza virus prevailed throughout the world in 2009. However, there are few reports on the clinical features of H1N1 influenza infection in adult asthma patients. We evaluated the clinical features in asthma patients with H1N1 influenza infection who took oseltamivir and compared them to those with other upper respiratory infections. We reviewed asthma patients over 15 years of age who had visited Seoul National University Hospital and Seoul National University Bundang Hospital for suspected H1N1 influenza infection from August 2009 to March 2010. Various clinical features such as hospital admission days, respiratory symptoms, basal lung function, and past history was compared between H1N1 influenza PCR positive and negative groups. A total of 111 asthmatics were enrolled. All patients took oseltamivir. H1N1 RT-PCR was positive in 62 patients (55.9%), negative in 49 patients (44.1%). Wheezing developed more frequently in the H1N1 positive group. (43.5 vs. 16.7%, P=0.044). The rate of acute asthma exacerbations and pneumonia development were higher in the H1N1 positive group (59.7 vs. 51%, P=0.015, 25.0% vs. 0%, P<0.001). The rates for emergency room visit, hospital admissions, intensive care unit admissions, hospital days were not different between the groups. Underlying medical conditions were accompanied more frequently in the H1N1 negative patients (21.6% vs. 30.6%, P=0.002), especially cardiac disease (7.2% vs. 15.3%, P=0.011). H1N1 influenza infection may affect the clinical course of asthma combined with more severe manifestations; however, Oseltamivir could have affected the clinical course of H1N1 infected patients and made it milder than expected.

  2. Broadly-reactive human monoclonal antibodies elicited following pandemic H1N1 influenza virus exposure protect mice from highly pathogenic H5N1 challenge.

    PubMed

    Nachbagauer, Raffael; Shore, David; Yang, Hua; Johnson, Scott K; Gabbard, Jon D; Tompkins, S Mark; Wrammert, Jens; Wilson, Patrick C; Stevens, James; Ahmed, Rafi; Krammer, Florian; Ellebedy, Ali H

    2018-06-13

    Broadly cross-reactive antibodies that recognize conserved epitopes within the influenza virus hemagglutinin (HA) stalk domain are of particular interest for their potential use as therapeutic and prophylactic agents against multiple influenza virus subtypes including zoonotic virus strains. Here, we characterized four human HA stalk-reactive monoclonal antibodies (mAbs) for their binding breadth and affinity, in vitro neutralization capacity, and in vivo protective potential against an highly pathogenic avian influenza virus. The monoclonal antibodies were isolated from individuals shortly following infection with (70-1F02 and 1009-3B05) or vaccination against (05-2G02 and 09-3A01) A(H1N1)pdm09. Three of the mAbs bound HAs from multiple strains of group 1 viruses, and one mAb, 05-2G02, bound to both group 1 and group 2 influenza A HAs. All four antibodies prophylactically protected mice against a lethal challenge with the highly pathogenic A/Vietnam/1203/04 (H5N1) strain. Two mAbs, 70-1F02 and 09-3A01, were further tested for their therapeutic efficacy against the same strain and showed good efficacy in this setting as well. One mAb, 70-1F02, was co-crystallized with H5 HA and showed similar heavy chain only interactions as a the previously described anti-stalk antibody CR6261. Finally, we showed that antibodies that compete with these mAbs are prevalent in serum from an individual recently infected with A(H1N1)pdm09 virus. The antibodies described here can be developed into broad-spectrum antiviral therapeutics that could be used to combat infections with zoonotic or emerging pandemic influenza viruses. IMPORTANCE The rise in zoonotic infections of humans with emerging influenza viruses is a worldwide public health concern. The majority of recent zoonotic human influenza cases were caused by H7N9 and H5Nx viruses and were associated with high morbidity and mortality. In addition, seasonal influenza viruses are estimated to cause up to 650,000 deaths annually

  3. Novel reassortant of swine influenza H1N2 virus in Germany.

    PubMed

    Zell, Roland; Motzke, Susann; Krumbholz, Andi; Wutzler, Peter; Herwig, Volker; Dürrwald, Ralf

    2008-01-01

    European porcine H1N2 influenza viruses arose after multiple reassortment steps involving a porcine influenza virus with avian-influenza-like internal segments and human H1N1 and H3N2 viruses in 1994. In Germany, H1N2 swine influenza viruses first appeared in 2000. Two German H1N2 swine influenza virus strains isolated from pigs with clinical symptoms of influenza are described. They were characterized by the neutralization test, haemagglutination inhibition (HI) test and complete sequencing of the viral genomes. The data demonstrate that these viruses represent a novel H1N2 reassortant. The viruses showed limited neutralization by sera raised against heterologous A/sw/Bakum/1,832/00-like H1N2 viruses. Sera pools from recovered pigs showed a considerably lower HI reaction, indicative of diagnostic difficulties in using the HI test to detect these viruses with A/sw/Bakum/1,832/00-like H1N2 antigens. Genome sequencing revealed the novel combination of the human-like HAH1 gene of European porcine H1N2 influenza viruses and the NAN2 gene of European porcine H3N2 viruses.

  4. Efficacy and safety of the H1N1 monovalent vaccine in renal-transplant recipients and dialysis patients.

    PubMed

    Beaudreuil, Séverine; Krivine, Anne; Hebibi, Hadia; Ducot, Béatrice; Mazet, Anne-Aurélie; Taouffik, Yacine; Seidowsky, Alexandre; Jacquet, Antoine; Lorenzo, Hans Kristian; Charpentier, Bernard; Francois, Hélène; Durrbach, Antoine

    2011-08-01

    The (H1N)1v influenza virus infection emerged in 2009 as a serious disease in targeted populations. Herein, we report on the tolerability and efficacy of (anti-H1N1)v vaccination in dialysis and transplant patients. 18 renal-transplant recipients (RTR) and 19 dialysis patients (DP) [12 patients treated with peritoneal dialysis (PDP), 7 patients treated with haemodialysis (HDP)] were enrolled. DPs received one monovalent H1N1 adjuvanted-vaccine injection, and RTRs received two unadjuvanted vaccine injections within a 21-day period. Serologic response was defined as a haemagglutination inhibition titre of > 40 (seroprotection) and/or at least a four-fold increase in antibody titre from baseline (seroconversion). Seroprotection rate after vaccination was greater in DPs than RTRs (p = 0.007), as was seroconversion (p = 0.001). Serologic response was similar in PDPs and HDPs. Serologic response was satisfactory in DPs, whichever dialysis mode (DPD or HDP). It was low in RTRs as compared to DPs.

  5. Complete Protection against Influenza Virus H1N1 Strain A/PR/8/34 Challenge in Mice Immunized with Non-Adjuvanted Novirhabdovirus Vaccines

    PubMed Central

    Rouxel, Ronan N.; Mérour, Emilie; Biacchesi, Stéphane; Brémont, Michel

    2016-01-01

    Novirhabdoviruses like Viral Hemorrhagic Septicemia Virus (VHSV) and Infectious Hematopoietic Necrosis Virus (IHNV) are fish-infecting Rhabdoviruses belonging to the Mononegavirales order. By reverse genetics, we previously showed that a recombinant VHSV expressing the West Nile Virus (WNV) E glycoprotein could serve as a vaccine platform against WNV. In the current study, we aimed to evaluate the potential of the Novirhabdovirus platform as a vaccine against influenza virus. Recombinant Novirhabdoviruses, rVHSV-HA and rIHNV-HA, expressing at the viral surface the hemagglutinin HA ectodomain were generated and used to immunized mice. We showed that mice immunized with either, rVHSV-HA or rIHNV-HA, elicited a strong neutralizing antibody response against influenza virus. A complete protection was conferred to the immunized mice when challenged with a lethal dose of influenza H1N1 A/PR/8/34 virus. Furthermore we showed that although acting as inert antigen in mice, since naturally inactivated over 20°C, mice immunized with rVHSV-HA or rIHNV-HA in the absence of adjuvant were also completely protected from a lethal challenge. Novirhabdoviruses platform are of particular interest as vaccines for mammals since they are cost effective to produce, relatively easy to generate and very effective to protect immunized animals. PMID:27711176

  6. H1N1 vaccines in a large observational cohort of patients with inflammatory bowel disease treated with immunomodulators and biological therapy.

    PubMed

    Rahier, Jean-François; Papay, Pavol; Salleron, Julia; Sebastian, Shaji; Marzo, Manuela; Peyrin-Biroulet, Laurent; Garcia-Sanchez, Valle; Fries, Walter; van Asseldonk, Dirk P; Farkas, Klaudia; de Boer, Nanne K; Sipponen, Taina; Ellul, Pierre; Louis, Edouard; Peake, Simon T C; Kopylov, Uri; Maul, Jochen; Makhoul, Badira; Fiorino, Gionata; Yazdanpanah, Yazdan; Chaparro, Maria

    2011-04-01

    Safety data are lacking on influenza vaccination in general and on A (H1N1)v vaccination in particular in patients with inflammatory bowel disease (IBD) receiving immmunomodulators and/or biological therapy. The authors conducted a multicentre observational cohort study to evaluate symptoms associated with influenza H1N1 adjuvanted (Pandemrix, Focetria, FluvalP) and non-adjuvanted (Celvapan) vaccines and to assess the risk of flare of IBD after vaccination. Patients with stable IBD treated with immunomodulators and/or biological therapy were recruited from November 2009 until March 2010 in 12 European countries. Harvey-Bradshaw Index and Partial Mayo Score were used to assess disease activity before and 4 weeks after vaccination in Crohn's disease (CD) and ulcerative colitis (UC). Vaccination-related events up to 7 days after vaccination were recorded. Of 575 patients enrolled (407 CD, 159 UC and nine indeterminate colitis; 53.9% female; mean age 40.3 years, SD 13.9), local and systemic symptoms were reported by 34.6% and 15.5% of patients, respectively. The most common local and systemic reactions were pain in 32.8% and fatigue in 6.1% of subjects. Local symptoms were more common with adjuvanted (39.3%) than non-adjuvanted (3.9%) vaccines (p < 0.0001), whereas rates of systemic symptoms were similar with both types (15.0% vs 18.4%, p = 0.44). Among the adjuvanted group, Pandemrix more often induced local reactions than FluvalP and Focetria (51.2% vs 27.6% and 15.4%, p < 0.0001). Solicited adverse events were not associated with any patient characteristics, specific immunomodulatory treatment, or biological therapy. Four weeks after vaccination, absence of flare was observed in 377 patients with CD (96.7%) and 151 with UC (95.6%). Influenza A (H1N1)v vaccines are well tolerated in patients with IBD. Non-adjuvanted vaccines are associated with fewer local reactions. The risk of IBD flare is probably not increased after H1N1 vaccination.

  7. Comprehensive Serological Analysis of Two Successive Heterologous Vaccines against H5N1 Avian Influenza Virus in Exotic Birds in Zoos▿

    PubMed Central

    Vergara-Alert, Júlia; Fernández-Bellon, Hugo; Busquets, Núria; Alcántara, Gabriel; Delclaux, María; Pizarro, Bienvenido; Sánchez, Celia; Sánchez, Azucena; Majó, Natàlia; Darji, Ayub

    2011-01-01

    In 2005, European Commission directive 2005/744/EC allowed controlled vaccination against avian influenza (AI) virus of valuable avian species housed in zoos. In 2006, 15 Spanish zoos and wildlife centers began a vaccination program with a commercial inactivated H5N9 vaccine. Between November 2007 and May 2008, birds from 10 of these centers were vaccinated again with a commercial inactivated H5N3 vaccine. During these campaigns, pre- and postvaccination samples from different bird orders were taken to study the response against AI virus H5 vaccines. Sera prior to vaccinations with both vaccines were examined for the presence of total antibodies against influenza A nucleoprotein (NP) by a commercial competitive enzyme-linked immunosorbent assay (cELISA). Humoral responses to vaccination were evaluated using a hemagglutination inhibition (HI) assay. In some taxonomic orders, both vaccines elicited comparatively high titers of HI antibodies against H5. Interestingly, some orders, such as Psittaciformes, which did not develop HI antibodies to either vaccine formulation when used alone, triggered notable HI antibody production, albeit in low HI titers, when primed with H5N9 and during subsequent boosting with the H5N3 vaccine. Vaccination with successive heterologous vaccines may represent the best alternative to widely protect valuable and/or endangered bird species against highly pathogenic AI virus infection. PMID:21430124

  8. Comprehensive serological analysis of two successive heterologous vaccines against H5N1 avian influenza virus in exotic birds in zoos.

    PubMed

    Vergara-Alert, Júlia; Fernández-Bellon, Hugo; Busquets, Núria; Alcántara, Gabriel; Delclaux, María; Pizarro, Bienvenido; Sánchez, Celia; Sánchez, Azucena; Majó, Natàlia; Darji, Ayub

    2011-05-01

    In 2005, European Commission directive 2005/744/EC allowed controlled vaccination against avian influenza (AI) virus of valuable avian species housed in zoos. In 2006, 15 Spanish zoos and wildlife centers began a vaccination program with a commercial inactivated H5N9 vaccine. Between November 2007 and May 2008, birds from 10 of these centers were vaccinated again with a commercial inactivated H5N3 vaccine. During these campaigns, pre- and postvaccination samples from different bird orders were taken to study the response against AI virus H5 vaccines. Sera prior to vaccinations with both vaccines were examined for the presence of total antibodies against influenza A nucleoprotein (NP) by a commercial competitive enzyme-linked immunosorbent assay (cELISA). Humoral responses to vaccination were evaluated using a hemagglutination inhibition (HI) assay. In some taxonomic orders, both vaccines elicited comparatively high titers of HI antibodies against H5. Interestingly, some orders, such as Psittaciformes, which did not develop HI antibodies to either vaccine formulation when used alone, triggered notable HI antibody production, albeit in low HI titers, when primed with H5N9 and during subsequent boosting with the H5N3 vaccine. Vaccination with successive heterologous vaccines may represent the best alternative to widely protect valuable and/or endangered bird species against highly pathogenic AI virus infection.

  9. Virus-like particles displaying H5, H7, H9 hemagglutinins and N1 neuraminidase elicit protective immunity to heterologous avian influenza viruses in chickens.

    PubMed

    Pushko, Peter; Tretyakova, Irina; Hidajat, Rachmat; Zsak, Aniko; Chrzastek, Klaudia; Tumpey, Terrence M; Kapczynski, Darrell R

    2017-01-15

    Avian influenza (AI) viruses circulating in wild birds pose a serious threat to public health. Human and veterinary vaccines against AI subtypes are needed. Here we prepared triple-subtype VLPs that co-localized H5, H7 and H9 antigens derived from H5N1, H7N3 and H9N2 viruses. VLPs also contained influenza N1 neuraminidase and retroviral gag protein. The H5/H7/H9/N1/gag VLPs were prepared using baculovirus expression. Biochemical, functional and antigenic characteristics were determined including hemagglutination and neuraminidase enzyme activities. VLPs were further evaluated in a chicken AI challenge model for safety, immunogenicity and protective efficacy against heterologous AI viruses including H5N2, H7N3 and H9N2 subtypes. All vaccinated birds survived challenges with H5N2 and H7N3 highly pathogenic AI (HPAI) viruses, while all controls died. Immune response was also detectable after challenge with low pathogenicity AI (LPAI) H9N2 virus suggesting that H5/H7/H9/N1/gag VLPs represent a promising approach for the development of broadly protective AI vaccine. Copyright © 2016. Published by Elsevier Inc.

  10. Generation and protective efficacy of a cold-adapted attenuated avian H9N2 influenza vaccine.

    PubMed

    Wei, Yandi; Qi, Lu; Gao, Huijie; Sun, Honglei; Pu, Juan; Sun, Yipeng; Liu, Jinhua

    2016-07-26

    To prevent H9N2 avian influenza virus infection in chickens, a long-term vaccination program using inactivated vaccines has been implemented in China. However, the protective efficacy of inactivated vaccines against antigenic drift variants is limited, and H9N2 influenza virus continues to circulate in vaccinated chicken flocks in China. Therefore, developing a cross-reactive vaccine to control the impact of H9N2 influenza in the poultry industry remains a high priority. In the present study, we developed a live cold-adapted H9N2 influenza vaccine candidate (SD/01/10-ca) by serial passages in embryonated eggs at successively lower temperatures. A total of 13 amino acid mutations occurred during the cold-adaptation of this H9N2 virus. The candidate was safe in chickens and induced robust hemagglutination-inhibition antibody responses and influenza virus-specific CD4(+) and CD8(+) T cell immune responses in chickens immunized intranasally. Importantly, the candidate could confer protection of chickens from homologous and heterogenous H9N2 viruses. These results demonstrated that the cold-adapted attenuated H9N2 virus would be selected as a vaccine to control the infection of prevalent H9N2 influenza viruses in chickens.

  11. Generation and protective efficacy of a cold-adapted attenuated avian H9N2 influenza vaccine

    PubMed Central

    Wei, Yandi; Qi, Lu; Gao, Huijie; Sun, Honglei; Pu, Juan; Sun, Yipeng; Liu, Jinhua

    2016-01-01

    To prevent H9N2 avian influenza virus infection in chickens, a long-term vaccination program using inactivated vaccines has been implemented in China. However, the protective efficacy of inactivated vaccines against antigenic drift variants is limited, and H9N2 influenza virus continues to circulate in vaccinated chicken flocks in China. Therefore, developing a cross-reactive vaccine to control the impact of H9N2 influenza in the poultry industry remains a high priority. In the present study, we developed a live cold-adapted H9N2 influenza vaccine candidate (SD/01/10-ca) by serial passages in embryonated eggs at successively lower temperatures. A total of 13 amino acid mutations occurred during the cold-adaptation of this H9N2 virus. The candidate was safe in chickens and induced robust hemagglutination-inhibition antibody responses and influenza virus–specific CD4+ and CD8+ T cell immune responses in chickens immunized intranasally. Importantly, the candidate could confer protection of chickens from homologous and heterogenous H9N2 viruses. These results demonstrated that the cold-adapted attenuated H9N2 virus would be selected as a vaccine to control the infection of prevalent H9N2 influenza viruses in chickens. PMID:27457755

  12. Cross reactivity of serum antibody responses elicited by DNA vaccines expressing HA antigens from H1N1 subtype influenza vaccines in the past 30 years.

    PubMed

    Almansour, Iman; Chen, Huaiqing; Wang, Shixia; Lu, Shan

    2013-10-01

    In the past three decades, ten H1 subtype influenza vaccines have been recommended for global seasonal flu vaccination. Some of them were used only for one year before being replaced by another H1 flu vaccine while others may be used for up to seven years. While the selection of a new seasonal flu vaccine was based on the escape of a new emerging virus that was not effectively protected by the existing flu formulation, there is limited information on the magnitude and breadth of cross reactivity among H1 subtype virus circulation over a long period. In the current study, HA-expressing DNA vaccines were constructed to express individual HA antigens from H1 subtype vaccines used in the past 30 y. Rabbits naïve to HA antibody responses were immunized with these HA DNA vaccines and the cross reactivity of these sera against HA antigen and related H1 viruses in the same period was studied. Our data indicate that the level of cross reactivity was different for different viral isolates and the key mutations responsible for the cross reactivity may involve only a limited number of residues. Our results provide useful information for the development of improved seasonal vaccines than can achieve broad protection against viruses within the same H1 subtype.

  13. [Pulmonary pathology in fatal human influenza A (H1N1) infection].

    PubMed

    Duan, Xue-jing; Li, Yong; Gong, En-cong; Wang, Jue; Lü, Fu-dong; Zhang, He-qiu; Sun, Lin; Yue, Zhu-jun; Song, Chen-chao; Zhang, Shi-Jie; Li, Ning; Dai, Jie

    2011-12-01

    To study the pulmonary pathology in patients died of fatal human influenza A(H1N1) infection. Eight cases of fatal human influenza A (H1N1) infection, including 2 autopsy cases and 6 paramortem needle puncture biopsies, were enrolled into the study. Histologic examination, immunohistochemitry, flow cytometry and Western blotting were carried out. The major pathologic changes included necrotizing bronchiolitis with surrounding inflammation, diffuse alveolar damage and pulmonary hemorrhage. Influenza viral antigen expression was detected in the lung tissue by Western blotting. Immunohistochemical study demonstrated the presence of nuclear protein and hemagglutinin virus antigens in parts of trachea, bronchial epithelium and glands, alveolar epithelium, macrophages and endothelium. Flow cytometry showed that the apoptotic rate of type II pneumocytes (32.15%, 78.15%) was significantly higher than that of the controls (1.93%, 3.77%). Necrotizing bronchiolitis, diffuse alveolar damage and pulmonary hemorrhage followed by pulmonary fibrosis in late stage are the major pathologic changes in fatal human influenza A (H1N1) infection.

  14. Antibody Titer Has Positive Predictive Value for Vaccine Protection against Challenge with Natural Antigenic-Drift Variants of H5N1 High-Pathogenicity Avian Influenza Viruses from Indonesia

    PubMed Central

    Suarez, David L.; Spackman, Erica; Jadhao, Samadhan; Dauphin, Gwenaelle; Kim-Torchetti, Mia; McGrane, James; Weaver, John; Daniels, Peter; Wong, Frank; Selleck, Paul; Wiyono, Agus; Indriani, Risa; Yupiana, Yuni; Sawitri Siregar, Elly; Prajitno, Teguh; Smith, Derek; Fouchier, Ron

    2015-01-01

    ABSTRACT Vaccines are used in integrated control strategies to protect poultry against H5N1 high-pathogenicity avian influenza (HPAI). H5N1 HPAI was first reported in Indonesia in 2003, and vaccination was initiated in 2004, but reports of vaccine failures began to emerge in mid-2005. This study investigated the role of Indonesian licensed vaccines, specific vaccine seed strains, and emerging variant field viruses as causes of vaccine failures. Eleven of 14 licensed vaccines contained the manufacturer's listed vaccine seed strains, but 3 vaccines contained a seed strain different from that listed on the label. Vaccines containing A/turkey/Wisconsin/1968 (WI/68), A/chicken/Mexico/28159-232/1994 (Mex/94), and A/turkey/England/N28/1973 seed strains had high serological potency in chickens (geometric mean hemagglutination inhibition [HI] titers, ≥1:169), but vaccines containing strain A/chicken/Guangdong/1/1996 generated by reverse genetics (rg; rgGD/96), A/chicken/Legok/2003 (Legok/03), A/chicken/Vietnam/C57/2004 generated by rg (rgVN/04), or A/chicken/Legok/2003 generated by rg (rgLegok/03) had lower serological potency (geometric mean HI titers, ≤1:95). In challenge studies, chickens immunized with any of the H5 avian influenza vaccines were protected against A/chicken/West Java/SMI-HAMD/2006 (SMI-HAMD/06) and were partially protected against A/chicken/Papua/TA5/2006 (Papua/06) but were not protected against A/chicken/West Java/PWT-WIJ/2006 (PWT/06). Experimental inactivated vaccines made with PWT/06 HPAI virus or rg-generated PWT/06 low-pathogenicity avian influenza (LPAI) virus seed strains protected chickens from lethal challenge, as did a combination of a commercially available live fowl poxvirus vaccine expressing the H5 influenza virus gene and inactivated Legok/03 vaccine. These studies indicate that antigenic variants did emerge in Indonesia following widespread H5 avian influenza vaccine usage, and efficacious inactivated vaccines can be developed using

  15. A duck enteritis virus-vectored bivalent live vaccine provides fast and complete protection against H5N1 avian influenza virus infection in ducks.

    PubMed

    Liu, Jinxiong; Chen, Pucheng; Jiang, Yongping; Wu, Li; Zeng, Xianying; Tian, Guobin; Ge, Jinying; Kawaoka, Yoshihiro; Bu, Zhigao; Chen, Hualan

    2011-11-01

    Ducks play an important role in the maintenance of highly pathogenic H5N1 avian influenza viruses (AIVs) in nature, and the successful control of AIVs in ducks has important implications for the eradication of the disease in poultry and its prevention in humans. The inactivated influenza vaccine is expensive, labor-intensive, and usually needs 2 to 3 weeks to induce protective immunity in ducks. Live attenuated duck enteritis virus (DEV; a herpesvirus) vaccine is used routinely to control lethal DEV infections in many duck-producing areas. Here, we first established a system to generate the DEV vaccine strain by using the transfection of overlapping fosmid DNAs. Using this system, we constructed two recombinant viruses, rDEV-ul41HA and rDEV-us78HA, in which the hemagglutinin (HA) gene of the H5N1 virus A/duck/Anhui/1/06 was inserted and stably maintained within the ul41 gene or between the us7 and us8 genes of the DEV genome. Duck studies indicated that rDEV-us78HA had protective efficacy similar to that of the live DEV vaccine against lethal DEV challenge; importantly, a single dose of 10(6) PFU of rDEV-us78HA induced complete protection against a lethal H5N1 virus challenge in as little as 3 days postvaccination. The protective efficacy against both lethal DEV and H5N1 challenge provided by rDEV-ul41HA inoculation in ducks was slightly weaker than that provided by rDEV-us78HA. These results demonstrate, for the first time, that recombinant DEV is suitable for use as a bivalent live attenuated vaccine, providing rapid protection against both DEV and H5N1 virus infection in ducks.

  16. Perspectives of Immunization Program Managers on 2009-10 H1N1 Vaccination in the United States: A National Survey

    PubMed Central

    Seib, Katherine; Wells, Katelyn; Hannan, Claire; Orenstein, Walter A.; Whitney, Ellen A. S.; Hinman, Alan R.; Berkelman, Ruth L.; Omer, Saad B.

    2012-01-01

    Abstract In June and July 2010, we conducted a national internet-based survey of 64 city, state, and territorial immunization program managers (IPMs) to assess their experiences in managing the 2009-10 H1N1 influenza vaccination campaign. Fifty-four (84%) of the managers or individuals responsible for an immunization program responded to the survey. To manage the campaign, 76% indicated their health department activated an incident command system (ICS) and 49% used an emergency operations center (EOC). Forty percent indicated they shared the leadership of the campaign with their state-level emergency preparedness program. The managers' perceptions of the helpfulness of the emergency preparedness staff was higher when they had collaborated with the emergency preparedness program on actual or simulated mass vaccination events within the previous 2 years. Fifty-seven percent found their pandemic influenza plan helpful, and those programs that mandated that vaccine providers enter data into their jurisdiction's immunization information system (IIS) were more likely than those who did not mandate data entry to rate their IIS as valuable for facilitating registration of nontraditional providers (42% vs. 25%, p<0.05) and tracking recalled influenza vaccine (50% vs. 38%, p<0.05). Results suggest that ICS and EOC structures, pandemic influenza plans, collaborations with emergency preparedness partners during nonemergencies, and expanded use of IIS can enhance immunization programs' ability to successfully manage a large-scale vaccination campaign. Maintaining the close working relationships developed between state-level immunization and emergency preparedness programs during the H1N1 influenza vaccination campaign will be especially important as states prepare for budget cuts in the coming years. PMID:22360580

  17. H5N1 influenza viruses: outbreaks and biological properties

    PubMed Central

    Neumann, Gabriele; Chen, Hualan; Gao, George F; Shu, Yuelong; Kawaoka, Yoshihiro

    2010-01-01

    All known subtypes of influenza A viruses are maintained in wild waterfowl, the natural reservoir of these viruses. Influenza A viruses are isolated from a variety of animal species with varying morbidity and mortality rates. More importantly, influenza A viruses cause respiratory disease in humans with potentially fatal outcome. Local or global outbreaks in humans are typically characterized by excess hospitalizations and deaths. In 1997, highly pathogenic avian influenza viruses of the H5N1 subtype emerged in Hong Kong that transmitted to humans, resulting in the first documented cases of human death by avian influenza virus infection. A new outbreak started in July 2003 in poultry in Vietnam, Indonesia, and Thailand, and highly pathogenic avian H5N1 influenza viruses have since spread throughout Asia and into Europe and Africa. These viruses continue to infect humans with a high mortality rate and cause worldwide concern of a looming pandemic. Moreover, H5N1 virus outbreaks have had devastating effects on the poultry industries throughout Asia. Since H5N1 virus outbreaks appear to originate from Southern China, we here examine H5N1 influenza viruses in China, with an emphasis on their biological properties. PMID:19884910

  18. Continual Reintroduction of Human Pandemic H1N1 Influenza A Viruses into Swine in the United States, 2009 to 2014

    PubMed Central

    Stratton, Jered; Killian, Mary Lea; Janas-Martindale, Alicia; Vincent, Amy L.

    2015-01-01

    ABSTRACT The diversity of influenza A viruses in swine (swIAVs) presents an important pandemic threat. Knowledge of the human-swine interface is particularly important for understanding how viruses with pandemic potential evolve in swine hosts. Through phylogenetic analysis of contemporary swIAVs in the United States, we demonstrate that human-to-swine transmission of pandemic H1N1 (pH1N1) viruses has occurred continuously in the years following the 2009 H1N1 pandemic and has been an important contributor to the genetic diversity of U.S. swIAVs. Although pandemic H1 and N1 segments had been largely removed from the U.S. swine population by 2013 via reassortment with other swIAVs, these antigens reemerged following multiple human-to-swine transmission events during the 2013-2014 seasonal epidemic. These findings indicate that the six internal gene segments from pH1N1 viruses are likely to be sustained long term in the U.S. swine population, with periodic reemergence of pandemic hemagglutinin (HA) and neuraminidase (NA) segments in association with seasonal pH1N1 epidemics in humans. Vaccinating U.S. swine workers may reduce infection of both humans and swine and in turn limit the role of humans as sources of influenza virus diversity in pigs. IMPORTANCE Swine are important hosts in the evolution of influenza A viruses with pandemic potential. Here, we analyze influenza virus sequence data generated by the U.S. Department of Agriculture's national surveillance system to identify the central role of humans in the reemergence of pandemic H1N1 (pH1N1) influenza viruses in U.S. swine herds in 2014. These findings emphasize the important role of humans as continuous sources of influenza virus diversity in swine and indicate that influenza viruses with pandemic HA and NA segments are likely to continue to reemerge in U.S. swine in association with seasonal pH1N1 epidemics in humans. PMID:25833052

  19. Continual Reintroduction of Human Pandemic H1N1 Influenza A Viruses into Swine in the United States, 2009 to 2014.

    PubMed

    Nelson, Martha I; Stratton, Jered; Killian, Mary Lea; Janas-Martindale, Alicia; Vincent, Amy L

    2015-06-01

    The diversity of influenza A viruses in swine (swIAVs) presents an important pandemic threat. Knowledge of the human-swine interface is particularly important for understanding how viruses with pandemic potential evolve in swine hosts. Through phylogenetic analysis of contemporary swIAVs in the United States, we demonstrate that human-to-swine transmission of pandemic H1N1 (pH1N1) viruses has occurred continuously in the years following the 2009 H1N1 pandemic and has been an important contributor to the genetic diversity of U.S. swIAVs. Although pandemic H1 and N1 segments had been largely removed from the U.S. swine population by 2013 via reassortment with other swIAVs, these antigens reemerged following multiple human-to-swine transmission events during the 2013-2014 seasonal epidemic. These findings indicate that the six internal gene segments from pH1N1 viruses are likely to be sustained long term in the U.S. swine population, with periodic reemergence of pandemic hemagglutinin (HA) and neuraminidase (NA) segments in association with seasonal pH1N1 epidemics in humans. Vaccinating U.S. swine workers may reduce infection of both humans and swine and in turn limit the role of humans as sources of influenza virus diversity in pigs. Swine are important hosts in the evolution of influenza A viruses with pandemic potential. Here, we analyze influenza virus sequence data generated by the U.S. Department of Agriculture's national surveillance system to identify the central role of humans in the reemergence of pandemic H1N1 (pH1N1) influenza viruses in U.S. swine herds in 2014. These findings emphasize the important role of humans as continuous sources of influenza virus diversity in swine and indicate that influenza viruses with pandemic HA and NA segments are likely to continue to reemerge in U.S. swine in association with seasonal pH1N1 epidemics in humans. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  20. Protective Efficacy of an H5N1 Inactivated Vaccine Against Challenge with Lethal H5N1, H5N2, H5N6, and H5N8 Influenza Viruses in Chickens.

    PubMed

    Zeng, Xianying; Chen, Pucheng; Liu, Liling; Deng, Guohua; Li, Yanbing; Shi, Jianzhong; Kong, Huihui; Feng, Huapeng; Bai, Jie; Li, Xin; Shi, Wenjun; Tian, Guobin; Chen, Hualan

    2016-05-01

    The Goose/Guangdong-lineage H5 viruses have evolved into diverse clades and subclades based on their hemagglutinin (HA) gene during their circulation in wild birds and poultry. Since late 2013, the clade 2.3.4.4 viruses have become widespread in poultry and wild bird populations around the world. Different subtypes of the clade 2.3.4.4 H5 viruses, including H5N1, H5N2, H5N6, and H5N8, have caused vast disease outbreaks in poultry in Asia, Europe, and North America. In this study, we developed a new H5N1 inactivated vaccine by using a seed virus (designated as Re-8) that contains the HA and NA genes from a clade 2.3.4.4 virus, A/chicken/Guizhou/4/13(H5N1) (CK/GZ/4/13), and its six internal genes from the high-growth A/Puerto Rico/8/1934 (H1N1) virus. We evaluated the protective efficacy of this vaccine in chickens challenged with one H5N1 clade 2.3.2.1b virus and six different subtypes of clade 2.3.4.4 viruses, including H5N1, H5N2, H5N6, and H5N8 strains. In the clade 2.3.2.1b virus DK/GX/S1017/13-challenged groups, half of the vaccinated chickens shed virus through the oropharynx and two birds (20%) died during the observation period. All of the control chickens shed viruses and died within 6 days of infection with challenge virus. All of the vaccinated chickens remained healthy following challenge with the six clade 2.3.4.4 viruses, and virus shedding was not detected from any of these birds; however, all of the control birds shed viruses and died within 4 days of challenge with the clade 2.3.4.4 viruses. Our results indicate that the Re-8 vaccine provides protection against different subtypes of clade 2.3.4.4 H5 viruses.

  1. Impact of vaccination on infection with Vietnam H5N1 high pathogenicity avian influenza virus in hens and the eggs they lay.

    PubMed

    Bertran, Kateri; Moresco, Kira; Swayne, David E

    2015-03-10

    High pathogenicity avian influenza virus (HPAIV) infections in chickens negatively impact egg production and cause egg contamination. Previously, vaccination maintained egg production and reduced egg contamination when challenged with a North American H5N2 HPAIV. However, Asian H5N1 HPAIV infection has some characteristics of increased pathogenicity compared to other H5 HPAIV such as more rapid drop and complete cessation in egg production. Sham (vaccinated at 25 and 28 weeks of age), inactivated H5N1 Once (1X-H5-Vax; vaccinated at 28 weeks of age only) and inactivated H5N1 Twice (2X-H5-Vax; vaccinated at 25 and 28 weeks of age) vaccinated adult White Leghorn hens were challenged intranasally at 31 weeks of age with 6.1 log10 mean embryo infectious doses (EID50) of clade 2.3.2.1a H5N1 HPAIV (A/chicken/Vietnam/NCVD-675/2011) which was homologous to the inactivated vaccine. Sham-vaccinated layers experienced 100% mortality within 3 days post-challenge; laid soft and thin-shelled eggs; had recovery of virus from oral swabs and in 53% of the eggs from eggshell surface (35%), yolk (24%), and albumin (41%); and had very high titers of virus (average 7.91 log10 EID50/g) in all segments of the oviduct and ovary. By comparison, 1X- and 2X-H5-Vax challenged hens survived infection, laid similar number of eggs pre- and post-challenge, all eggs had normal egg shell quality, and had significantly fewer contaminated eggs with reduced virus quantity. The 2X-H5-Vax hens had significantly higher HI titers by the day of challenge (304 GMT) and at termination (512 GMT) than 1X-H5-Vax hens (45 GMT and 128 GMT). The current study demonstrated that AIV infections caused by clade 2.3.2.1a H5N1 variants can be effectively controlled by either double or single homologous vaccination. Published by Elsevier Ltd.

  2. The emergence of influenza A H7N9 in human beings 16 years after influenza A H5N1: a tale of two cities.

    PubMed

    To, Kelvin K W; Chan, Jasper F W; Chen, Honglin; Li, Lanjuan; Yuen, Kwok-Yung

    2013-09-01

    Infection with either influenza A H5N1 virus in 1997 or avian influenza A H7N9 virus in 2013 caused severe pneumonia that did not respond to typical or atypical antimicrobial treatment, and resulted in high mortality. Both viruses are reassortants with internal genes derived from avian influenza A H9N2 viruses that circulate in Asian poultry. Both viruses have genetic markers of mammalian adaptation in their haemagglutinin and polymerase PB2 subunits, which enhanced binding to human-type receptors and improved replication in mammals, respectively. Hong Kong (affected by H5N1 in 1997) and Shanghai (affected by H7N9 in 2013) are two rapidly flourishing cosmopolitan megacities that were increasing in human population and poultry consumption before the outbreaks. Both cities are located along the avian migratory route at the Pearl River delta and Yangtze River delta. Whether the widespread use of the H5N1 vaccine in east Asia-with suboptimum biosecurity measures in live poultry markets and farms-predisposed to the emergence of H7N9 or other virus subtypes needs further investigation. Why H7N9 seems to be more readily transmitted from poultry to people than H5N1 is still unclear. Copyright © 2013 Elsevier Ltd. All rights reserved.

  3. Effect of a polysaccharide from Poria cocos on humoral response in mice immunized by H1N1 influenza and HBsAg vaccines.

    PubMed

    Wu, Yajun; Li, Shuai; Li, Haixia; Zhao, Chunzhi; Ma, Hao; Zhao, Xiunan; Wu, Junhua; Liu, Kunlu; Shan, Junjie; Wang, Yuxia

    2016-10-01

    Poria cocos has a long history of medicinal use in China. Polysaccharides and their derivatives in the medicine exhibit many beneficial biological activities including anticancer, anti-inflammatory, antioxidant and antiviral activities. In this study, a new polysaccharide (PCP-II) was isolated from sclerotium of Poria cocos. Its physico-chemical characters were identified and its adjuvant activity was investigated in mice co-immunized with H1N1 influenza vaccine and hepatitis B surface antigen (HBsAg). The results revealed that PCP-II has a molecular weight of 29.0kDa. It was composed of fucose, mannose, glucose and galactose in molar ration of 1.00:1.63:0.16:6.29 respectively. Pharmacological data demonstrated that PCP-II increased antigen-specific antibody levels in mice immunized with influenza vaccine. PCP-II also elicited anti-HBsAg antibodies at significantly higher titers and generated robust and durable immunity compared to mice immunized with HBsAg-alum following two administrations. PCP-II improved proliferation of splenocytes, stimulated IL-12p70 and TNF-α productions in dendritic cells and macrophages respectively. These results suggested that PCP-II-adjuvanted vaccines enhanced humoral and cellular immunity. PCP-II could be developed as an efficacious adjuvant in human and animal vaccines. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. H2N2 live attenuated influenza vaccine is safe and immunogenic for healthy adult volunteers

    PubMed Central

    Isakova-Sivak, Irina; Stukova, Marina; Erofeeva, Mariana; Naykhin, Anatoly; Donina, Svetlana; Petukhova, Galina; Kuznetsova, Victoria; Kiseleva, Irina; Smolonogina, Tatiana; Dubrovina, Irina; Pisareva, Maria; Nikiforova, Alexandra; Power, Maureen; Flores, Jorge; Rudenko, Larisa

    2015-01-01

    H2N2 influenza viruses have not circulated in the human population since 1968, but they are still being regularly detected in the animal reservoir, suggesting their high pandemic potential. To prepare for a possible H2N2 pandemic, a number of H2N2 vaccine candidates have been generated and tested in preclinical and clinical studies. Here we describe the results of a randomized, double-blind placebo-controlled phase 1 clinical trial of an H2N2 live attenuated influenza vaccine (LAIV) candidate prepared from a human influenza virus isolated in 1966. The vaccine candidate was safe and well-tolerated by healthy adults, and did not cause serious adverse events or an increased rate of moderate or severe reactogenicities. The H2N2 vaccine virus was infectious for Humans. It was shed by 78.6% and 74.1% volunteers after the first and second dose, respectively, most probably due to the human origin of the virus. Importantly, no vaccine virus transmission to unvaccinated subjects was detected during the study. We employed multiple immunological tests to ensure the adequate assessment of the H2N2 pandemic LAIV candidate and demonstrated that the majority (92.6%) of the vaccinated subjects responded to the H2N2 LAIV in one or more immunological tests, including 85.2% of subjects with antibody responses and 55.6% volunteers with cell-mediated immune responses. In addition, we observed strong correlation between the H2N2 LAIV virus replication in the upper respiratory tract and the development of antibody responses. PMID:25831405

  5. Evaluation of protective efficacy of three novel H3N2 canine influenza vaccines.

    PubMed

    Tu, Liqing; Zhou, Pei; Li, Lutao; Li, Xiuzhen; Hu, Renjun; Jia, Kun; Sun, Lingshuang; Yuan, Ziguo; Li, Shoujun

    2017-11-17

    Canine influenza virus (CIV) has the potential risk to spread in different areas and dog types. Thus, there is a growing need to develop an effective vaccine to control CIV disease. Here, we developed three vaccine candidates: 1) a recombinant pVAX1 vector expressing H3N2 CIV hemagglutinin (pVAX1-HA); 2) a live attenuated canine adenovirus type 2 expressing H3N2 CIV hemagglutinin (rCAV2-HA); and 3) an inactivated H3N2 CIV (A/canine/Guangdong/01/2006 (H3N2)). Mice received an initial intramuscular immunization that followed two booster injections at 2 and 4 weeks post-vaccination (wpv). The splenic lymphocytes were collected to assess the immune responses at 6 wpv. The protective efficacy was evaluated by challenging H3N2 CIV after vaccination (at 6 wpv). Our results demonstrated that all three vaccine candidates elicited cytokine and antibody responses in mice. The rCAV2-HA vaccine and the inactivated vaccine generated efficient protective efficacy in mice, whereas limited protection was provided by the pVAX1-HA DNA vaccine. Therefore, both the rCAV2-HA live recombinant virus and the inactivated CIV could be used as potential novel vaccines against H3N2CIV. This study provides guidance for choosing the most appropriate vaccine for the prevention and control of CIV disease.

  6. Mathematical Modeling of the Effectiveness of Facemasks in Reducing the Spread of Novel Influenza A (H1N1)

    PubMed Central

    Tracht, Samantha M.; Del Valle, Sara Y.; Hyman, James M.

    2010-01-01

    On June 11, 2009, the World Health Organization declared the outbreak of novel influenza A (H1N1) a pandemic. With limited supplies of antivirals and vaccines, countries and individuals are looking at other ways to reduce the spread of pandemic (H1N1) 2009, particularly options that are cost effective and relatively easy to implement. Recent experiences with the 2003 SARS and 2009 H1N1 epidemics have shown that people are willing to wear facemasks to protect themselves against infection; however, little research has been done to quantify the impact of using facemasks in reducing the spread of disease. We construct and analyze a mathematical model for a population in which some people wear facemasks during the pandemic and quantify impact of these masks on the spread of influenza. To estimate the parameter values used for the effectiveness of facemasks, we used available data from studies on N95 respirators and surgical facemasks. The results show that if N95 respirators are only 20% effective in reducing susceptibility and infectivity, only 10% of the population would have to wear them to reduce the number of influenza A (H1N1) cases by 20%. We can conclude from our model that, if worn properly, facemasks are an effective intervention strategy in reducing the spread of pandemic (H1N1) 2009. PMID:20161764

  7. From containment to community: Trigger points from the London pandemic (H1N1) 2009 influenza incident response.

    PubMed

    Balasegaram, S; Glasswell, A; Cleary, V; Turbitt, D; McCloskey, B

    2011-02-01

    In the UK, during the first wave of pandemic (H1N1) 2009 influenza, a national 'containment' strategy was employed from 25 April to 2 July 2009, with case finding, treatment of cases, contact tracing and prophylaxis of close contacts. The aim of the strategy was to delay the introduction and spread of pandemic flu in the UK, provide a better understanding of the course of the novel disease, and thereby allow more time for the development of treatment and vaccination options. Descriptive study of the management of the containment phase of pandemic (H1N1) 2009 influenza. Analysis of data reported to the London Flu Response Centre (LFRC). The average number of telephone calls and faxes per day from health professionals before 15 June 2009 was 188, but this started to rise from 363 on 12 June, to 674 on 15 June, and peaked on 22 June at 2206 calls. The number of cases confirmed [by pandemic (H1N1) 2009 influenza specific H1 and N1 polymerase chain reaction] in London rose to a peak of 200 cases per day. There were widespread school outbreaks reporting large numbers of absences with influenza-like illnesses. Activity in the LFRC intensified to a point where London was declared a 'hot spot' for pandemic (H1N1) 2009 influenza on 19 June 2009 because of sustained community transmission. The local incident response was modified to the 'outbreak management phase' of the containment phase. The sharp rise in the number of telephone calls and the rise in school outbreaks appeared to be trigger points for community transmission. These indicators should inform decisions on modifying public health strategy in pandemic situations. Copyright © 2010 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

  8. Effect of receptor binding specificity on the immunogenicity and protective efficacy of influenza virus A H1 vaccines

    PubMed Central

    Sun, Xiangjie; Cao, Weiping; Pappas, Claudia; Liu, Feng; Katz, Jacqueline M.; Tumpey, Terrence M.

    2018-01-01

    The biological basis for the poor immunogenicity of unadjuvanted avian influenza A virus vaccines in mammals is not well understood. Here, we mutated the hemagglutinin (HA) of two H1N1 virus vaccines to determine whether virus receptor binding specificity contributes to the low immunogenicity of avian influenza virus vaccines. Mutations were introduced into the HA of an avian influenza virus, A/Duck/New York/15024–21/96 (Dk/96) which switched the binding preference from α2,3- to α2,6-linked sialic acid (SA). A switch in receptor specificity of the human A/South Carolina/1/18 (SC/18) virus generated a mutant virus with α2,3 SA (avian) binding preference. Inactivated vaccines were generated and administered to mice and ferrets intramuscularly. We found that the vaccines with human receptor binding preference induced slightly higher antibody titers and cell-mediated immune responses compared to their isogenic viruses with avian receptor binding specificity. Upon challenge with DK/96 or SC18 virus, differences in lung virus titers between the vaccine groups with different receptor-binding specificities were minimal. Overall, our data suggest that receptor binding specificity contributes only marginally to the immunogenicity of avian influenza vaccines and that other factors may also be involved. PMID:25078114

  9. Protection of pigs against pandemic swine origin H1N1 influenza A virus infection by hemagglutinin- or neuraminidase-expressing attenuated pseudorabies virus recombinants.

    PubMed

    Klingbeil, Katharina; Lange, Elke; Blohm, Ulrike; Teifke, Jens P; Mettenleiter, Thomas C; Fuchs, Walter

    2015-03-02

    Influenza is an important respiratory disease of pigs, and may lead to novel human pathogens like the 2009 pandemic H1N1 swine-origin influenza virus (SoIV). Therefore, improved influenza vaccines for pigs are required. Recently, we demonstrated that single intranasal immunization with a hemagglutinin (HA)-expressing pseudorabies virus recombinant of vaccine strain Bartha (PrV-Ba) protected pigs from H1N1 SoIV challenge (Klingbeil et al., 2014). Now we investigated enhancement of efficacy by prime-boost vaccination and/or intramuscular administration. Furthermore, a novel PrV-Ba recombinant expressing codon-optimized N1 neuraminidase (NA) was included. In vitro replication of this virus was only slightly affected compared to parental virus. Unlike HA, the abundantly expressed NA was efficiently incorporated into PrV particles. Immunization of pigs with the two PrV recombinants, either singly or in combination, induced B cell proliferation and the expected SoIV-specific antibodies, whose titers increased substantially after boost vaccination. After immunization of animals with either PrV recombinant H1N1 SoIV challenge virus replication was significantly reduced compared to PrV-Ba vaccinated or naïve controls. Protective efficacy of HA-expressing PrV was higher than of NA-expressing PrV, and not significantly enhanced by combination. Despite higher serum antibody titers obtained after intramuscular immunization, transmission of challenge virus to naïve contact animals was only prevented after intranasal prime-boost vaccination with HA-expressing PrV-Ba. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. Kinetics of lung lesion development and pro-inflammatory cytokine response in pigs with vaccine-associated enhanced respiratory disease induced by challenge with pandemic (2009) A/H1N1 influenza virus.

    PubMed

    Gauger, P C; Vincent, A L; Loving, C L; Henningson, J N; Lager, K M; Janke, B H; Kehrli, M E; Roth, J A

    2012-11-01

    The objective of this report was to characterize the enhanced clinical disease and lung lesions observed in pigs vaccinated with inactivated H1N2 swine δ-cluster influenza A virus and challenged with pandemic 2009 A/H1N1 human influenza virus. Eighty-four, 6-week-old, cross-bred pigs were randomly allocated into 3 groups of 28 pigs to represent vaccinated/challenged (V/C), non-vaccinated/challenged (NV/C), and non-vaccinated/non-challenged (NV/NC) control groups. Pigs were intratracheally inoculated with pH1N1 and euthanized at 1, 2, 5, and 21 days post inoculation (dpi). Macroscopically, V/C pigs demonstrated greater percentages of pneumonia compared to NV/C pigs. Histologically, V/C pigs demonstrated severe bronchointerstitial pneumonia with necrotizing bronchiolitis accompanied by interlobular and alveolar edema and hemorrhage at 1 and 2 dpi. The magnitude of peribronchiolar lymphocytic cuffing was greater in V/C pigs by 5 dpi. Microscopic lung lesion scores were significantly higher in the V/C pigs at 2 and 5 dpi compared to NV/C and NV/NC pigs. Elevated TNF-α, IL-1β, IL-6, and IL-8 were detected in bronchoalveolar lavage fluid at all time points in V/C pigs compared to NV/C pigs. These data suggest H1 inactivated vaccines followed by heterologous challenge resulted in potentiated clinical signs and enhanced pulmonary lesions and correlated with an elevated proinflammatory cytokine response in the lung. The lung alterations and host immune response are consistent with the vaccine-associated enhanced respiratory disease (VAERD) clinical outcome observed reproducibly in this swine model.

  11. A bivalent live-attenuated influenza vaccine for the control and prevention of H3N8 and H3N2 canine influenza viruses.

    PubMed

    Rodriguez, Laura; Nogales, Aitor; Murcia, Pablo R; Parrish, Colin R; Martínez-Sobrido, Luis

    2017-08-03

    Canine influenza viruses (CIVs) cause a contagious respiratory disease in dogs. CIV subtypes include H3N8, which originated from the transfer of H3N8 equine influenza virus (EIV) to dogs; and the H3N2, which is an avian-origin virus adapted to infect dogs. Only inactivated influenza vaccines (IIVs) are currently available against the different CIV subtypes. However, the efficacy of these CIV IIVs is not optimal and improved vaccines are necessary for the efficient prevention of disease caused by CIVs in dogs. Since live-attenuated influenza vaccines (LAIVs) induce better immunogenicity and protection efficacy than IIVs, we have combined our previously described H3N8 and H3N2 CIV LAIVs to create a bivalent vaccine against both CIV subtypes. Our findings show that, in a mouse model of infection, the bivalent CIV LAIV is safe and able to induce, upon a single intranasal immunization, better protection than that induced by a bivalent CIV IIV against subsequent challenge with H3N8 or H3N2 CIVs. These protection results also correlated with the ability of the bivalent CIV LAIV to induce better humoral immune responses. This is the first description of a bivalent LAIV for the control and prevention of H3N8 and H3N2 CIV infections in dogs. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Anti-pandemic influenza A (H1N1) virus potential of catechin and gallic acid.

    PubMed

    You, Huey-Ling; Huang, Chao-Chun; Chen, Chung-Jen; Chang, Cheng-Chin; Liao, Pei-Lin; Huang, Sheng-Teng

    2018-05-01

    The pandemic influenza A (H1N1) virus has spread worldwide and infected a large proportion of the human population. Discovery of new and effective drugs for the treatment of influenza is a crucial issue for the global medical community. According to our previous study, TSL-1, a fraction of the aqueous extract from the tender leaf of Toonasinensis, has demonstrated antiviral activities against pandemic influenza A (H1N1) through the down-regulation of adhesion molecules and chemokine to prevent viral attachment. The aim of the present study was to identify the active compounds in TSL-1 which exert anti-influenza A (H1N1) virus effects. XTT assay was used to detect the cell viability. Meanwhile, the inhibitory effect on the pandemic influenza A (H1N1) virus was analyzed by observing plaque formation, qRT-PCR, neuraminidase activity, and immunofluorescence staining of influenza A-specific glycoprotein. Both catechin and gallic acid were found to be potent inhibitors in terms of influenza virus mRNA replication and MDCK plaque formation. Additionally, both compounds inhibited neuraminidase activities and viral glycoprotein. The 50% effective inhibition concentration (EC 50 ) of catechin and gallic acid for the influenza A (H1N1) virus were 18.4 μg/mL and 2.6 μg/mL, respectively; whereas the 50% cytotoxic concentrations (CC 50 ) of catechin and gallic acid were >100 μg/mL and 22.1 μg/mL, respectively. Thus, the selectivity indexes (SI) of catechin and gallic acid were >5.6 and 22.1, respectively. The present study demonstrates that catechin might be a safe reagent for long-term use to prevent influenza A (H1N1) virus infection; whereas gallic acid might be a sensitive reagent to inhibit influenza virus infection. We conclude that these two phyto-chemicals in TSL-1 are responsible for exerting anti-pandemic influenza A (H1N1) virus effects. Copyright © 2017. Published by Elsevier Taiwan LLC.

  13. Optimization of trypsins for influenza A/H1N1 virus replication in MDCK SI-6 cells, a novel MDCK cell line.

    PubMed

    Iskandar, Viska I; Sasaki, Yutaka; Yoshino, Naoto; Abubakar, Raden Z R; Sato, Shigehiro; Muraki, Yasushi

    2018-02-01

    A cell-based vaccine production method for influenza virus may be an effective and more rapid alternative to egg-based systems. For high-yield virus production, the effect of bovine, porcine, fungal, and recombinant trypsins on influenza A/H1N1 virus replication in MDCK SI-6 cells (SI-6 cells), a novel MDCK cell line developed by our research group, was examined. SI-6 cells infected with influenza A/H1N1 virus were incubated in the presence of four trypsin types at various concentrations, and virus yields in the culture medium were evaluated by a hemagglutination (HA) assay. Virus growth was most efficient in the presence of bovine and porcine trypsins. An analysis of the optimized concentration and definitive HA titer of each trypsin by Gaussian distribution revealed that comparable high virus yields (166.1 and 164.2 HAU/50μl) were obtained at the optimized concentrations of bovine (0.4μg/ml) and porcine (2.1μg/ml) trypsins, respectively, the yields of which were significantly higher than that of fungal and recombinant trypsins. We conclude that bovine and porcine trypsins are suitable for influenza A/H1N1 virus replication in SI-6 cells. This result complements our previous study and suggests the possible application of SI-6 cells to the development of cell-based influenza vaccines. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Safety and immunogenicity of a monovalent MF59®-adjuvanted A/H1N1 vaccine in HIV-infected children and young adults.

    PubMed

    Palma, Paolo; Romiti, Maria Luisa; Bernardi, Stefania; Pontrelli, Giuseppe; Mora, Nadia; Santilli, Veronica; Tchidjou, Hyppolite Kuekou; Aquilani, Angela; Cotugno, Nicola; Alghisi, Federico; Lucidi, Vincenzina; Rossi, Paolo; Douagi, Iyadh

    2012-03-01

    This Phase IV study evaluated the safety and immunogenicity of a two-dose, MF59®-adjuvanted (Novartis Vaccines, Marburg, Germany), monovalent, A/H1N1 pandemic influenza vaccination schedule in Human Immunodeficiency Virus (HIV) positive children and young adults. A total of 83 children infected with HIV-1, and 37 non-immunocompromised, age-matched controls were enrolled. All participants received two vaccine doses administered three weeks apart. Antibody responses were assessed by haemagglutination assay at baseline, three weeks after each vaccine dose, and six months after immunization. Vaccines were evaluated according to European influenza vaccine licensure criteria. The investigational vaccine was well tolerated. After the first vaccine dose, seroconversion rates were significantly lower in HIV-positive patients (60%) than controls (82%), with GMTs of 419 and 600, respectively. No significant differences in seroconversion rates were observed between the two study groups in response to the second vaccine dose. Persisting antibody titers were similar for both HIV-positive and non-infected controls, six months after immunization. One dose of MF59-adjuvanted vaccine was sufficient to provide adequate levels of seroprotection against A/H1N1 influenza disease in HIV-positive children. However, a two-dose vaccination schedule may be optimal for this population. Copyright © 2011 The International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.

  15. Global alert to avian influenza virus infection: From H5N1 to H7N9

    PubMed Central

    Poovorawan, Yong; Pyungporn, Sunchai; Prachayangprecha, Slinporn; Makkoch, Jarika

    2013-01-01

    Outbreak of a novel influenza virus is usually triggered by mutational change due to the process known as ‘antigenic shift’ or re-assortment process that allows animal-to-human or avian-to-human transmission. Birds are a natural reservoir for the influenza virus, and subtypes H5, H7, and H9 have all caused outbreaks of avian influenza in human populations. An especially notorious strain is the HPAI influenza virus H5N1, which has a mortality rate of approximately 60% and which has resulted in numerous hospitalizations, deaths, and significant economic loss. In March 2013, in Eastern China, there was an outbreak of the novel H7N9 influenza virus, which although less pathogenic in avian species, resulted in 131 confirmed cases and 36 deaths in humans over a two-month span. The rapid outbreak of this virus caused global concern but resulted in international cooperation to control the outbreak. Furthermore, cooperation led to valuable research-sharing including genome sequencing of the virus, the development of rapid and specific diagnosis, specimen sharing for future studies, and vaccine development. Although a H7N9 pandemic in the human population is possible due to its rapid transmissibility and extensive surveillance, the closure of the live-bird market will help mitigate the possibility of another H7N9 outbreak. In addition, further research into the source of the outbreak, pathogenicity of the virus, and the development of specific and sensitive detection assays will be essential for controlling and preparing for future H7N9 outbreaks. PMID:23916331

  16. Identification of influenza A pandemic (H1N1) 2009 variants during the first 2009 influenza outbreak in Mexico City.

    PubMed

    Zepeda, Hector M; Perea-Araujo, Lizbeth; Zarate-Segura, Paola B; Vázquez-Pérez, Joel A; Miliar-García, Angel; Garibay-Orijel, Claudio; Domínguez-López, Aarón; Badillo-Corona, Jesús A; López-Orduña, Eduardo; García-González, Octavio P; Villaseñor-Ruíz, Ignacio; Ahued-Ortega, Armando; Aguilar-Faisal, Leopoldo; Bravo, Jorge; Lara-Padilla, Eleazar; García-Cavazos, Ricardo J

    2010-05-01

    In March 2009, public health surveillance detected increased numbers of influenza-like illness presenting to hospitals in Mexico City. The aetiological agent was subsequently determined to be a novel influenza A (H1N1) triple reassortant, which has spread worldwide. As a consequence the World Health Organisation has declared the first Influenza pandemic of the 21st century. To describe clinically and molecularly the first outbreak of influenza A pH1N1 (2009) during 1-5 May to establish a baseline of epidemiological data for pH1N1. Also, to monitor for the emergence of antiviral resistance, and mutations affecting virulence and transmissibility. Samples were collected from 751 patients with influenza-like symptoms throughout Mexico City and were tested for influenza A pH1N1 (2009) using real-time PCR. In the samples that were positive for influenza A pH1N1 (2009) fragments from the haemagglutinin (H1) and neuraminidase (N1) genes were sequenced. A total of 203/751 (27%) patients were positive for the pandemic H1N1 (2009) virus (53% male and 47% female). The 0-12-year-old group was the most affected 85/751 (42%). Sequence analysis showed five new variants of the pandemic H1N1 (2009) virus for NA: G249E (GQ292900), M269I (GQ292892), Y274H (GQ292913), T332A (GQ292933), N344K (GQ292882), and four variants for HA: N461K (GQ293006), K505R (GQ292989), I435V (GQ292995), I527N (GQ292997). We have provided a baseline of epidemiological data from the first outbreak of influenza A pH1N1 (2009) during 1-5 May in Mexico City. The sequencing of partial fragments of the HA and NA genes did not show the presence of previously described mutations affecting known sites of antiviral resistance in seasonal influenza A such as the H275Y (oseltamivir resistance), R293 or N295 etc. Copyright 2010 Elsevier B.V. All rights reserved.

  17. Influenza A(H1N1)v in Germany: the first 10,000 cases.

    PubMed

    Gilsdorf, Andreas; Poggensee, Gabriele

    2009-08-27

    The analysis of the first 10,000 cases of influenza A(H1N1)v in Germany confirms findings from other sources that the virus is currently mainly causing mild diseases, affecting mostly adolescents and young adults. Overall hospitalisation rate for influenza A(H1N1)v was low (7%). Only 3% of the cases had underlying conditions and pneumonia was rare (0.4%). Both reporting and testing requirements have been adapted recently, taking into consideration the additional information available on influenza A(H1N1)v infections.

  18. 'Out of two bad choices, I took the slightly better one': vaccination dilemmas for Scottish and Polish migrant women during the H1N1 influenza pandemic.

    PubMed

    Sim, J A; Ulanika, A A; Katikireddi, S V; Gorman, D

    2011-08-01

    Pregnancy has been identified as a risk factor for complications from pandemic H1N1 influenza, and pregnant women were identified as a target group for vaccination in the UK in the 2009 pandemic. Poland took a more conservative approach, and did not offer vaccination to pregnant women. Poland accounts for the largest wave of recent migrants to the UK, many of whom are in their reproductive years and continue to participate actively in Polish healthcare systems after migration. The authors speculated that different national responses may shape differences in approaches to the vaccine between Scottish and Polish women. This study therefore aimed to assess how pregnant Polish migrants to Scotland weighed up the risks and benefits of the vaccine for pandemic H1N1 influenza in comparison with their Scottish counterparts. A qualitative interview-based study comparing the views of Scottish and Polish pregnant women on H1N1 vaccination was carried out in 'real time' during the first 2 weeks of the vaccination programme in November 2009. One-to-one interviews were conducted with 10 women (five Polish and five Scottish) in their native language. Interviews were transcribed, translated, coded and analysed for differences and similarities in decision-making processes between the two groups. Contrary to expectations, Scottish and Polish women drew on a strikingly similar set of considerations in deciding whether or not to accept the vaccine, with individual women reaching different conclusions. Almost all of the women adopted a critical stance towards the vaccine. While most women understood that pregnancy was a risk factor for complications from influenza, their primary concern was protecting family health overall and their fetus in particular. Deciding whether or not to accept the vaccine was difficult for women. Some identified a contradiction between the culture of caution which characterizes pregnancy-related advice, and the fact that they were being urged to accept what

  19. Inactivation of influenza A virus H1N1 by disinfection process.

    PubMed

    Jeong, Eun Kyo; Bae, Jung Eun; Kim, In Seop

    2010-06-01

    Because any patient, health care worker, or visitor is capable of transmitting influenza to susceptible persons within hospitals, hospital-acquired influenza has been a clinical concern. Disinfection and cleaning of medical equipment, surgical instruments, and hospital environment are important measures to prevent transmission of influenza virus from hospitals to individuals. This study was conducted to evaluate the efficacy of disinfection processes, which can be easily operated at hospitals, in inactivating influenza A virus H1N1 (H1N1). The effects of 0.1 mol/L NaOH, 70% ethanol, 70% 1-propanol, solvent/detergent (S/D) using 0.3% tri (n-butyl)-phosphate and 1.0% Triton X-100, heat, and ethylene oxide (EO) treatments in inactivating H1N1 were determined. Inactivation of H1N1 was kinetically determined by the treatment of disinfectants to virus solution. Also, a surface test method, which involved drying an amount of virus on a surface and then applying the inactivation methods for 1 minute of contact time, was used to determine the virucidal activity. H1N1 was completely inactivated to undetectable levels in 1 minute of 70% ethanol, 70% 1-propanol, and solvent/detergent treatments in the surface tests as well as in the suspension tests. H1N1 was completely inactivated in 1 minute of 0.1 mol/L NaOH treatment in the suspension tests and also effectively inactivated in the surface tests with the log reduction factor of 3.7. H1N1 was inactivated to undetectable levels within 5 minutes, 2.5 minutes, and 1 minute of heat treatment at 70, 80, and 90 degrees C, respectively in the suspension tests. Also, H1N1 was completely inactivated by EO treatment in the surface tests. Common disinfectants, heat, and EO tested in this study were effective at inactivating H1N1. These results would be helpful in implementing effective disinfecting measures to prevent hospital-acquired infections. Copyright 2010 Association for Professionals in Infection Control and Epidemiology, Inc

  20. Spatiotemporal dynamics of influenza A(H1N1)pdm09 in Brazil during the pandemic and post-pandemic periods.

    PubMed

    Manito, Alessandra C B; Gräf, Tiago; Lunge, Vagner R; Ikuta, Nilo

    2017-06-15

    Influenza A(H1N1)pdm09 was responsible for the first global flu pandemic in 21st century affecting all the world. In Brazil, A(H1N1)pdm09 is still circulating as a seasonal virus, causing deaths every year. Nevertheless, the viral diffusion process that yearly seeds new influenza strains in the country was not investigated yet. The aim of the current study was to describe the phylodynamics and phylogeography of influenza A(H1N1)pdm09 in Brazil between 2009 and 2014. Neuraminidase sequences from Brazil and other regions of the World were retrieved and analyzed. Bayesian phylogeographic and phylodynamic model approaches were used to reconstruct the spatiotemporal and demographic history of influenza A(H1N1)pdm09 in Brazil (divided in subtropical and tropical regions) and related countries. Our analyses reveal that new influenza A(H1N1)pdm09 lineages are seeded in Brazil in almost each year and the main sources of viral diversity are North America, Europe and East Asia. The phylogeographic asymmetric model also revealed that Brazil, mainly the subtropical region, seeds viral lineages into other countries. Coalescent analysis of the compiled dataset reconstructed the peak of viral transmissions in the winter months of Southern hemisphere. The results presented in this study can be informative to public health, guide intervention strategies and in the understanding of flu virus migration, which helps to predict antigenic drift and consequently the developing of new vaccines. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Comparison of patients with avian influenza A (H7N9) and influenza A (H1N1) complicated by acute respiratory distress syndrome.

    PubMed

    Li, Hongyan; Weng, Heng; Lan, Changqing; Zhang, Hongying; Wang, Xinhang; Pan, Jianguang; Chen, Lulu; Huang, Jinbao

    2018-03-01

    The aim of this study was to compare the clinical features of patients with avian influenza A (H7N9) and influenza A (H1N1) complicated by acute respiratory distress syndrome (ARDS).The clinical data of 18 cases of H7N9 and 26 cases of H1N1 with ARDS were collected and compared in the respiratory intensive care unit (RICU) of Fuzhou Pulmonary Hospital of Fujian from March 2014 to December 2016.Patients with H7N9 had a higher acute physiology and chronic health evaluation-II score (P < .05) and lung injury score (P < .05). The rates of coexisting diabetes mellitus, hyperpyrexia, and bloody sputum production were significantly higher in the H7N9 group than in the H1N1 group (P < .05). The H7N9 group had a longer duration of viral shedding from the onset of illness (P < .05) and from the initiation of antiviral therapy (P < .05) to a negative viral test result than the H1N1 group. Patients with H7N9 had higher rates of invasive mechanical ventilation; serious complications, including alimentary tract hemorrhage, pneumothorax or septum emphysema, hospital-acquired pneumonia (HAP) and multiple organ dysfunction syndrome (MODS); and hospital mortality (P < .05). At the 6th month of follow-up, the rates of bronchiectasia, reticular opacities, fibrous stripes, and patchy opacities on chest computed tomography (CT) were significantly higher in the H7N9 group than in the H1N1 group (P < .05). Based on multiple logistic regression analysis, H7N9 influenza viral infection was associated with a higher risk of the presence of severe ARDS than H1N1 influenza viral infection (odds ratio 8.29, 95% confidence interval [CI] 1.53-44.94; P < .05).Compared to patients with H1N1, patients with H7N9 complicated by ARDS had much more severe disease. During long-term follow-up, more changes in pulmonary fibrosis were observed in patients with H7N9 than in patients with H1N1 during the convalescent stage.

  2. A single vaccination of commercial broilers does not reduce transmission of H5N1 highly pathogenic avian influenza

    PubMed Central

    2011-01-01

    Vaccination of chickens has become routine practice in Asian countries in which H5N1 highly pathogenic avian influenza (HPAI) is endemically present. This mainly applies to layer and breeder flocks, but broilers are usually left unvaccinated. Here we investigate whether vaccination is able to reduce HPAI H5N1 virus transmission among broiler chickens. Four sets of experiments were carried out, each consisting of 22 replicate trials containing a pair of birds. Experiments 1-3 were carried out with four-week-old birds that were unvaccinated, and vaccinated at day 1 or at day 10 of age. Experiment 4 was carried out with unvaccinated day-old broiler chicks. One chicken in each trial was inoculated with H5N1 HPAI virus. One chicken in each trial was inoculated with virus. The course of the infection chain was monitored by serological analysis, and by virus isolation performed on tracheal and cloacal swabs. The analyses were based on a stochastic SEIR model using a Bayesian inferential framework. When inoculation was carried out at the 28th day of life, transmission was efficient in unvaccinated birds, and in birds vaccinated at first or tenth day of life. In these experiments estimates of the latent period (~1.0 day), infectious period (~3.3 days), and transmission rate parameter (~1.4 per day) were similar, as were estimates of the reproduction number (~4) and generation interval (~1.4 day). Transmission was significantly less efficient in unvaccinated chickens when inoculation was carried out on the first day of life. These results show that vaccination of broiler chickens does not reduce transmission, and suggest that this may be due to the interference of maternal immunity. PMID:21635732

  3. Oseltamivir-Resistant Influenza Virus A (H1N1), Europe, 2007–08 Season

    PubMed Central

    Lackenby, Angie; Hungnes, Olav; Lina, Bruno; van der Werf, Sylvie; Schweiger, Brunhilde; Opp, Matthias; Paget, John; van de Kassteele, Jan; Hay, Alan; Zambon, Maria

    2009-01-01

    In Europe, the 2007–08 winter season was dominated by influenza virus A (H1N1) circulation through week 7, followed by influenza B virus from week 8 onward. Oseltamivir-resistant influenza viruses A (H1N1) (ORVs) with H275Y mutation in the neuraminidase emerged independently of drug use. By country, the proportion of ORVs ranged from 0% to 68%, with the highest proportion in Norway. The average weighted prevalence of ORVs across Europe increased gradually over time, from near 0 in week 40 of 2007 to 56% in week 19 of 2008 (mean 20%). Neuraminidase genes of ORVs possessing the H275Y substitution formed a homogeneous subgroup closely related to, but distinguishable from, those of oseltamivir-sensitive influenza viruses A (H1N1). Minor variants of ORVs emerged independently, indicating multiclonal ORVs. Overall, the clinical effect of ORVs in Europe, measured by influenza-like illness or acute respiratory infection, was unremarkable and consistent with normal seasonal activity. PMID:19331731

  4. Immunization of pigs with an attenuated pseudorabies virus recombinant expressing the haemagglutinin of pandemic swine origin H1N1 influenza A virus.

    PubMed

    Klingbeil, Katharina; Lange, Elke; Teifke, Jens P; Mettenleiter, Thomas C; Fuchs, Walter

    2014-04-01

    Pigs can be severely harmed by influenza, and represent important reservoir hosts, in which new human pathogens such as the recent pandemic swine-origin H1N1 influenza A virus can arise by mutation and reassortment of genome segments. To obtain novel, safe influenza vaccines for pigs, and to investigate the antigen-specific immune response, we modified an established live-virus vaccine against Aujeszky's disease of swine, pseudorabies virus (PrV) strain Bartha (PrV-Ba), to serve as vector for the expression of haemagglutinin (HA) of swine-origin H1N1 virus. To facilitate transgene insertion, the genome of PrV-Ba was cloned as a bacterial artificial chromosome. HA expression occurred under control of the human or murine cytomegalovirus immediate early promoters (P-HCMV, P-MCMV), but could be substantially enhanced by synthetic introns and adaptation of the codon usage to that of PrV. However, despite abundant expression, the heterologous glycoprotein was not detectably incorporated into mature PrV particles. Replication of HA-expressing PrV in cell culture was only slightly affected compared to that of the parental virus strain. A single immunization of pigs with the PrV vector expressing the codon-optimized HA gene under control of P-MCMV induced high levels of HA-specific antibodies. The vaccinated animals were protected from clinical signs after challenge with a related swine-origin H1N1 influenza A virus, and challenge virus shedding was significantly reduced.

  5. Swine influenza virus vaccine serologic cross-reactivity to contemporary US swine H3N2 and efficacy in pigs infected with an H3N2 similar to 2011-2012 H3N2v.

    PubMed

    Kitikoon, Pravina; Gauger, Phillip C; Anderson, Tavis K; Culhane, Marie R; Swenson, Sabrina; Loving, Crystal L; Perez, Daniel R; Vincent, Amy L

    2013-12-01

    Swine influenza A virus (IAV) reassortment with 2009 H1N1 pandemic (H1N1pdm09) virus has been documented, and new genotypes and subclusters of H3N2 have since expanded in the US swine population. An H3N2 variant (H3N2v) virus with the H1N1pdm09 matrix gene and the remaining genes of swine triple reassortant H3N2 caused outbreaks at agricultural fairs in 2011-2012. To assess commercial swine IAV vaccines' efficacy against H3N2 viruses, including those similar to H3N2v, antisera to three vaccines were tested by hemagglutinin inhibition (HI) assay against contemporary H3N2. Vaccine 1, with high HI cross-reactivity, was further investigated for efficacy against H3N2 virus infection in pigs with or without maternally derived antibodies (MDA). In addition, efficacy of a vaccine derived from whole inactivated virus (WIV) was compared with live attenuated influenza virus (LAIV) against H3N2. Hemagglutinin inhibition cross-reactivity demonstrated that contemporary swine H3N2 viruses have drifted from viruses in current swine IAV vaccines. The vaccine with the highest level of HI cross-reactivity significantly protected pigs without MDA. However, the presence of MDA at vaccination blocked vaccine efficacy. The performance of WIV and LAIV was comparable in the absence of MDA. Swine IAV in the United States is complex and dynamic. Vaccination to minimize virus shedding can help limit transmission of virus among pigs and people. However, vaccines must be updated. A critical review of the use of WIV in sows is required in the context of the current IAV ecology and vaccine application in pigs with MDA. Published 2013. This article is a U.S. Government work and is in the public domain in the USA.

  6. Diversifying Selection Analysis Predicts Antigenic Evolution of 2009 Pandemic H1N1 Influenza A Virus in Humans.

    PubMed

    Lee, Alexandra J; Das, Suman R; Wang, Wei; Fitzgerald, Theresa; Pickett, Brett E; Aevermann, Brian D; Topham, David J; Falsey, Ann R; Scheuermann, Richard H

    2015-05-01

    Although a large number of immune epitopes have been identified in the influenza A virus (IAV) hemagglutinin (HA) protein using various experimental systems, it is unclear which are involved in protective immunity to natural infection in humans. We developed a data mining approach analyzing natural H1N1 human isolates to identify HA protein regions that may be targeted by the human immune system and can predict the evolution of IAV. We identified 16 amino acid sites experiencing diversifying selection during the evolution of prepandemic seasonal H1N1 strains and found that 11 sites were located in experimentally determined B-cell/antibody (Ab) epitopes, including three distinct neutralizing Caton epitopes: Sa, Sb, and Ca2 [A. J. Caton, G. G. Brownlee, J. W. Yewdell, and W. Gerhard, Cell 31:417-427, 1982, http://dx.doi.org/10.1016/0092-8674(82)90135-0]. We predicted that these diversified epitope regions would be the targets of mutation as the 2009 H1N1 pandemic (pH1N1) lineage evolves in response to the development of population-level protective immunity in humans. Using a chi-squared goodness-of-fit test, we identified 10 amino acid sites that significantly differed between the pH1N1 isolates and isolates from the recent 2012-2013 and 2013-2014 influenza seasons. Three of these sites were located in the same diversified B-cell/Ab epitope regions as identified in the analysis of prepandemic sequences, including Sa and Sb. As predicted, hemagglutination inhibition (HI) assays using human sera from subjects vaccinated with the initial pH1N1 isolate demonstrated reduced reactivity against 2013-2014 isolates. Taken together, these results suggest that diversifying selection analysis can identify key immune epitopes responsible for protective immunity to influenza virus in humans and thereby predict virus evolution. The WHO estimates that approximately 5 to 10% of adults and 20 to 30% of children in the world are infected by influenza virus each year. While an adaptive

  7. High conservation level of CD8(+) T cell immunogenic regions within an unusual H1N2 human influenza variant.

    PubMed

    Komadina, Naomi; Quiñones-Parra, Sergio M; Kedzierska, Katherine; McCaw, James M; Kelso, Anne; Leder, Karin; McVernon, Jodie

    2016-10-01

    Current seasonal influenza vaccines require regular updates due to antigenic drift causing loss of effectiveness and therefore providing little or no protection against novel influenza A subtypes. Next generation vaccines capable of eliciting CD8(+) T cell (CTL) mediated cross-protective immunity may offer a long-term alternative strategy. However, measuring pre- and existing levels of CTL cross-protection in humans is confounded by differences in infection histories across individuals. During 2000-2003, H1N2 viruses circulated persistently in the human population for the first time and we hypothesized that the viral nucleoprotein (NP) contained novel CTL epitopes that may have contributed to the survival of the viruses. This study describes the immunogenic NP peptides of H1N1, H2N2, and H3N2 influenza viruses isolated from humans over the past century, 1918-2003, by comparing this historical dataset to reference NP peptides from H1N2 that circulated in humans during 2000-2003. Observed peptides sequences ranged from highly conserved (15%) to highly variable (12%), with variation unrelated to reported immunodominance. No unique NP peptides which were exclusive to the H1N2 viruses were noted. However, the virus had inherited the NP from a recently emerged H3N2 variant containing novel peptides, which may have assisted its persistence. Any advantage due to this novelty was subsequently lost with emergence of a newer H3N2 variant in 2003. Our approach has potential to provide insight into the population context in which influenza viruses emerge, and may help to inform immunogenic peptide selection for CTL-inducing influenza vaccines. J. Med. Virol. 88:1725-1732, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  8. A human monoclonal antibody derived from a vaccinated volunteer recognizes heterosubtypically a novel epitope on the hemagglutinin globular head of H1 and H9 influenza A viruses

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Boonsathorn, Naphatsawan; Panthong, Sumolrat; Japan Science and Technology Agency/Japan International Cooperation Agency, Science and Technology Research Partnership for Sustainable Development

    Highlights: • A human monoclonal antibody against influenza virus was produced from a volunteer. • The antibody was generated from the PBMCs of the volunteer using the fusion method. • The antibody neutralized heterosubtypically group 1 influenza A viruses (H1 and H9). • The antibody targeted a novel epitope in globular head region of the hemagglutinin. • Sequences of the identified epitope are highly conserved among H1 and H9 subtypes. - Abstract: Most neutralizing antibodies elicited during influenza virus infection or by vaccination have a narrow spectrum because they usually target variable epitopes in the globular head region of hemagglutininmore » (HA). In this study, we describe a human monoclonal antibody (HuMAb), 5D7, that was prepared from the peripheral blood lymphocytes of a vaccinated volunteer using the fusion method. The HuMAb heterosubtypically neutralizes group 1 influenza A viruses, including seasonal H1N1, 2009 pandemic H1N1 (H1N1pdm) and avian H9N2, with a strong hemagglutinin inhibition activity. Selection of an escape mutant showed that the HuMAb targets a novel conformational epitope that is located in the HA head region but is distinct from the receptor binding site. Furthermore, Phe114Ile substitution in the epitope made the HA unrecognizable by the HuMAb. Amino acid residues in the predicted epitope region are also highly conserved in the HAs of H1N1 and H9N2. The HuMAb reported here may be a potential candidate for the development of therapeutic/prophylactic antibodies against H1 and H9 influenza viruses.« less

  9. Evaluation of protective efficacy of three novel H3N2 canine influenza vaccines

    PubMed Central

    Li, Lutao; Li, Xiuzhen; Hu, Renjun; Jia, Kun; Sun, Lingshuang; Yuan, Ziguo; Li, Shoujun

    2017-01-01

    Canine influenza virus (CIV) has the potential risk to spread in different areas and dog types. Thus, there is a growing need to develop an effective vaccine to control CIV disease. Here, we developed three vaccine candidates: 1) a recombinant pVAX1 vector expressing H3N2 CIV hemagglutinin (pVAX1-HA); 2) a live attenuated canine adenovirus type 2 expressing H3N2 CIV hemagglutinin (rCAV2-HA); and 3) an inactivated H3N2 CIV (A/canine/Guangdong/01/2006 (H3N2)). Mice received an initial intramuscular immunization that followed two booster injections at 2 and 4 weeks post-vaccination (wpv). The splenic lymphocytes were collected to assess the immune responses at 6 wpv. The protective efficacy was evaluated by challenging H3N2 CIV after vaccination (at 6 wpv). Our results demonstrated that all three vaccine candidates elicited cytokine and antibody responses in mice. The rCAV2-HA vaccine and the inactivated vaccine generated efficient protective efficacy in mice, whereas limited protection was provided by the pVAX1-HA DNA vaccine. Therefore, both the rCAV2-HA live recombinant virus and the inactivated CIV could be used as potential novel vaccines against H3N2CIV. This study provides guidance for choosing the most appropriate vaccine for the prevention and control of CIV disease. PMID:29228675

  10. From the Patient Perspective: the Economic Value of Seasonal and H1N1 Influenza Vaccination

    PubMed Central

    Lee, Bruce Y.; Bacon, Kristina; Donohue, Julie M.; Wiringa, Ann E.; Bailey, Rachel R.; Zimmerman, Richard K.

    2011-01-01

    Although studies have suggested that a patient’s perceived cost-benefit of a medical intervention could affect his or her utilization of the intervention, the economic value of influenza vaccine from the patient’s perspective remains unclear. Therefore, we developed a stochastic decision analytic computer model representing an adult’s decision of whether to get vaccinated. Different scenarios explored the impact of the patient being insured versus uninsured, influenza attack rate, vaccine administration costs and vaccination time costs. Results indicated that cost of avoiding influenza was fairly low, with one driver being required vaccination time. To encourage vaccination, decision makers may want to focus on ways to reduce this time, such as vaccinating at work, churches, or other normally frequented locations. PMID:21215340

  11. Human T-cells directed to seasonal influenza A virus cross-react with 2009 pandemic influenza A (H1N1) and swine-origin triple-reassortant H3N2 influenza viruses.

    PubMed

    Hillaire, Marine L B; Vogelzang-van Trierum, Stella E; Kreijtz, Joost H C M; de Mutsert, Gerrie; Fouchier, Ron A M; Osterhaus, Albert D M E; Rimmelzwaan, Guus F

    2013-03-01

    Virus-specific CD8(+) T-cells contribute to protective immunity against influenza A virus (IAV) infections. As the majority of these cells are directed to conserved viral proteins, they may afford protection against IAVs of various subtypes. The present study assessed the cross-reactivity of human CD8(+) T-lymphocytes, induced by infection with seasonal A (H1N1) or A (H3N2) influenza virus, with 2009 pandemic influenza A (H1N1) virus [A(H1N1)pdm09] and swine-origin triple-reassortant A (H3N2) [A(H3N2)v] viruses that are currently causing an increasing number of human cases in the USA. It was demonstrated that CD8(+) T-cells induced after seasonal IAV infections exerted lytic activity and produced gamma interferon upon in vitro restimulation with A(H1N1)pdm09 and A(H3N2)v influenza A viruses. Furthermore, CD8(+) T-cells directed to A(H1N1)pdm09 virus displayed a high degree of cross-reactivity with A(H3N2)v viruses. It was concluded that cross-reacting T-cells had the potential to afford protective immunity against A(H1N1)pdm09 viruses during the pandemic and offer some degree of protection against infection with A(H3N2)v viruses.

  12. Genetic characterization of circulating seasonal Influenza A viruses (2005-2009) revealed introduction of oseltamivir resistant H1N1 strains during 2009 in eastern India.

    PubMed

    Agrawal, Anurodh S; Sarkar, Mehuli; Ghosh, Swati; Roy, Tapasi; Chakrabarti, Sekhar; Lal, Renu; Mishra, Akhilesh C; Chadha, Mandeep S; Chawla-Sarkar, Mamta

    2010-12-01

    Influenza surveillance was implemented in Kolkata, eastern India in 2005 to identify the circulating subtypes and characterize their genetic diversity. Throat and nasal swabs were collected from outpatients with influenza-like illness (ILI). Of 2844 ILI cases identified at two referral hospitals during October 2005-September 2009, 309 (10.86%) were positive for Influenza A by real time RT-PCR, of which 110 (35.60%) were subtyped as H1N1 and 199 (64.40%) as H3N2. Comparison of the nucleotide (nt) and amino acid (aa) sequences of the HA1 gene for H1N1 and H3N2 strains showed that a subset of strains precede WHO recommended contemporary strains by 1-2 years. The Kolkata H1N1 strains clustered in Clade II, subgroup 2B with A/Brisbane/59/2007 but were distant from the corresponding vaccine strains (New Caledonia/20/99 and A/Solomon Island/3/06). The 2005-06 and 2007 H3N2 strains (15/17) clustered either A/Brisbane/10/2007-like (n=8) or A/Nepal/921/2006 like (n=7) strains, whereas 2008 strains (8/12) and 2009 strains (4/4) were similar to the 2010-11 vaccine strain A/Perth/16/2009. More aa substitutions were found in HA or NA genes of H3N2 than in H1N1 strains. No mutation conferring neuraminidase resistance was observed in any of the strain during 2005-08, however in 2009, drug resistant marker (H275Y) was present in seasonal H1N1, but not in co-circulating H3N2 strains. This is the first report of genetic characterization of circulating Influenza A strains from India. The results also highlight the importance of continuing Influenza surveillance in developing countries of Asia for monitoring unusual strains with pandemic potential and mutations conferring antiviral resistance. Copyright © 2010 Elsevier B.V. All rights reserved.

  13. Repeated seasonal influenza vaccination among elderly in Europe: Effects on laboratory confirmed hospitalised influenza.

    PubMed

    Rondy, Marc; Launay, Odile; Castilla, Jesus; Costanzo, Simona; Puig-Barberà, Joan; Gefenaite, Giedre; Larrauri, Amparo; Rizzo, Caterina; Pitigoi, Daniela; Syrjänen, Ritva K; Machado, Ausenda; Kurečić Filipović, Sanja; Krisztina Horváth, Judit; Paradowska-Stankiewicz, Iwona; Marbus, Sierk; Moren, Alain

    2017-08-03

    In Europe, annual influenza vaccination is recommended to elderly. From 2011 to 2014 and in 2015-16, we conducted a multicentre test negative case control study in hospitals of 11 European countries to measure influenza vaccine effectiveness (IVE) against laboratory confirmed hospitalised influenza among people aged ≥65years. We pooled four seasons data to measure IVE by past exposures to influenza vaccination. We swabbed patients admitted for clinical conditions related to influenza with onset of severe acute respiratory infection ≤7days before admission. Cases were patients RT-PCR positive for influenza virus and controls those negative for any influenza virus. We documented seasonal vaccination status for the current season and the two previous seasons. We recruited 5295 patients over the four seasons, including 465A(H1N1)pdm09, 642A(H3N2), 278 B case-patients and 3910 controls. Among patients unvaccinated in both previous two seasons, current seasonal IVE (pooled across seasons) was 30% (95%CI: -35 to 64), 8% (95%CI: -94 to 56) and 33% (95%CI: -43 to 68) against influenza A(H1N1)pdm09, A(H3N2) and B respectively. Among patients vaccinated in both previous seasons, current seasonal IVE (pooled across seasons) was -1% (95%CI: -80 to 43), 37% (95%CI: 7-57) and 43% (95%CI: 1-68) against influenza A(H1N1)pdm09, A(H3N2) and B respectively. Our results suggest that, regardless of patients' recent vaccination history, current seasonal vaccine conferred some protection to vaccinated patients against hospitalisation with influenza A(H3N2) and B. Vaccination of patients already vaccinated in both the past two seasons did not seem to be effective against A(H1N1)pdm09. To better understand the effect of repeated vaccination, engaging in large cohort studies documenting exposures to vaccine and natural infection is needed. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  14. Leptin and Leptin-Related Gene Polymorphisms, Obesity, and Influenza A/H1N1 Vaccine–Induced Immune Responses in Older Individuals

    PubMed Central

    Ovsyannikova, Inna G.; White, Sarah J.; Larrabee, Beth R.; Grill, Diane E.; Jacobson, Robert M.; Poland, Gregory A.

    2014-01-01

    Obesity is a risk factor for complicated influenza A/H1N1 disease and poor vaccine immunogenicity. Leptin, an adipocyte-derived hormone/cytokine, has many immune regulatory functions and therefore could explain susceptibility to infections and poor vaccine outcomes. We recruited 159 healthy adults (5074 years old) who were immunized with inactivated TIV influenza vacci–ne that contained A/California/7/2009/H1N1 virus. We found a strong correlation between leptin concentration and BMI (r=0.55, p<0.0001), but no association with hemagglutination antibody inhibition (HAI), B-cell, or granzyme B responses. We found a slight correlation between leptin concentration and an immunosenescence marker (TREC: T-cell receptor excision circles) level (r=0.23, p=0.01). We found eight SNPs in the LEP/LEPR/GHRL genes that were associated with leptin levels and four SNPs in the PTPN1/LEPR/STAT3 genes associated with peripheral blood TREC levels (p<0.05). Heterozygosity of the synonymous variant rs2230604 in the PTPN1 gene was associated with a significantly lower (531 vs. 259, p = 0.005) TREC level, as compared to the homozygous major variant. We also found eight SNPs in the LEP/PPARG/CRP genes associated with variations in influenza-specific HAI and B-cell responses (p<0.05). Our results suggest that specific allelic variations in the leptin-related genes may influence adaptive immune responses to influenza vaccine. PMID:24360890

  15. Novel triple-reassortant H1N1 swine influenza viruses in pigs in Tianjin, Northern China.

    PubMed

    Sun, Ying-Feng; Wang, Xiu-Hui; Li, Xiu-Li; Zhang, Li; Li, Hai-Hua; Lu, Chao; Yang, Chun-Lei; Feng, Jing; Han, Wei; Ren, Wei-Ke; Tian, Xiang-Xue; Tong, Guang-Zhi; Wen, Feng; Li, Ze-Jun; Gong, Xiao-Qian; Liu, Xiao-Min; Ruan, Bao-Yang; Yan, Ming-Hua; Yu, Hai

    2016-02-01

    Pigs are susceptible to both human and avian influenza viruses and therefore have been proposed to be mixing vessels for the generation of pandemic influenza viruses through reassortment. In this study, for the first time, we report the isolation and genetic analyses of three novel triple-reassortant H1N1 swine influenza viruses from pigs in Tianjin, Northern China. Phylogenetic analysis showed that these novel viruses contained genes from the 2009 pandemic H1N1 (PB2, PB1, PA and NP), Eurasian swine (HA, NA and M) and triple-reassortant swine (NS) lineages. This indicated that the reassortment among the 2009 pandemic H1N1, Eurasian swine and triple-reassortant swine influenza viruses had taken place in pigs in Tianjin and resulted in the generation of new viruses. Furthermore, three human-like H1N1, two classical swine H1N1 and two Eurasian swine H1N1 viruses were also isolated during the swine influenza virus surveillance from 2009 to 2013, which indicated that multiple genetic lineages of swine H1N1 viruses were co-circulating in the swine population in Tianjin, China. The emergence of novel triple-reassortant H1N1 swine influenza viruses may be a potential threat to human health and emphasizes the importance of further continuous surveillance. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. Technology transfer of oil-in-water emulsion adjuvant manufacturing for pandemic influenza vaccine production in Romania: Preclinical evaluation of split virion inactivated H5N1 vaccine with adjuvant.

    PubMed

    Stavaru, Crina; Onu, Adrian; Lupulescu, Emilia; Tucureanu, Catalin; Rasid, Orhan; Vlase, Ene; Coman, Cristin; Caras, Iuliana; Ghiorghisor, Alina; Berbecila, Laurentiu; Tofan, Vlad; Bowen, Richard A; Marlenee, Nicole; Hartwig, Airn; Bielefeldt-Ohmann, Helle; Baldwin, Susan L; Van Hoeven, Neal; Vedvick, Thomas S; Huynh, Chuong; O'Hara, Michael K; Noah, Diana L; Fox, Christopher B

    2016-04-02

    Millions of seasonal and pandemic influenza vaccine doses containing oil-in-water emulsion adjuvant have been administered in order to enhance and broaden immune responses and to facilitate antigen sparing. Despite the enactment of a Global Action Plan for Influenza Vaccines and a multi-fold increase in production capabilities over the past 10 years, worldwide capacity for pandemic influenza vaccine production is still limited. In developing countries, where routine influenza vaccination is not fully established, additional measures are needed to ensure adequate supply of pandemic influenza vaccines without dependence on the shipment of aid from other, potentially impacted first-world countries. Adaptation of influenza vaccine and adjuvant technologies by developing country influenza vaccine manufacturers may enable antigen sparing and corresponding increases in global influenza vaccine coverage capacity. Following on previously described work involving the technology transfer of oil-in-water emulsion adjuvant manufacturing to a Romanian vaccine manufacturing institute, we herein describe the preclinical evaluation of inactivated split virion H5N1 influenza vaccine with emulsion adjuvant, including immunogenicity, protection from virus challenge, antigen sparing capacity, and safety. In parallel with the evaluation of the bioactivity of the tech-transferred adjuvant, we also describe the impact of concurrent antigen manufacturing optimization activities. Depending on the vaccine antigen source and manufacturing process, inclusion of adjuvant was shown to enhance and broaden functional antibody titers in mouse and rabbit models, promote protection from homologous virus challenge in ferrets, and facilitate antigen sparing. Besides scientific findings, the operational lessons learned are delineated in order to facilitate adaptation of adjuvant technologies by other developing country institutes to enhance global pandemic influenza preparedness.

  17. Pandemic 2009 influenza A (H1N1) infection among 2009 Hajj Pilgrims from Southern Iran: a real-time RT-PCR-based study.

    PubMed

    Ziyaeyan, Mazyar; Alborzi, Abdolvahab; Jamalidoust, Marziyeh; Moeini, Mahsa; Pouladfar, Gholam R; Pourabbas, Bahman; Namayandeh, Mandana; Moghadami, Mohsen; Bagheri-Lankarani, Kamran; Mokhtari-Azad, Talat

    2012-11-01

    Hajj is a mass gathering undertaken annually in Mecca, Saudi Arabia. The 2009 Hajj coincided with both the pandemic influenza A/H1N1 2009 (A(H1N1)pdm09) and seasonal types of influenza A viruses. The interaction between pandemic influenza and Hajj could cause both a high level of mortality among the pilgrims and the spread of infection in their respective countries upon their return home. The present study attempted to determine the point prevalence of A(H1N1)pdm09 among returning Iranian pilgrims, most of whom had been vaccinated for seasonal influenza but not A(H1N1)pdm09. Pharyngeal swabs were collected from 305 pilgrims arriving at the airport in Shiraz, Iran. RNA was extracted from the samples and A(H1N1)pdm09 and other seasonal influenza A viruses were detected using TaqMan real-time PCR. For A(H1N1)pdm09-positive samples, the sensitivity to oseltamivir was also evaluated. Subjects included 132 (43.3%) men and 173 (56.7%) women, ranging in age from 24 to 65 years. The A(H1N1)pdm09 virus was detected in five (1.6%) pilgrims and other influenza A viruses in eight (2.6%). All the A(H1N1)pdm09 were sensitive to oseltamivir. Only five cases were found to be positive for A(H1N1)pdm09, and it seems unlikely that the arrival of infected pilgrims to their homelands would cause an outbreak of a new wave of infection there. Thus, the low morbidity and mortality rates among the pilgrims could be attributed to the characteristics of A(H1N1)pdm09, which causes morbidity and mortality in a way similar to the seasonal influenza infections, absence of high-risk individuals among the Iranian pilgrims, and the instructions given to them about contact and hand hygiene, and respiratory etiquette. © 2012 Blackwell Publishing Ltd.

  18. Role of vaccination-induced immunity and antigenic distance in the transmission dynamics of highly pathogenic avian influenza H5N1

    PubMed Central

    Rousou, Xanthoula; Kalthoff, Donata; Beer, Martin

    2016-01-01

    Highly pathogenic avian influenza (HPAI) H5N1 epidemics in poultry cause huge economic losses as well as sporadic human morbidity and mortality. Vaccination in poultry has often been reported as being ineffective in preventing transmission and as a potential driving force in the selection of immune escape mutants. We conducted transmission experiments to evaluate the transmission dynamics of HPAI H5N1 strains in chickens vaccinated with high and low doses of immune escape mutants we have previously selected, and analysed the data using mathematical models. Remarkably, we demonstrate that the effect of antigenic distances between the vaccine and challenge strains used in this study is too small to influence the transmission dynamics of the strains used. This is because the effect of a sufficient vaccine dose on antibody levels against the challenge viruses is large enough to compensate for any decrease in antibody titres due to antigenic differences between vaccine and challenge strains. Our results show that at least under experimental conditions, vaccination will remain effective even after antigenic changes as may be caused by the initial selection in vaccinated birds. PMID:26763336

  19. Combinatorial antibody libraries from survivors of the Turkish H5N1 avian influenza outbreak reveal virus neutralization strategies.

    PubMed

    Kashyap, Arun K; Steel, John; Oner, Ahmet F; Dillon, Michael A; Swale, Ryann E; Wall, Katherine M; Perry, Kimberly J; Faynboym, Aleksandr; Ilhan, Mahmut; Horowitz, Michael; Horowitz, Lawrence; Palese, Peter; Bhatt, Ramesh R; Lerner, Richard A

    2008-04-22

    The widespread incidence of H5N1 influenza viruses in bird populations poses risks to human health. Although the virus has not yet adapted for facile transmission between humans, it can cause severe disease and often death. Here we report the generation of combinatorial antibody libraries from the bone marrow of five survivors of the recent H5N1 avian influenza outbreak in Turkey. To date, these libraries have yielded >300 unique antibodies against H5N1 viral antigens. Among these antibodies, we have identified several broadly reactive neutralizing antibodies that could be used for passive immunization against H5N1 virus or as guides for vaccine design. The large number of antibodies obtained from these survivors provide a detailed immunochemical analysis of individual human solutions to virus neutralization in the setting of an actual virulent influenza outbreak. Remarkably, three of these antibodies neutralized both H1 and H5 subtype influenza viruses.

  20. 75 FR 10268 - Pandemic Influenza Vaccines-Amendment

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-05

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Office of the Secretary Pandemic Influenza Vaccines... Preparedness Act for H5N1, H2, H6, H7, H9 and 2009-H1N1 Vaccines: Whereas there are or may be multiple animal... through February 28, 2010 for vaccines against influenza virus strains named in the Declaration other than...

  1. Seroprevalence of H1N1, H3N2 and H1N2 influenza viruses in pigs in seven European countries in 2002-2003.

    PubMed

    Van Reeth, Kristien; Brown, Ian H; Dürrwald, Ralf; Foni, Emanuela; Labarque, Geoffrey; Lenihan, Patrick; Maldonado, Jaime; Markowska-Daniel, Iwona; Pensaert, Maurice; Pospisil, Zdenek; Koch, Guus

    2008-05-01

    Avian-like H1N1 and human-like H3N2 swine influenza viruses (SIV) have been considered widespread among pigs in Western Europe since the 1980s, and a novel H1N2 reassortant with a human-like H1 emerged in the mid 1990s. This study, which was part of the EC-funded 'European Surveillance Network for Influenza in Pigs 1', aimed to determine the seroprevalence of the H1N2 virus in different European regions and to compare the relative prevalences of each SIV between regions. Laboratories from Belgium, the Czech Republic, Germany, Italy, Ireland, Poland and Spain participated in an international serosurvey. A total of 4190 sow sera from 651 farms were collected in 2002-2003 and examined in haemagglutination inhibition tests against H1N1, H3N2 and H1N2. In Belgium, Germany, Italy and Spain seroprevalence rates to each of the three SIV subtypes were high (> or =30% of the sows seropositive) to very high (> or =50%), except for a lower H1N2 seroprevalence rate in Italy (13.8%). Most sows in these countries with high pig populations had antibodies to two or three subtypes. In Ireland, the Czech Republic and Poland, where swine farming is less intensive, H1N1 was the dominant subtype (8.0-11.7% seropositives) and H1N2 and H3N2 antibodies were rare (0-4.2% seropositives). Thus, SIV of H1N1, H3N2 and H1N2 subtype are enzootic in swine producing regions of Western Europe. In Central Europe, SIV activity is low and the circulation of H3N2 and H1N2 remains to be confirmed. The evolution and epidemiology of SIV throughout Europe is being further monitored through a second 'European Surveillance Network for Influenza in Pigs'.

  2. Novel reassortant influenza A(H1N2) virus derived from A(H1N1)pdm09 virus isolated from swine, Japan, 2012.

    PubMed

    Kobayashi, Miho; Takayama, Ikuyo; Kageyama, Tsutomu; Tsukagoshi, Hiroyuki; Saitoh, Mika; Ishioka, Taisei; Yokota, Yoko; Kimura, Hirokazu; Tashiro, Masato; Kozawa, Kunihisa

    2013-12-01

    We isolated a novel influenza virus A(H1N2) strain from a pig on January 13, 2012, in Gunma Prefecture, Japan. Phylogenetic analysis showed that the strain was a novel type of double-reassortant virus derived from the swine influenza virus strains H1N1pdm09 and H1N2, which were prevalent in Gunma at that time.

  3. Preparing for influenza after 2009 H1N1: special considerations for pregnant women and newborns.

    PubMed

    Rasmussen, Sonja A; Kissin, Dmitry M; Yeung, Lorraine F; MacFarlane, Kitty; Chu, Susan Y; Turcios-Ruiz, Reina M; Mitchell, Elizabeth W; Williams, Jennifer; Fry, Alicia M; Hageman, Jeffrey; Uyeki, Timothy M; Jamieson, Denise J

    2011-06-01

    Pregnant women and their newborn infants are at increased risk for influenza-associated complications, based on data from seasonal influenza and influenza pandemics. The Centers for Disease Control and Prevention (CDC) developed public health recommendations for these populations in response to the 2009 H1N1 pandemic. A review of these recommendations and information that was collected during the pandemic is needed to prepare for future influenza seasons and pandemics. The CDC convened a meeting entitled "Pandemic Influenza Revisited: Special Considerations for Pregnant Women and Newborns" on August 12-13, 2010, to gain input from experts and key partners on 4 main topics: antiviral prophylaxis and therapy, vaccine use, intrapartum/newborn (including infection control) issues, and nonpharmaceutical interventions and health care planning. Challenges to communicating recommendations regarding influenza to pregnant women and their health care providers were also discussed. After careful consideration of the available information and individual expert input, the CDC updated its recommendations for these populations for future influenza seasons and pandemics. Published by Mosby, Inc.

  4. Initial psychological responses to Influenza A, H1N1 ("Swine flu").

    PubMed

    Goodwin, Robin; Haque, Shamsul; Neto, Felix; Myers, Lynn B

    2009-10-06

    The outbreak of the pandemic flu, Influenza A H1N1 (Swine Flu) in early 2009, provided a major challenge to health services around the world. Previous pandemics have led to stockpiling of goods, the victimisation of particular population groups, and the cancellation of travel and the boycotting of particular foods (e.g. pork). We examined initial behavioural and attitudinal responses towards Influenza A, H1N1 ("Swine flu") in the six days following the WHO pandemic alert level 5, and regional differences in these responses. 328 respondents completed a cross-sectional Internet or paper-based questionnaire study in Malaysia (N = 180) or Europe (N = 148). Measures assessed changes in transport usage, purchase of preparatory goods for a pandemic, perceived risk groups, indicators of anxiety, assessed estimated mortality rates for seasonal flu, effectiveness of seasonal flu vaccination, and changes in pork consumption 26% of the respondents were 'very concerned' about being a flu victim (42% Malaysians, 5% Europeans, p < .001). 36% reported reduced public transport use (48% Malaysia, 22% Europe, p < .001), 39% flight cancellations (56% Malaysia, 17% Europe, p < .001). 8% had purchased preparatory materials (e.g. face masks: 8% Malaysia, 7% Europe), 41% Malaysia (15% Europe) intended to do so (p < .001). 63% of Europeans, 19% of Malaysians had discussed the pandemic with friends (p < .001). Groups seen as at 'high risk' of infection included the immune compromised (mentioned by 87% respondents), pig farmers (70%), elderly (57%), prostitutes/highly sexually active (53%), and the homeless (53%). In data collected only in Europe, 64% greatly underestimated the mortality rates of seasonal flu, 26% believed seasonal flu vaccination gave protection against swine flu. 7% had reduced/stopped eating pork. 3% had purchased anti-viral drugs for use at home, while 32% intended to do so if the pandemic worsened. Initial responses to Influenza A show large regional differences in

  5. Reassortant Avian Influenza A(H5N1) Viruses with H9N2-PB1 Gene in Poultry, Bangladesh

    PubMed Central

    Yamage, Mat; Dauphin, Gwenaëlle; Claes, Filip; Ahmed, Garba; Giasuddin, Mohammed; Salviato, Annalisa; Ormelli, Silvia; Bonfante, Francesco; Schivo, Alessia; Cattoli, Giovanni

    2013-01-01

    Bangladesh has reported a high number of outbreaks of highly pathogenic avian influenza (HPAI) (H5N1) in poultry. We identified a natural reassortant HPAI (H5N1) virus containing a H9N2-PB1 gene in poultry in Bangladesh. Our findings highlight the risks for prolonged co-circulation of avian influenza viruses and the need to monitor their evolution. PMID:24047513

  6. 2009 H1N1 influenza and experience in three critical care units.

    PubMed

    Teke, Turgut; Coskun, Ramazan; Sungur, Murat; Guven, Muhammed; Bekci, Taha T; Maden, Emin; Alp, Emine; Doganay, Mehmet; Erayman, Ibrahim; Uzun, Kursat

    2011-04-07

    We describe futures of ICU admission, demographic characteristics, treatment and outcome for critically ill patients with laboratory-confirmed and suspected infection with the H1N1 virus admitted to the three different critical care departments in Turkey. Retrospective study of critically ill patients with 2009 influenza A(H1N1) at ICU. Demographic data, symptoms, comorbid conditions, and clinical outcomes were collected using a case report form. Critical illness occurred in 61 patients admitted to an ICU with confirmed (n=45) or probable and suspected 2009 influenza A(H1N1). Patients were young (mean, 41.5 years), were female (54%). Fifty-six patients, required mechanical ventilation (14 invasive, 27 noninvasive, 15 both) during the course of ICU. On admission, mean APACHE II score was 18.7±6.3 and median PaO(2)/FIO(2) was 127.9±70.4. 31 patients (50.8%) was die. There were no significant differences in baseline PaO(2)/FIO(2 )and ventilation strategies between survivors and nonsurvivors. Patients who survived were more likely to have NIMV use at the time of admission to the ICU. Critical illness from 2009 influenza A(H1N1) in ICU predominantly affects young patients with little major comorbidity and had a high case-fatality rate. NIMV could be used in 2009 influenza A (H1N1) infection-related hypoxemic respiratory failure.

  7. An Influenza HA and M2e Based Vaccine Delivered by a Novel Attenuated Salmonella Mutant Protects Mice against Homologous H1N1 Infection.

    PubMed

    Hajam, Irshad A; Lee, John H

    2017-01-01

    Attenuated Salmonella strains constitute a promising technology for the development of a more efficient multivalent protein based vaccines. In this study, we constructed a novel attenuated strain of Salmonella for the delivery and expression of the H1N1 hemagglutinin (HA) and the conserved extracellular domain of the matrix protein 2 (M2e). We demonstrated that the constructed Salmonella strain exhibited efficient HA and M2e protein expressions and little cytotoxicity and pathogenicity in mice. Using BALB/c mice as the model, we showed that the mice vaccinated with a Salmonella strain expressing HA and M2e protein antigens, respectively, induced significant production of HA and M2e-specific serum IgG1 and IgG2a responses, and of anti-HA interferon-γ producing T cells. Furthermore, immunization with Salmonella-HA-M2e-based vaccine via different routes provided protection in 66.66% orally, 100% intramuscularly, and 100% intraperitoneally immunized mice against the homologous H1N1 virus while none of the animals survived treated with either the PBS or the Salmonella carrying empty expression vector. Ex vivo stimulated dendritic cells (DCs) with heat killed Salmonella expressing HA demonstrated that DCs play an important role in the elicitation of HA-specific humoral immune responses in mice. In summary, Salmonella -HA-M2e-based vaccine elicits efficient antigen-specific humoral and cellular immune responses, and provides significant immune protection against a highly pathogenic H1N1 influenza virus.

  8. Influenza A(H1N1)pdm09 outbreak detected in inter-seasonal months during the surveillance of influenza-like illness in Pune, India, 2012-2015.

    PubMed

    Gurav, Y K; Chadha, M S; Tandale, B V; Potdar, V A; Pawar, S D; Shil, P; Deoshatwar, A R; Aarthy, R; Bhushan, A

    2017-07-01

    An outbreak of influenza A(H1N1)pdm09 was detected during the ongoing community-based surveillance of influenza-like illness (ILI). Among reported 119 influenza A(H1N1)pdm09 cases (59 cases in the year 2012 and 60 cases in 2015) in summer months, common clinical features were fever (100%), cough (90·7%), sore throat (85·7%), nasal discharge (48·7%), headache (55·5%), fatigue (18·5%), breathlessness (3·4%), and ear discharge (1·7%). Rise in ILI cases were negatively correlated with the seasonal factors such as relative humidity (Karl Pearson's correlation coefficient, i.e. r = -0·71 in the year 2012 and r = -0·44 in the year 2015), while rise in ILI cases were positively correlated with the temperature difference (r = 0·44 in the year 2012 and r = 0·77 in the year 2015). The effective reproduction number R, was estimated to be 1·30 in 2012 and 1·64 in 2015. The study highlights the rise in unusual influenza activity in summer month with high attack rate of ILI among children aged ⩽9 years. Children in this age group may need special attention for influenza vaccination. Influenza A(H1N1)pdm09 outbreak was confirmed in inter-seasonal months during the surveillance of ILI in Pune, India, 2012-2015.

  9. The influence of the multi-basic cleavage site of the H5 hemagglutinin on the attenuation, immunogenicity and efficacy of a live attenuated influenza A h5N1 cold-adapted vaccine virus

    USDA-ARS?s Scientific Manuscript database

    A recombinant live attenuated influenza virus (LAIV) deltaH5N1 vaccine with a modified hemagglutinin (HA) and intact neuraminidase genes from A/Vietnam/1203/04 (H5N1) and the six remaining genome segments from A/Ann Arbor/6/60 (H2N2) cold-adapted (AA ca) virus was attenuated in chickens, mice and fe...

  10. Immunogenicity of influenza vaccine in colorectal cancer patients.

    PubMed

    Kim, Dong Ho; Lee, Yun Yong; Shin, Ui Sup; Moon, Sun Mi

    2013-12-01

    Although influenza is regarded as a major cause of morbidity and mortality in immunocompromised patients, vaccine coverage remains poor. We evaluated the immunogenicity of influenza vaccines in colorectal cancer patients. In this study, 40 colorectal cancer patients who received an influenza vaccine at the Korea Cancer Center Hospital during the 2009-2010 and 2010-2011 influenza seasons were analyzed. The blood samples were collected at prevaccination and 30 days post vaccination, and antibody titers were measured using the hemagglutination-inhibition tests. In the 2009-2011 season, the seroprotection rate for H1N1 (94.7%) was significantly higher than that for H3N2 (42.1%) and B (47.3%). The seroconversion rate was 52.6%, 26.3%, and 36.8% for H1N1, H3N2, and B, respectively. Fold increase of geometric mean titer (MFI) was 3.86, 1.49, and 3.33 for H1N1, H3N2, and B, respectively. In the 2010-2011 season, the seroprotection rate for H1N1 (57.1%) was significantly higher than that for H3N2 (52.4%) and B (38.1%). The seroconversion rate was 52.4%, 47.6% and 33.3% for H1N1, H3N2, and B, respectively. MFI was 12.29, 3.62 and 4.27 for H1N1, H3N2, and B, respectively. Our study cohort showed an acceptable immune response to an influenza vaccine without significant adverse effects, supporting the recommendation for annual influenza vaccination in colorectal cancer patients.

  11. Novel Reassortant Influenza A(H1N2) Virus Derived from A(H1N1)pdm09 Virus Isolated from Swine, Japan, 2012

    PubMed Central

    Kobayashi, Miho; Takayama, Ikuyo; Kageyama, Tsutomu; Tsukagoshi, Hiroyuki; Saitoh, Mika; Ishioka, Taisei; Yokota, Yoko; Kimura, Hirokazu; Tashiro, Masato

    2013-01-01

    We isolated a novel influenza virus A(H1N2) strain from a pig on January 13, 2012, in Gunma Prefecture, Japan. Phylogenetic analysis showed that the strain was a novel type of double-reassortant virus derived from the swine influenza virus strains H1N1pdm09 and H1N2, which were prevalent in Gunma at that time. PMID:24274745

  12. H1N1 seasonal influenza virus evolutionary rate changed over time.

    PubMed

    Suptawiwat, Ornpreya; Kongchanagul, Alita; Boonarkart, Chompunuch; Auewarakul, Prasert

    2018-05-02

    It was previously shown that the seasonal H1N1 influenza virus antigenic drift occurred at a slower rate than the seasonal H3N2 virus during the first decade of the 21th century. It was hypothesized that the slower antigenic evolution led to a decrease in average ages of infection, which in turn resulted in lower level of global viral circulation. It is unclear what caused the difference between the two viruses, but a plausible explanation may be related to the fact that the H1N1 virus had been in human population for much longer than the H3N2 virus. This would suggest that H1N1 antigenic drift in an earlier period may have been different from a more recent period. To test this hypothesis, we analyzed seasonal H1N1 influenza sequences during various time periods. In comparison to more recent H1N1 virus, the older H1N1 virus during the first half of the 20th century showed evidences of higher nonsynnonymous/synonymous ration (dN/dS) in its hemagglutinin (HA) gene. We compared amino acid sequence changes in the HA epitopes for each outbreak season and found that there were less changes in later years. Amino acid sequence diversity in the epitopes as measured by sequence entropy became smaller for each passing decade. These suggest that there might be some limit to the antigenic drift. The longer an influenza virus has drifted in human population, the less flexibility it may become. With less flexibility to adapt and escape the host immunity, the virus may have to rely more on younger naïve population. Copyright © 2018 Elsevier B.V. All rights reserved.

  13. Adaptation of Pandemic H1N1 Influenza Viruses in Mice▿

    PubMed Central

    Ilyushina, Natalia A.; Khalenkov, Alexey M.; Seiler, Jon P.; Forrest, Heather L.; Bovin, Nicolai V.; Marjuki, Henju; Barman, Subrata; Webster, Robert G.; Webby, Richard J.

    2010-01-01

    The molecular mechanism by which pandemic 2009 influenza A viruses were able to sufficiently adapt to humans is largely unknown. Subsequent human infections with novel H1N1 influenza viruses prompted an investigation of the molecular determinants of the host range and pathogenicity of pandemic influenza viruses in mammals. To address this problem, we assessed the genetic basis for increased virulence of A/CA/04/09 (H1N1) and A/TN/1-560/09 (H1N1) isolates, which are not lethal for mice, in a new mammalian host by promoting their mouse adaptation. The resulting mouse lung-adapted variants showed significantly enhanced growth characteristics in eggs, extended extrapulmonary tissue tropism, and pathogenicity in mice. All mouse-adapted viruses except A/TN/1-560/09-MA2 grew faster and to higher titers in cells than the original strains. We found that 10 amino acid changes in the ribonucleoprotein (RNP) complex (PB2 E158G/A, PA L295P, NP D101G, and NP H289Y) and hemagglutinin (HA) glycoprotein (K119N, G155E, S183P, R221K, and D222G) controlled enhanced mouse virulence of pandemic isolates. HA mutations acquired during adaptation affected viral receptor specificity by enhancing binding to α2,3 together with decreasing binding to α2,6 sialyl receptors. PB2 E158G/A and PA L295P amino acid substitutions were responsible for the significant enhancement of transcription and replication activity of the mouse-adapted H1N1 variants. Taken together, our findings suggest that changes optimizing receptor specificity and interaction of viral polymerase components with host cellular factors are the major mechanisms that contribute to the optimal competitive advantage of pandemic influenza viruses in mice. These modulators of virulence, therefore, may have been the driving components of early evolution, which paved the way for novel 2009 viruses in mammals. PMID:20592084

  14. H5N1-SeroDetect EIA and rapid test: a novel differential diagnostic assay for serodiagnosis of H5N1 infections and surveillance.

    PubMed

    Khurana, Surender; Sasono, Pretty; Fox, Annette; Nguyen, Van Kinh; Le, Quynh Mai; Pham, Quang Thai; Nguyen, Tran Hien; Nguyen, Thanh Liem; Horby, Peter; Golding, Hana

    2011-12-01

    Continuing evolution of highly pathogenic (HP) H5N1 influenza viruses in wild birds with transmission to domestic poultry and humans poses a pandemic threat. There is an urgent need for a simple and rapid serological diagnostic assay which can differentiate between antibodies to seasonal and H5N1 strains and that could provide surveillance tools not dependent on virus isolation and nucleic acid technologies. Here we describe the establishment of H5N1 SeroDetect enzyme-linked immunosorbent assay (ELISA) and rapid test assays based on three peptides in HA2 (488-516), PB1-F2 (2-75), and M2e (2-24) that are highly conserved within H5N1 strains. These peptides were identified by antibody repertoire analyses of H5N1 influenza survivors in Vietnam using whole-genome-fragment phage display libraries (GFPDLs). To date, both platforms have demonstrated high levels of sensitivity and specificity in detecting H5N1 infections (clade 1 and clade 2.3.4) in Vietnamese patients as early as 7 days and up to several years postinfection. H5N1 virus-uninfected individuals in Vietnam and the United States, including subjects vaccinated with seasonal influenza vaccines or with confirmed seasonal virus infections, did not react in the H5N1-SeroDetect assays. Moreover, sera from individuals vaccinated with H5N1 subunit vaccine with moderate anti-H5N1 neutralizing antibody titers did not react positively in the H5N1-SeroDetect ELISA or rapid test assays. The simple H5N1-SeroDetect ELISA and rapid tests could provide an important tool for large-scale surveillance for potential exposure to HP H5N1 strains in both humans and birds.

  15. [Investigation on a seasonal influenza accompanying with the first locale novel A/H1N1 influenza outbreak in China].

    PubMed

    Yuan, Jun; Li, Mei-xia; Liu, Yu-fei; Di, Biao; Xiao, Xiao-ling; Mao, Xin-wu; Wu, Ye-jian; Xie, Hua-ping; Xie, Zhao-jun; Zhang, Hao; Liu, Jian-ping; Li, Hai-lin; Shen, Ji-chuan; Yang, Zhi-cong; Wang, Ming

    2009-10-01

    To timely summarize past experience and to provide more pertinent reference for control and prevention in A/H1N1 cases in influenza season. During May 25 to 31, 2009, 2 secondary community cases caused by a influenza A/H1N1 imported case. In the close contacts of 3 A/H1N1 cases, 14 had some aspirator symptoms onset, such as fever (> or = 37.5 degrees C), cough, sore throat and etc. Laboratory tests excluded the infection of A/H1N1 influenza. For throat swab test for the 14 cases, 7 were tested for seasonal influenza virus. A face-to-face or telephone interview was conducted by CDC staff to collect information of 62 close contacts. Of 14 fever cases, there was no significant by differences by age[15-age group: 19.2% (5/26), over 25-age group: 25.0% (9/36); chi(2) = 0.287, P = 0.592]; by sex group [24.0% (6/25) for male and 21.6% (8/37) for female; chi(2) = 0.048, P = 0.826], by working units [dressing and design, photograph, saleroom and others, consumer group: 42.1% (8/19), 27.3% (3/11), 12.5% (2/16) and 6.3% (1/16); chi(2) = 7.653, P = 0.054], by dormitory style [dormitory style = 33.3% (4/12), non-dormitory style = 29.4% (10/34); chi(2) = 0.699, P = 0.403]. All the cases had fever (37.5 - 37.9 degrees C), no case had diarrhea. One in 3 A/H1N1 cases had diarrhea. All the 14 cases were negative result for A/H1N1 RNA. Six from 7 cases were positive for seasonal influenza test. This was a seasonal influenza outbreak happened in the close contacts of first confirmed A/H1N1 cases in community in mainland China. It showed that we should exclude the seasonal influenza in the investigation of A/H1N1 cases in the seasonal influenza period in some time. It is necessary to take effective measure to strengthen the control and prevention of seasonal influenza.

  16. Novel reassortant influenza viruses between pandemic (H1N1) 2009 and other influenza viruses pose a risk to public health.

    PubMed

    Kong, Weili; Wang, Feibing; Dong, Bin; Ou, Changbo; Meng, Demei; Liu, Jinhua; Fan, Zhen-Chuan

    2015-12-01

    Influenza A virus (IAV) is characterized by eight single-stranded, negative sense RNA segments, which allows for gene reassortment among different IAV subtypes when they co-infect a single host cell simultaneously. Genetic reassortment is an important way to favor the evolution of influenza virus. Novel reassortant virus may pose a pandemic among humans. In history, three human pandemic influenza viruses were caused by genetic reassortment between avian, human and swine influenza viruses. Since 2009, pandemic (H1N1) 2009 (pdm/09 H1N1) influenza virus composed of two swine influenza virus genes highlighted the genetic reassortment again. Due to wide host species and high transmission of the pdm/09 H1N1 influenza virus, many different avian, human or swine influenza virus subtypes may reassert with it to generate novel reassortant viruses, which may result in a next pandemic among humans. So, it is necessary to understand the potential threat of current reassortant viruses between the pdm/09 H1N1 and other influenza viruses to public health. This study summarized the status of the reassortant viruses between the pdm/09 H1N1 and other influenza viruses of different species origins in natural and experimental conditions. The aim of this summarization is to facilitate us to further understand the potential threats of novel reassortant influenza viruses to public health and to make effective prevention and control strategies for these pathogens. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. The influence of social-cognitive factors on personal hygiene practices to protect against influenzas: using modelling to compare avian A/H5N1 and 2009 pandemic A/H1N1 influenzas in Hong Kong.

    PubMed

    Liao, Qiuyan; Cowling, Benjamin J; Lam, Wendy Wing Tak; Fielding, Richard

    2011-06-01

    Understanding population responses to influenza helps optimize public health interventions. Relevant theoretical frameworks remain nascent. To model associations between trust in information, perceived hygiene effectiveness, knowledge about the causes of influenza, perceived susceptibility and worry, and personal hygiene practices (PHPs) associated with influenza. Cross-sectional household telephone surveys on avian influenza A/H5N1 (2006) and pandemic influenza A/H1N1 (2009) gathered comparable data on trust in formal and informal sources of influenza information, influenza-related knowledge, perceived hygiene effectiveness, worry, perceived susceptibility, and PHPs. Exploratory factor analysis confirmed domain content while confirmatory factor analysis was used to evaluate the extracted factors. The hypothesized model, compiled from different theoretical frameworks, was optimized with structural equation modelling using the A/H5N1 data. The optimized model was then tested against the A/H1N1 dataset. The model was robust across datasets though corresponding path weights differed. Trust in formal information was positively associated with perceived hygiene effectiveness which was positively associated with PHPs in both datasets. Trust in formal information was positively associated with influenza worry in A/H5N1 data, and with knowledge of influenza cause in A/H1N1 data, both variables being positively associated with PHPs. Trust in informal information was positively associated with influenza worry in both datasets. Independent of information trust, perceived influenza susceptibility associated with influenza worry. Worry associated with PHPs in A/H5N1 data only. Knowledge of influenza cause and perceived PHP effectiveness were associated with PHPs. Improving trust in formal information should increase PHPs. Worry was significantly associated with PHPs in A/H5N1.

  18. Pandemic 2009 influenza A (H1N1) infection among 2009 Hajj Pilgrims from Southern Iran: a real‐time RT‐PCR‐based study

    PubMed Central

    Ziyaeyan, Mazyar; Alborzi, Abdolvahab; Jamalidoust, Marziyeh; Moeini, Mahsa; Pouladfar, Gholam R.; Pourabbas, Bahman; Namayandeh, Mandana; Moghadami, Mohsen; Bagheri‐Lankarani, Kamran; Mokhtari‐Azad, Talat

    2012-01-01

    Please cite this paper as: Ziyaeyan et al. (2012) Pandemic 2009 influenza A H1N1 infection among 2009 Hajj Pilgrims from Southern Iran: a real‐time RT‐PCR‐based study. Influenza and Other Respiratory Viruses 6(601), e80–e84. Background  Hajj is a mass gathering undertaken annually in Mecca, Saudi Arabia. The 2009 Hajj coincided with both the pandemic influenza A/H1N1 2009 (A(H1N1)pdm09) and seasonal types of influenza A viruses. The interaction between pandemic influenza and Hajj could cause both a high level of mortality among the pilgrims and the spread of infection in their respective countries upon their return home. Objective  The present study attempted to determine the point prevalence of A(H1N1)pdm09 among returning Iranian pilgrims, most of whom had been vaccinated for seasonal influenza but not A(H1N1)pdm09. Methods  Pharyngeal swabs were collected from 305 pilgrims arriving at the airport in Shiraz, Iran. RNA was extracted from the samples and A(H1N1)pdm09 and other seasonal influenza A viruses were detected using TaqMan real‐time PCR. For A(H1N1)pdm09‐positive samples, the sensitivity to oseltamivir was also evaluated. Results  Subjects included 132 (43·3%) men and 173 (56·7%) women, ranging in age from 24 to 65 years. The A(H1N1)pdm09 virus was detected in five (1·6%) pilgrims and other influenza A viruses in eight (2·6%). All the A(H1N1)pdm09 were sensitive to oseltamivir. Conclusions  Only five cases were found to be positive for A(H1N1)pdm09, and it seems unlikely that the arrival of infected pilgrims to their homelands would cause an outbreak of a new wave of infection there. Thus, the low morbidity and mortality rates among the pilgrims could be attributed to the characteristics of A(H1N1)pdm09, which causes morbidity and mortality in a way similar to the seasonal influenza infections, absence of high‐risk individuals among the Iranian pilgrims, and the instructions given to them about contact and hand hygiene, and

  19. Novel (pandemic) influenza A H1N1 in healthcare facilities: implications for prevention and control.

    PubMed

    Maltezou, Helena C

    2010-07-01

    In April 2009 a novel (pandemic) influenza A H1N1 virus was identified in Mexico and the USA and spread throughout the world over a short period of time. Although the virulence of novel influenza was no greater than that of seasonal influenza, a major patient load and wave of admissions were faced. There are few evidence-based data available to guide infection control measures for novel influenza, however what is clear is that the novel virus is a very efficient agent for rapid spread and onset of outbreaks in healthcare settings. There are few reports on the nosocomial transmission of novel influenza, however outbreaks with severe morbidity and mortality may occur among high-risk groups. Last y efforts were made in several countries to build infection control capacity in healthcare facilities and to improve employee and patient safety. Adherence of healthcare workers to recommendations for vaccination against novel influenza and the use of personal protective equipment are emerging as major obstacles in achieving this goal. The use of N95 respirators instead of surgical masks for all close contacts, as recommended by the Centers for Disease Control and Prevention and in contrast with recommendations for seasonal influenza, is a major shift in everyday practice.

  20. Reassortant Eurasian Avian-Like Influenza A(H1N1) Virus from a Severely Ill Child, Hunan Province, China, 2015.

    PubMed

    Zhu, Wenfei; Zhang, Hong; Xiang, Xingyu; Zhong, Lili; Yang, Lei; Guo, Junfeng; Xie, Yiran; Li, Fangcai; Deng, Zhihong; Feng, Hong; Huang, Yiwei; Hu, Shixiong; Xu, Xin; Zou, Xiaohui; Li, Xiaodan; Bai, Tian; Chen, Yongkun; Li, Zi; Li, Junhua; Shu, Yuelong

    2016-11-01

    In 2015, a novel influenza A(H1N1) virus was isolated from a boy in China who had severe pneumonia. The virus was a genetic reassortant of Eurasian avian-like influenza A(H1N1) (EA-H1N1) virus. The hemagglutinin, neuraminidase, and matrix genes of the reassortant virus were highly similar to genes in EA-H1N1 swine influenza viruses, the polybasic 1 and 2, polymerase acidic, and nucleoprotein genes originated from influenza A(H1N1)pdm09 virus, and the nonstructural protein gene derived from classical swine influenza A(H1N1) (CS H1N1) virus. In a mouse model, the reassortant virus, termed influenza A/Hunan/42443/2015(H1N1) virus, showed higher infectivity and virulence than another human EA-H1N1 isolate, influenza A/Jiangsu/1/2011(H1N1) virus. In the respiratory tract of mice, virus replication by influenza A/Hunan/42443/2015(H1N1) virus was substantially higher than that by influenza A/Jiangsu/1/2011(H1N1) virus. Human-to-human transmission of influenza A/Hunan/42443/2015(H1N1) virus has not been detected; however, given the circulation of novel EA-H1N1 viruses in pigs, enhanced surveillance should be instituted among swine and humans.

  1. Reassortant Eurasian Avian-Like Influenza A(H1N1) Virus from a Severely Ill Child, Hunan Province, China, 2015

    PubMed Central

    Zhu, Wenfei; Zhang, Hong; Xiang, Xingyu; Zhong, Lili; Yang, Lei; Guo, Junfeng; Xie, Yiran; Li, Fangcai; Deng, Zhihong; Feng, Hong; Huang, Yiwei; Hu, Shixiong; Xu, Xin; Zou, Xiaohui; Li, Xiaodan; Bai, Tian; Chen, Yongkun; Li, Zi

    2016-01-01

    In 2015, a novel influenza A(H1N1) virus was isolated from a boy in China who had severe pneumonia. The virus was a genetic reassortant of Eurasian avian-like influenza A(H1N1) (EA-H1N1) virus. The hemagglutinin, neuraminidase, and matrix genes of the reassortant virus were highly similar to genes in EA-H1N1 swine influenza viruses, the polybasic 1 and 2, polymerase acidic, and nucleoprotein genes originated from influenza A(H1N1)pdm09 virus, and the nonstructural protein gene derived from classical swine influenza A(H1N1) (CS H1N1) virus. In a mouse model, the reassortant virus, termed influenza A/Hunan/42443/2015(H1N1) virus, showed higher infectivity and virulence than another human EA-H1N1 isolate, influenza A/Jiangsu/1/2011(H1N1) virus. In the respiratory tract of mice, virus replication by influenza A/Hunan/42443/2015(H1N1) virus was substantially higher than that by influenza A/Jiangsu/1/2011(H1N1) virus. Human-to-human transmission of influenza A/Hunan/42443/2015(H1N1) virus has not been detected; however, given the circulation of novel EA-H1N1 viruses in pigs, enhanced surveillance should be instituted among swine and humans. PMID:27767007

  2. Molecular characterization of a novel reassortant H1N2 influenza virus containing genes from the 2009 pandemic human H1N1 virus in swine from eastern China.

    PubMed

    Peng, Xiuming; Wu, Haibo; Xu, Lihua; Peng, Xiaorong; Cheng, Linfang; Jin, Changzhong; Xie, Tiansheng; Lu, Xiangyun; Wu, Nanping

    2016-06-01

    Pandemic outbreaks of H1N1 swine influenza virus have been reported since 2009. Reassortant H1N2 viruses that contain genes from the pandemic H1N1 virus have been isolated in Italy and the United States. However, there is limited information regarding the molecular characteristics of reassortant H1N2 swine influenza viruses in eastern China. Active influenza surveillance programs in Zhejiang Province identified a novel H1N2 influenza virus isolated from pigs displaying clinical signs of influenza virus infection. Whole-genome sequencing was performed and this strain was compared with other influenza viruses available in GenBank. Phylogenetic analysis suggested that the novel strain contained genes from the 2009 pandemic human H1N1 and swine H3N2 viruses. BALB/c mice were infected with the isolated virus to assess its virulence in mice. While the novel H1N2 isolate replicated well in mice, it was found to be less virulent. These results provide additional evidence that swine serve as intermediate hosts or 'mixing vessels' for novel influenza viruses. They also emphasize the importance of surveillance in the swine population for use as an early warning system for influenza outbreaks in swine and human populations.

  3. The hemagglutinin structure of an avian H1N1 influenza A virus

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lin, Tianwei; Wang, Gengyan; Li, Anzhang

    2009-09-15

    The interaction between hemagglutinin (HA) and receptors is a kernel in the study of evolution and host adaptation of H1N1 influenza A viruses. The notion that the avian HA is associated with preferential specificity for receptors with Sia{alpha}2,3Gal glycosidic linkage over those with Sia{alpha}2,6Gal linkage is not all consistent with the available data on H1N1 viruses. By x-ray crystallography, the HA structure of an avian H1N1 influenza A virus, as well as its complexes with the receptor analogs, was determined. The structures revealed no preferential binding of avian receptor analogs over that of the human analog, suggesting that the HA/receptormore » binding might not be as stringent as is commonly believed in determining the host receptor preference for some subtypes of influenza viruses, such as the H1N1 viruses. The structure also showed difference in glycosylation despite the preservation of related sequences, which may partly contribute to the difference between structures of human and avian origin.« less

  4. Neurological and autoimmune disorders after vaccination against pandemic influenza A (H1N1) with a monovalent adjuvanted vaccine: population based cohort study in Stockholm, Sweden

    PubMed Central

    Persson, Ingemar; Örtqvist, Åke; Bergman, Ulf; Ludvigsson, Jonas F; Granath, Fredrik

    2011-01-01

    Objective To examine the risk of neurological and autoimmune disorders of special interest in people vaccinated against pandemic influenza A (H1N1) with Pandemrix (GlaxoSmithKline, Middlesex, UK) compared with unvaccinated people over 8-10 months. Design Retrospective cohort study linking individualised data on pandemic vaccinations to an inpatient and specialist database on healthcare utilisation in Stockholm county for follow-up during and after the pandemic period. Setting Stockholm county, Sweden. Population All people registered in Stockholm county on 1 October 2009 and who had lived in this region since 1 January 1998; 1 024 019 were vaccinated against H1N1 and 921 005 remained unvaccinated. Main outcome measures Neurological and autoimmune diagnoses according to the European Medicines Agency strategy for monitoring of adverse events of special interest defined using ICD-10 codes for Guillain-Barré syndrome, Bell’s palsy, multiple sclerosis, polyneuropathy, anaesthesia or hypoaesthesia, paraesthesia, narcolepsy (added), and autoimmune conditions such as rheumatoid arthritis, inflammatory bowel disease, and type 1 diabetes; and short term mortality according to vaccination status. Results Excess risks among vaccinated compared with unvaccinated people were of low magnitude for Bell’s palsy (hazard ratio 1.25, 95% confidence interval 1.06 to 1.48) and paraesthesia (1.11, 1.00 to 1.23) after adjustment for age, sex, socioeconomic status, and healthcare utilisation. Risks for Guillain-Barré syndrome, multiple sclerosis, type 1 diabetes, and rheumatoid arthritis remained unchanged. The risks of paraesthesia and inflammatory bowel disease among those vaccinated in the early phase (within 45 days from 1 October 2009) of the vaccination campaign were significantly increased; the risk being increased within the first six weeks after vaccination. Those vaccinated in the early phase were at a slightly reduced risk of death than those who were unvaccinated (0

  5. Exploring the effect of previous inactivated influenza vaccination on seasonal influenza vaccine effectiveness against medically attended influenza: Results of the European I-MOVE multicentre test-negative case-control study, 2011/2012-2016/2017.

    PubMed

    Valenciano, Marta; Kissling, Esther; Larrauri, Amparo; Nunes, Baltazar; Pitigoi, Daniela; O'Donnell, Joan; Reuss, Annicka; Horváth, Judit Krisztina; Paradowska-Stankiewicz, Iwona; Rizzo, Caterina; Falchi, Alessandra; Daviaud, Isabelle; Brytting, Mia; Meijer, Adam; Kaic, Bernard; Gherasim, Alin; Machado, Ausenda; Ivanciuc, Alina; Domegan, Lisa; Schweiger, Brunhilde; Ferenczi, Annamária; Korczyńska, Monika; Bella, Antonino; Vilcu, Ana-Maria; Mosnier, Anne; Zakikhany, Katherina; de Lange, Marit; Kurečić Filipovićović, Sanja; Johansen, Kari; Moren, Alain

    2018-04-16

    Results of previous influenza vaccination effects on current season influenza vaccine effectiveness (VE) are inconsistent. To explore previous influenza vaccination effects on current season VE among population targeted for vaccination. We used 2011/2012 to 2016/2017 I-MOVE primary care multicentre test-negative data. For each season, we compared current season adjusted VE (aVE) between individuals vaccinated and unvaccinated in previous season. Using unvaccinated in both seasons as a reference, we then compared aVE between vaccinated in both seasons, current only, and previous only. We included 941, 2645 and 959 influenza-like illness patients positive for influenza A(H1N1)pdm09, A(H3N2) and B, respectively, and 5532 controls. In 2011/2012, 2014/2015 and 2016/2017, A(H3N2) aVE point estimates among those vaccinated in previous season were -68%, -21% and -19%, respectively; among unvaccinated in previous season, these were 33%, 48% and 46%, respectively (aVE not computable for influenza A(H1N1)pdm09 and B). Compared to current season vaccination only, VE for both seasons' vaccination was (i) similar in two of four seasons for A(H3N2) (absolute difference [ad] 6% and 8%); (ii) lower in three of four seasons for influenza A(H1N1)pdm09 (ad 18%, 26% and 29%), in two seasons for influenza A(H3N2) (ad 27% and 39%) and in two of three seasons for influenza B (ad 26% and 37%); (iii) higher in one season for influenza A(H1N1)pdm09 (ad 20%) and influenza B (ad 24%). We did not identify any pattern of previous influenza vaccination effect. Prospective cohort studies documenting influenza infections, vaccinations and vaccine types are needed to understand previous influenza vaccinations' effects. © 2018 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.

  6. Supply of neuraminidase inhibitors related to reduced influenza A (H1N1) mortality during the 2009-2010 H1N1 pandemic: an ecological study.

    PubMed

    Miller, Paula E; Rambachan, Aksharananda; Hubbard, Roderick J; Li, Jiabai; Meyer, Alison E; Stephens, Peter; Mounts, Anthony W; Rolfes, Melissa A; Penn, Charles R

    2012-01-01

    The influenza A (H1N1) pandemic swept across the globe from April 2009 to August 2010 affecting millions. Many WHO Member States relied on antiviral drugs, specifically neuraminidase inhibitors (NAIs) oseltamivir and zanamivir, to treat influenza patients in critical condition. Such drugs have been found to be effective in reducing severity and duration of influenza illness, and likely reduced morbidity during the pandemic. However, it is less clear whether NAIs used during the pandemic reduced H1N1 mortality. Country-level data on supply of oseltamivir and zanamivir were used to predict H1N1 mortality (per 100,000 people) from July 2009 to August 2010 in forty-two WHO Member States. Poisson regression was used to model the association between NAI supply and H1N1 mortality, with adjustment for economic, demographic, and health-related confounders. After adjustment for potential confounders, each 10% increase in kilograms of oseltamivir, per 100,000 people, was associated with a 1.6% reduction in H1N1 mortality over the pandemic period (relative rate (RR) = 0.84 per log increase in oseltamivir supply). While the supply of zanamivir was considerably less than that of oseltamivir in each Member State, each 10% increase in kilogram of active zanamivir, per 100,000, was associated with a 0.3% reduction in H1N1 mortality (RR = 0.97 per log increase). While there are limitations to the ecologic nature of these data, this analysis offers evidence of a protective relationship between antiviral drug supply and influenza mortality and supports a role for influenza antiviral use in future pandemics.

  7. Influenza A (H1N1) in Rome, Italy in family: three case reports.

    PubMed

    Lisena, Francesco; Bordi, Licia; Carletti, Fabrizio; Castilletti, Concetta; Ferraro, Federica; Lalle, Eleonora; Lanini, Simone; Ruscitti, Luca Enrico; Fusco, Francesco Maria

    2009-12-01

    A new Influenza A virus H1N1 appeared in March-April 2009, and thousands of cases are being reported worldwide. In the initial months, several imported cases were reported in many European countries, while some countries reported local chains of transmission. We describe the first cluster of in-country transmission of the new Influenza A H1N1 which occurred in Italy, involving 3 patients. Patient 1, a 11-year-old male child developed fever, cough, and general malaise 4 days after returning from a travel to Mexico. Some days later, the 69-year-old grandfather (patient 2), who did not travel to Mexico, and the 33-month-old brother (patient 3) of patient 1 developed mild influenza symptoms. PCR tests resulted positive for Influenza A, and sequence analysis confirmed infection with the Influenza A (H1N1) strain for all three patients. Some problems were experienced in the administration of chemoprophylaxis and therapy in the patient 3. The chemoprophylaxis policies in other family members are described, too. Some interesting facts emerge from the analysis of this cluster. The transmission of Influenza A H1N1 virus seems to be dependent on strict contacts. Patient 2 and patient 3 did not take the chemoprophylaxis properly. The problems in the administration of chemoprophylaxis and therapy to patient 3 suggest that in infants specific individual-based strategies for assuring the correct administration are advisable.

  8. Evaluation of T and B memory cell responses elicited by the pandemic H1N1 vaccine in HIV-infected and HIV-uninfected individuals.

    PubMed

    Sun, Peifang; Crum-Cianflone, Nancy F; Defang, Gabriel; Williams, Maya; Ganesan, Anuradha; Agan, Brian K; Lalani, Tahaniyat; Whitman, Timothy; Brandt, Carolyn; Burgess, Timothy H

    2017-10-27

    This study was to compare B and T memory cells elicited by a single dose monovalent 2009 influenza A (H1N1) vaccine (strain A/California/7/2009 H1N1) in HIV + and HIV - groups, and to analyze the impact of the prior seasonal vaccines to the immunogenicity of this vaccine. Blood samples were collected before vaccination (day 0) and at days 28 and 180. Participants were categorized into HIV - /LAIV, HIV - /TIV and HIV + /TIV subgroups according to the trivalent live-attenuated or inactivated (LAIV or TIV) seasonal influenza vaccines they received previously. The IgG + memory B cells (B Mem ) and IFNγ + T cells were measured against antigens including the H1N1 vaccine, the hemagglutinin (HA) and neuraminidase (NA) proteins or peptide pools of the pandemic and the seasonal H1N1 strains, respectively. Overall B Mem responses increased significantly at day 28 but returned to baseline by day 180 in all three subgroups. The average frequency of the H1N1-specific B Mem at day 28 for the HIV - /LAIV, HIV - /TIV and HIV + /TIV groups was 2.14%, 1.26% and 1.67%, respectively, and the average fold change was 14.39, 3.81 and 3.93, respectively. The differences of B Mem between HIV - /LAIV and the two TIV subgroups were significant. For the IFNγ response, the overall spot counts ranged widely between 0 and 958/10 6 PBMCs. The group average spot counts to H1N1 vaccine was 89, 102, and 30 at day 28 for HIV - /LAIV, HIV - /TIV and HIV + /TIV subgroups, respectively. The average increase of IFNγ response at day 28 vs day 0 in all three subgroups did not reach 2-fold. Participants with a prior LAIV seasonal vaccine, as compared to a TIV seasonal vaccine, responded significantly better to the monovalent H1N1 vaccine. Excluding LAIV participants, no difference was seen between the HIV + and HIV - subject groups in terms of B Mem . The B Mem response declined at 6months. Copyright © 2017. Published by Elsevier Ltd.

  9. Phylogenetic relationships of the HA and NA genes between vaccine and seasonal influenza A(H3N2) strains in Korea

    PubMed Central

    Park, Sehee; Bae, Joon-Yong; Yoo, Kirim; Cheong, Hee Jin; Noh, Ji Yun; Hong, Kyung Wook; Lemey, Philippe; Vrancken, Bram; Kim, Juwon; Nam, Misun; Yun, Soo-Hyeon; Cho, Woo In; Song, Joon Young; Kim, Woo Joo; Park, Mee Sook; Song, Jin-Won; Kee, Sun-Ho; Song, Ki-Joon; Park, Man-Seong

    2017-01-01

    Seasonal influenza is caused by two influenza A subtype (H1N1 and H3N2) and two influenza B lineage (Victoria and Yamagata) viruses. Of these antigenically distinct viruses, the H3N2 virus was consistently detected in substantial proportions in Korea during the 2010/11-2013/14 seasons when compared to the other viruses and appeared responsible for the influenza-like illness rate peak during the first half of the 2011/12 season. To further scrutinize possible causes for this, we investigated the evolutionary and serological relationships between the vaccine and Korean H3N2 strains during the 2011/12 season for the main antigenic determinants of influenza viruses, the hemagglutinin (HA) and neuraminidase (NA) genes. In the 2011/12 season, when the number of H3N2 cases peaked, the majority of the Korean strains did not belong to the HA clade of A/Perth/16/2009 vaccine, and no Korean strains were of this lineage in the NA segment. In a serological assay, post-vaccinated human sera exhibited much reduced hemagglutination inhibition antibody titers against the non-vaccine clade Korean H3N2 strains. Moreover, Korean strains harbored several amino acid differences in the HA antigenic sites and in the NA with respect to vaccine lineages during this season. Of these, the HA antigenic site C residues 45 and 261 and the NA residue 81 appeared to be the signatures of positive selection. In subsequent seasons, when H3N2 cases were lower, the HA and NA genes of vaccine and Korean strains were more phylogenetically related to each other. Combined, our results provide indirect support for using phylogenetic clustering patterns of the HA and possibly also the NA genes in the selection of vaccine viruses and the assessment of vaccine effectiveness. PMID:28257427

  10. Avian influenza virus (H5N1): a threat to human health.

    PubMed

    Peiris, J S Malik; de Jong, Menno D; Guan, Yi

    2007-04-01

    Pandemic influenza virus has its origins in avian influenza viruses. The highly pathogenic avian influenza virus subtype H5N1 is already panzootic in poultry, with attendant economic consequences. It continues to cross species barriers to infect humans and other mammals, often with fatal outcomes. Therefore, H5N1 virus has rightly received attention as a potential pandemic threat. However, it is noted that the pandemics of 1957 and 1968 did not arise from highly pathogenic influenza viruses, and the next pandemic may well arise from a low-pathogenicity virus. The rationale for particular concern about an H5N1 pandemic is not its inevitability but its potential severity. An H5N1 pandemic is an event of low probability but one of high human health impact and poses a predicament for public health. Here, we review the ecology and evolution of highly pathogenic avian influenza H5N1 viruses, assess the pandemic risk, and address aspects of human H5N1 disease in relation to its epidemiology, clinical presentation, pathogenesis, diagnosis, and management.

  11. [Trends in and challenges for highly pathogenic avian influenza A (H5N1)].

    PubMed

    Kudo, Koichiro; Manabe, Toshie; Izumi, Shinyu; Takasaki, Jin

    2010-09-01

    A new pandemic influenza A (H1N1) virus had emerged and rapidly spread throughout the world. The clinical pathological observations associated with severe cases of pandemic (H1N1) 2009 are similar to that of high pathogenic avian influenza (H5N1). In order to find the most effective treatment methods for this pandemic influenza (H1N1), we describe our experiences, investigations and collaboration studies of avian influenza (H5N1) in Vietnam in association of our cooperative study of pandemic (H1N1) 2009 in Mexico. Effective treatment methods for critical illness due to influenza will be discussed from medical, regional and global points of view, which may be applied for the treatment of any type of influenza virus.

  12. Observational study to investigate vertically acquired passive immunity in babies of mothers vaccinated against H1N1v during pregnancy.

    PubMed

    Puleston, R L; Bugg, G; Hoschler, K; Konje, J; Thornton, J; Stephenson, I; Myles, P; Enstone, J; Augustine, G; Davis, Y; Zambon, M; Nicholson, K G; Nguyen-Van-Tam, J S

    2010-12-01

    The primary objective was to determine the proportion of babies who acquired passive immunity to A/H1N1v, born to mothers who accepted vaccination as part of the national vaccination programme while pregnant (during the second and/or third trimesters) against the novel A/H1N1v influenza virus (exposed group) compared with unvaccinated (unexposed) mothers. An observational study at three sites in the UK. The purpose was to determine if mothers immunised against A/H1N1v during the pandemic vaccination period transferred that immunity to their child in utero. Three sites in the UK [Queen's Medical Centre, Nottingham; City Hospital, Nottingham (both forming University Hospitals Nottingham), and Leicester Royal Infirmary (part of University Hospitals Leicester)]. All pregnant women in the second and third trimester presenting at the NHS hospitals above to deliver were eligible to participate in the study. Women were included regardless of age, social class, ethnicity, gravida and parity status, past and current medical history (including current medications), ethnicity, mode of delivery and pregnancy outcome (live/stillbirth). At enrolment, participants provided written consent and completed a questionnaire. At parturition, venous cord blood was obtained for serological antibody analysis. Serological analysis was undertaken by the Respiratory Virus Unit (RVU), Health Protection Agency (HPA) Centre for Infections, London. The primary end point in the study was the serological results of the cord blood samples for immunity to A/H1N1v. Regarding a suitable threshold for the determination of a serological response consistent with clinical protection, this issue is somewhat complex for pandemic influenza. The European Medicines Agency (EMEA) Committee for Human Medicinal Products (CHMP) judges that a haemagglutination inhibition (HI) titre of 1 : 40 is an acceptable threshold. However, this level was set in the context of licensing plain trivalent seasonal vaccine, where

  13. Structural Characterization of the 1918 Influenza H1N1 Neuraminidase

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Xu, X.; Zhu, X.; Dwek, R.A.

    2009-05-28

    Influenza virus neuraminidase (NA) plays a crucial role in facilitating the spread of newly synthesized virus in the host and is an important target for controlling disease progression. The NA crystal structure from the 1918 'Spanish flu' (A/Brevig Mission/1/18 H1N1) and that of its complex with zanamivir (Relenza) at 1.65-{angstrom} and 1.45-{angstrom} resolutions, respectively, corroborated the successful expression of correctly folded NA tetramers in a baculovirus expression system. An additional cavity adjacent to the substrate-binding site is observed in N1, compared to N2 and N9 NAs, including H5N1. This cavity arises from an open conformation of the 150 loop (Gly147more » to Asp151) and appears to be conserved among group 1 NAs (N1, N4, N5, and N8). It closes upon zanamivir binding. Three calcium sites were identified, including a novel site that may be conserved in N1 and N4. Thus, these high-resolution structures, combined with our recombinant expression system, provide new opportunities to augment the limited arsenal of therapeutics against influenza.« less

  14. Possible Increased Pathogenicity of Pandemic (H1N1) 2009 Influenza Virus upon Reassortment

    PubMed Central

    Schrauwen, Eefje J.A.; Herfst, Sander; Chutinimitkul, Salin; Bestebroer, Theo M.; Rimmelzwaan, Guus F.; Osterhaus, Albert D.M.E.; Kuiken, Thijs

    2011-01-01

    Since emergence of the pandemic (H1N1) 2009 virus in April 2009, three influenza A viruses—seasonal (H3N2), seasonal (H1N1), and pandemic (H1N1) 2009—have circulated in humans. Genetic reassortment between these viruses could result in enhanced pathogenicity. We compared 4 reassortant viruses with favorable in vitro replication properties with the wild-type pandemic (H1N1) 2009 virus with respect to replication kinetics in vitro and pathogenicity and transmission in ferrets. Pandemic (H1N1) 2009 viruses containing basic polymerase 2 alone or in combination with acidic polymerase of seasonal (H1N1) virus were attenuated in ferrets. In contrast, pandemic (H1N1) 2009 with neuraminidase of seasonal (H3N2) virus resulted in increased virus replication and more severe pulmonary lesions. The data show that pandemic (H1N1) 2009 virus has the potential to reassort with seasonal influenza viruses, which may result in increased pathogenicity while it maintains the capacity of transmission through aerosols or respiratory droplets. PMID:21291589

  15. Natural co-infection of influenza A/H3N2 and A/H1N1pdm09 viruses resulting in a reassortant A/H3N2 virus.

    PubMed

    Rith, Sareth; Chin, Savuth; Sar, Borann; Y, Phalla; Horm, Srey Viseth; Ly, Sovann; Buchy, Philippe; Dussart, Philippe; Horwood, Paul F

    2015-12-01

    Despite annual co-circulation of different subtypes of seasonal influenza, co-infections between different viruses are rarely detected. These co-infections can result in the emergence of reassortant progeny. We document the detection of an influenza co-infection, between influenza A/H3N2 with A/H1N1pdm09 viruses, which occurred in a 3 year old male in Cambodia during April 2014. Both viruses were detected in the patient at relatively high viral loads (as determined by real-time RT-PCR CT values), which is unusual for influenza co-infections. As reassortment can occur between co-infected influenza A strains we isolated plaque purified clonal viral populations from the clinical material of the patient infected with A/H3N2 and A/H1N1pdm09. Complete genome sequences were completed for 7 clonal viruses to determine if any reassorted viruses were generated during the influenza virus co-infection. Although most of the viral sequences were consistent with wild-type A/H3N2 or A/H1N1pdm09, one reassortant A/H3N2 virus was isolated which contained an A/H1N1pdm09 NS1 gene fragment. The reassortant virus was viable and able to infect cells, as judged by successful passage in MDCK cells, achieving a TCID50 of 10(4)/ml at passage number two. There is no evidence that the reassortant virus was transmitted further. The co-infection occurred during a period when co-circulation of A/H3N2 and A/H1N1pdm09 was detected in Cambodia. It is unclear how often influenza co-infections occur, but laboratories should consider influenza co-infections during routine surveillance activities. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

  16. The Swedish A(H1N1) vaccination campaign--why did not all Swedes take the vaccination?

    PubMed

    Björkman, Ingeborg; Sanner, Margareta A

    2013-01-01

    In Sweden, a mass vaccination campaign against the influenza A(H1N1) 2009 resulted in 60% vaccination coverage. However, many countries had difficulty in motivating citizens to be vaccinated. To be prepared for future vaccination campaigns, it is important to understand people's reasons for not taking the vaccination. The aim of this qualitative study was to explore motives, beliefs and reactions of individuals with varying backgrounds who did not get vaccinated. The total 28 individuals participating in the interviews were permitted to speak freely about their experiences and ideas about the vaccination. Interviews were analysed using a Grounded Theory approach. The strength of participants' decisions not to be vaccinated was also estimated. Patterns of motives were identified and described in five main categories: (A) distinguishing between unnecessary and necessary vaccination, (B) distrust, (C) the idea of the natural, (D) resisting an exaggerated safety culture, and (E) injection fear. The core category, upholding autonomy and own health, constitutes the base on which the decisions were grounded. A prerequisite for taking the vaccine would be that people feel involved in the vaccination enterprise to make a sensible decision regarding whether their health will be best protected by vaccination. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  17. The influence of the multi-basic cleavage site of the H5 hemagglutinin on the attenuation, immunogenicity and efficacy of a live attenuated influenza A H5N1 cold-adapted vaccine virus

    PubMed Central

    Suguitan, Amorsolo L.; Marino, Michael P.; Desai, Purvi D.; Chen, Li-Mei; Matsuoka, Yumiko; Donis, Ruben O.; Jin, Hong; Swayne, David E.; Kemble, George; Subbarao, Kanta

    2009-01-01

    A recombinant live attenuated influenza virus ΔH5N1 vaccine with a modified hemagglutinin (HA) and intact neuraminidase genes from A/Vietnam/1203/04 (H5N1) and six remaining genome segments from A/Ann Arbor/6/60 (H2N2) cold-adapted (AA ca) virus was previously shown to be attenuated in chickens, mice and ferrets. Evaluation of the recombinant H5N1 viruses in mice indicated that three independent factors contributed to the attenuation of the ΔH5N1 vaccine: the attenuating mutations specified by the AA ca loci had the greatest influence, followed by the deletion of the H5 HA multi-basic cleavage site (MBS), and the constellation effects of the AA genes acting in concert with the H5N1 glycoproteins. Restoring the MBS in the H5 HA of the vaccine virus improved its immunogenicity and efficacy, likely as a consequence of increased virus replication, indicating that removal of the MBS had a deleterious effect on the immunogenicity and efficacy of the ΔH5N1 vaccine in mice. PMID:19833372

  18. The influence of the multi-basic cleavage site of the H5 hemagglutinin on the attenuation, immunogenicity and efficacy of a live attenuated influenza A H5N1 cold-adapted vaccine virus.

    PubMed

    Suguitan, Amorsolo L; Marino, Michael P; Desai, Purvi D; Chen, Li-Mei; Matsuoka, Yumiko; Donis, Ruben O; Jin, Hong; Swayne, David E; Kemble, George; Subbarao, Kanta

    2009-12-20

    A recombinant live attenuated influenza virus DeltaH5N1 vaccine with a modified hemagglutinin (HA) and intact neuraminidase genes from A/Vietnam/1203/04 (H5N1) and six remaining genome segments from A/Ann Arbor/6/60 (H2N2) cold-adapted (AA ca) virus was previously shown to be attenuated in chickens, mice and ferrets. Evaluation of the recombinant H5N1 viruses in mice indicated that three independent factors contributed to the attenuation of the DeltaH5N1 vaccine: the attenuating mutations specified by the AA ca loci had the greatest influence, followed by the deletion of the H5 HA multi-basic cleavage site (MBS), and the constellation effects of the AA genes acting in concert with the H5N1 glycoproteins. Restoring the MBS in the H5 HA of the vaccine virus improved its immunogenicity and efficacy, likely as a consequence of increased virus replication, indicating that removal of the MBS had a deleterious effect on the immunogenicity and efficacy of the DeltaH5N1 vaccine in mice.

  19. Characterization of a newly emerged genetic cluster of H1N1 and H1N2 swine influenza virus in the United States.

    PubMed

    Vincent, Amy L; Ma, Wenjun; Lager, Kelly M; Gramer, Marie R; Richt, Juergen A; Janke, Bruce H

    2009-10-01

    H1 influenza A viruses that were distinct from the classical swine H1 lineage were identified in pigs in Canada in 2003–2004; antigenic and genetic characterization identified the hemagglutinin (HA) as human H1 lineage. The viruses identified in Canadian pigs were human lineage in entirety or double (human–swine) reassortants. Here, we report the whole genome sequence analysis of four human-like H1 viruses isolated from U.S. swine in 2005 and 2007. All four isolates were characterized as triple reassortants with an internal gene constellation similar to contemporary U.S. swine influenza virus (SIV), with HA and neuraminidase (NA) most similar to human influenza virus lineages. A 2007 human-like H1N1 was evaluated in a pathogenesis and transmission model and compared to a 2004 reassortant H1N1 SIV isolate with swine lineage HA and NA. The 2007 isolate induced disease typical of influenza virus and was transmitted to contact pigs; however, the kinetics and magnitude differed from the 2004 H1N1 SIV. This study indicates that the human-like H1 SIV can efficiently replicate and transmit in the swine host and now co-circulates with contemporary SIVs as a distinct genetic cluster of H1 SIV.

  20. Retrospective Investigation of an Influenza A/H1N1pdm Outbreak in an Italian Military Ship Cruising in the Mediterranean Sea, May-September 2009

    PubMed Central

    Tarabbo, Mario; Lapa, Daniele; Castilletti, Concetta; Tommaselli, Pietro; Guarducci, Riccardo; Lucà, Giuditta; Emanuele, Alessandro; Zaccaria, Onofrio; La Gioia, Vincenzo F. P.; Girardi, Enrico; Capobianchi, Maria R.; Ippolito, Giuseppe

    2011-01-01

    Background Clinical surveillance may have underestimated the real extent of the spread of the new strain of influenza A/H1N1, which surfaced in April 2009 originating the first influenza pandemic of the 21st century. Here we report a serological investigation on an influenza A/H1N1pdm outbreak in an Italian military ship while cruising in the Mediterranean Sea (May 24-September 6, 2009). Methods The contemporary presence of HAI and CF antibodies was used to retrospectively estimate the extent of influenza A/H1N1pdm spread across the crew members (median age: 29 years). Findings During the cruise, 2 crew members fulfilled the surveillance case definition for influenza, but only one was laboratory confirmed by influenza A/H1N1pdm-specific RT-PCR; 52 reported acute respiratory illness (ARI) episodes, and 183 reported no ARI episodes. Overall, among the 211 crew member for whom a valid serological result was available, 39.3% tested seropositive for influenza A/H1N1pdm. The proportion of seropositives was significantly associated with more crowded living quarters and tended to be higher in those aged <40 and in those reporting ARI or suspected/confirmed influenza A/H1N1pdm compared to the asymptomatic individuals. No association was found with previous seasonal influenza vaccination. Conclusions These findings underline the risk for rapid spread of novel strains of influenza A in confined environment, such as military ships, where crowding, rigorous working environment, physiologic stress occur. The high proportion of asymptomatic infections in this ship-borne outbreak supports the concept that serological surveillance in such semi-closed communities is essential to appreciate the real extent of influenza A/H1N1pdm spread and can constitute, since the early stage of a pandemic, an useful model to predict the public health impact of pandemic influenza and to establish proportionate and effective countermeasures. PMID:21283749

  1. [Results of clinical trials on reactogenicity, safety, and immunogenicity of influenza allantoic intranasal live vaccine "Ultragrivac" (type A/H5N2)].

    PubMed

    Mazurkova, N A; Ryndiuk, N N; Shishkina, L N; Ternovoĭ, V A; Tumanov, Iu V; Bulychev, L E; Skarnovich, M O; Kabanov, A S; Panchenko, S G; Aleĭnikov, R P; Il'ina, T N; Kuzubov, V I; Mel'nikov, S Ia; Mironov, A N; Korovkin, S A; Sergeev, A N; Drozdov, I G

    2010-01-01

    Results of phase II of a clinical trial of the influenza allantoic intranasal live vaccine "Ultragrivac" (type A/H5N2) are presented. The vaccine was developed based on strain /17/Duck/Potsdam/86/92 H5N2 [17/H5] - reassortant of two viruses, /Leningrad/134/17/57 (H2N2) and /Duck/Potsdam/1402-86 (H5N2), obtained from the Virology Department, St. Petersburg Institute of Experimental Medicine.Two schemes of immunization (with revaccination on days 10 and 21) were used. Evaluation of vaccine immunogenicity included determination of local, cellular and humoral immunity. A significant rise in the level of secretory IgA in the nasal cavity of vaccinated volunteers (with revaccination on days 10 and 21) was documented after application of the vaccine. The postvaccination humoral immune response was estimated from the level of significant (4-fold and more) antibody seroconversions, geometric mean titers of antibodies to two strains of influenza virus /17/Duck/Potsdam/86/92 H5N2 [17/H5] and /Chicken/Suzdalka/Nov-11/2005 (H5N1), and their incremental rate. Results of measurement of antibody titers in hemagglutination-inhibition assay are presented, with two antigens being used to analyse all serum samples from volunteers twice vaccinated with influenza vaccine "Ultragrivac" at 10 and 21 day intervals. Result of phase II of this clinical study show that influenza allantoic intranasal live vaccine "Ultragrivac" is nonreactogenic and safe for both vaccinated and surrounding individuals. Moreover, it is sufficiently immunogenic with respect not only to homologous virus A(H5N2) but also to the A(H5N1) strain.

  2. Experimental infection of clade 1.1.2 (H5N1), clade 2.3.2.1c (H5N1) and clade 2.3.4.4 (H5N6) highly pathogenic avian influenza viruses in dogs.

    PubMed

    Lyoo, K S; Na, W; Phan, L V; Yoon, S W; Yeom, M; Song, D; Jeong, D G

    2017-12-01

    Since the emergence of highly pathogenic avian influenza (HPAI) H5N1 in Asia, the haemagglutinin (HA) gene of this virus lineage has continued to evolve in avian populations, and H5N1 lineage viruses now circulate concurrently worldwide. Dogs may act as an intermediate host, increasing the potential for zoonotic transmission of influenza viruses. Virus transmission and pathologic changes in HPAI clade 1.1.2 (H5N1)-, 2.3.2.1c (H5N1)- and 2.3.4.4 (H5N6)-infected dogs were investigated. Mild respiratory signs and antibody response were shown in dogs intranasally infected with the viruses. Lung histopathology showed lesions that were associated with moderate interstitial pneumonia in the infected dogs. In this study, HPAI H5N6 virus replication in dogs was demonstrated for the first time. Dogs have been suspected as a "mixing vessel" for reassortments between avian and human influenza viruses to occur. The replication of these three subtypes of the H5 lineage of HPAI viruses in dogs suggests that dogs could serve as intermediate hosts for avian-human influenza virus reassortment if they are also co-infected with human influenza viruses. © 2017 Blackwell Verlag GmbH.

  3. Critical illness in children with influenza A/pH1N1 2009 infection in Canada.

    PubMed

    Jouvet, Philippe; Hutchison, Jamie; Pinto, Ruxandra; Menon, Kusum; Rodin, Rachel; Choong, Karen; Kesselman, Murray; Veroukis, Stasa; André Dugas, Marc; Santschi, Miriam; Guerguerian, Anne-Marie; Withington, Davinia; Alsaati, Basem; Joffe, Ari R; Drews, Tanya; Skippen, Peter; Rolland, Elizabeth; Kumar, Anand; Fowler, Robert

    2010-09-01

    To describe characteristics, treatment, and outcomes of critically ill children with influenza A/pandemic influenza A virus (pH1N1) infection in Canada. An observational study of critically ill children with influenza A/pH1N1 infection in pediatric intensive care units (PICUs). Nine Canadian PICUs. A total of 57 patients admitted to PICUs between April 16, 2009 and August 15, 2009. None. Characteristics of critically ill children with influenza A/pH1N1 infection were recorded. Confirmed intensive care unit cases were compared with a national surveillance database containing all hospitalized pediatric patients with influenza A/pH1N1 infection. Risk factors were assessed with a Cox proportional hazard model. The PICU cohort and national surveillance data were compared, using chi-square tests. Fifty-seven children were admitted to the PICU for community-acquired influenza A/pH1N1 infection. One or more chronic comorbid illnesses were observed in 70.2% of patients, and 24.6% of patients were aboriginal. Mechanical ventilation was used in 68% of children, 20 children (35.1%) had acute lung injury on the first day of admission, and the median duration of ventilation was 6 days (range, 0-67 days). The PICU mortality rate was 7% (4 of 57 patients). When compared with nonintensive care unit hospitalized children, PICU children were more likely to have a chronic medical condition (relative risk, 1.73); aboriginal ethnicity was not a risk factor of intensive care unit admission. During the first outbreak of influenza A/pH1N1 infection, when the population was naïve to this novel virus, severe illness was common among children with underlying chronic conditions and aboriginal children. Influenza A/pH1N1-related critical illness in children was associated with severe hypoxemic respiratory failure and prolonged mechanical ventilation. However, this higher rate and severity of respiratory illness did not result in an increased mortality when compared with seasonal influenza.

  4. Genetic Characterization of H1N1 and H1N2 Influenza A Viruses Circulating in Ontario Pigs in 2012.

    PubMed

    Grgić, Helena; Costa, Marcio; Friendship, Robert M; Carman, Susy; Nagy, Éva; Poljak, Zvonimir

    2015-01-01

    The objective of this study was to characterize H1N1 and H1N2 influenza A virus isolates detected during outbreaks of respiratory disease in pig herds in Ontario (Canada) in 2012. Six influenza viruses were included in analysis using full genome sequencing based on the 454 platform. In five H1N1 isolates, all eight segments were genetically related to 2009 pandemic virus (A(H1N1)pdm09). One H1N2 isolate had hemagglutinin (HA), polymerase A (PA) and non-structural (NS) genes closely related to A(H1N1)pdm09, and neuraminidase (NA), matrix (M), polymerase B1 (PB1), polymerase B2 (PB2), and nucleoprotein (NP) genes originating from a triple-reassortant H3N2 virus (tr H3N2). The HA gene of five Ontario H1 isolates exhibited high identity of 99% with the human A(H1N1)pdm09 [A/Mexico/InDRE4487/09] from Mexico, while one Ontario H1N1 isolate had only 96.9% identity with this Mexican virus. Each of the five Ontario H1N1 viruses had between one and four amino acid (aa) changes within five antigenic sites, while one Ontario H1N2 virus had two aa changes within two antigenic sites. Such aa changes in antigenic sites could have an effect on antibody recognition and ultimately have implications for immunization practices. According to aa sequence analysis of the M2 protein, Ontario H1N1 and H1N2 viruses can be expected to offer resistance to adamantane derivatives, but not to neuraminidase inhibitors.

  5. An avian influenza H5N1 virus vaccine candidate based on the extracellular domain produced in yeast system as subviral particles protects chickens from lethal challenge.

    PubMed

    Pietrzak, Maria; Macioła, Agnieszka; Zdanowski, Konrad; Protas-Klukowska, Anna Maria; Olszewska, Monika; Śmietanka, Krzysztof; Minta, Zenon; Szewczyk, Bogusław; Kopera, Edyta

    2016-09-01

    Highly pathogenic avian influenza is an on-going problem in poultry and a potential human pandemic threat. Pandemics occur suddenly and vaccine production must be fast and effective to be of value in controlling the spread of the virus. In this study we evaluated the potential of a recombinant protein from the extracellular domain of an H5 hemagglutinin protein produced in a yeast expression system to act as an effective vaccine. Protein production was efficient, with up to 200 mg purified from 1 L of culture medium. We showed that the deletion of the multibasic cleavage site from the protein improves oligomerization and, consequentially, its immunogenicity. We also showed that immunization with this deleted protein protected chickens from challenge with a highly pathogenic avian influenza H5N1 virus. Our results suggest that this recombinant protein produced in yeast may be an effective vaccine against H5N1 virus in poultry. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  6. A DNA Vaccine That Targets Hemagglutinin to Antigen-Presenting Cells Protects Mice against H7 Influenza

    PubMed Central

    Andersen, Tor Kristian; Zhou, Fan; Cox, Rebecca; Bogen, Bjarne

    2017-01-01

    ABSTRACT Zoonotic influenza H7 viral infections have a case fatality rate of about 40%. Currently, no or limited human to human spread has occurred, but we may be facing a severe pandemic threat if the virus acquires the ability to transmit between humans. Novel vaccines that can be rapidly produced for global distribution are urgently needed, and DNA vaccines may be the only type of vaccine that allows for the speed necessary to quench an emerging pandemic. Here, we constructed DNA vaccines encoding the hemagglutinin (HA) from influenza A/chicken/Italy/13474/99 (H7N1). In order to increase the efficacy of DNA vaccination, HA was targeted to either major histocompatibility complex class II molecules or chemokine receptors 1, 3, and 5 (CCR1/3/5) that are expressed on antigen-presenting cells (APC). A single DNA vaccination with APC-targeted HA significantly increased antibody levels in sera compared to nontargeted control vaccines. The antibodies were confirmed neutralizing in an H7 pseudotype-based neutralization assay. Furthermore, the APC-targeted vaccines increased the levels of antigen-specific cytotoxic T cells, and a single DNA vaccination could confer protection against a lethal challenge with influenza A/turkey/Italy/3889/1999 (H7N1) in mice. In conclusion, we have developed a vaccine that rapidly could contribute protection against a pandemic threat from avian influenza. IMPORTANCE Highly pathogenic avian influenza H7 constitute a pandemic threat that can cause severe illness and death in infected individuals. Vaccination is the main method of prophylaxis against influenza, but current vaccine strategies fall short in a pandemic situation due to a prolonged production time and insufficient production capabilities. In contrast, a DNA vaccine can be rapidly produced and deployed to prevent the potential escalation of a highly pathogenic influenza pandemic. We here demonstrate that a single DNA delivery of hemagglutinin from an H7 influenza could mediate full

  7. Antibody Immunity Induced by H7N9 Avian Influenza Vaccines: Evaluation Criteria, Affecting Factors, and Implications for Rational Vaccine Design

    PubMed Central

    Hu, Zenglei; Jiao, Xinan; Liu, Xiufan

    2017-01-01

    Severe H7N9 avian influenza virus (AIV) infections in humans have public health authorities around the world on high alert for the potential development of a human influenza pandemic. Currently, the newly-emerged highly pathogenic avian influenza A (H7N9) virus poses a dual challenge for public health and poultry industry. Numerous H7N9 vaccine candidates have been generated using various platforms. Immunization trials in animals and humans showed that H7N9 vaccines are apparently poorly immunogenic because they induced low hemagglutination inhibition and virus neutralizing antibody titers. However, H7N9 vaccines elicit comparable levels of total hemagglutinin (HA)-reactive IgG antibody as the seasonal influenza vaccines, suggesting H7N9 vaccines are as immunogenic as their seasonal counterparts. A large fraction of overall IgG antibody is non-neutralizing antibody and they target unrecognized epitopes outside of the traditional antigenic sites in HA. Further, the Treg epitope identified in H7 HA may at least partially contribute to regulation of antibody immunity. Here, we review the latest advances for the development of H7N9 vaccines and discuss the influence of serological criteria on evaluation of immunogenicity of H7N9 vaccines. Next, we discuss factors affecting antibody immunity induced by H7N9 vaccines, including the change in antigenic epitopes in HA and the presence of the Treg epitope. Last, we present our perspectives for the unique features of antibody immunity of H7N9 vaccines and propose some future directions to improve or modify antibody response induced by H7N9 vaccines. This perspective would provide critical implications for rational design of H7N9 vaccines for human and veterinary use. PMID:29018438

  8. Identification of Amino Acid Substitutions Supporting Antigenic Change of Influenza A(H1N1)pdm09 Viruses

    PubMed Central

    Koel, Björn F.; Mögling, Ramona; Chutinimitkul, Salin; Fraaij, Pieter L.; Burke, David F.; van der Vliet, Stefan; de Wit, Emmie; Bestebroer, Theo M.; Rimmelzwaan, Guus F.; Osterhaus, Albert D. M. E.; Smith, Derek J.; Fouchier, Ron A. M.

    2015-01-01

    ABSTRACT The majority of currently circulating influenza A(H1N1) viruses are antigenically similar to the virus that caused the 2009 influenza pandemic. However, antigenic variants are expected to emerge as population immunity increases. Amino acid substitutions in the hemagglutinin protein can result in escape from neutralizing antibodies, affect viral fitness, and change receptor preference. In this study, we constructed mutants with substitutions in the hemagglutinin of A/Netherlands/602/09 in an attenuated backbone to explore amino acid changes that may contribute to emergence of antigenic variants in the human population. Our analysis revealed that single substitutions affecting the loop that consists of amino acid positions 151 to 159 located adjacent to the receptor binding site caused escape from ferret and human antibodies elicited after primary A(H1N1)pdm09 virus infection. The majority of these substitutions resulted in similar or increased replication efficiency in vitro compared to that of the virus carrying the wild-type hemagglutinin and did not result in a change of receptor preference. However, none of the substitutions was sufficient for escape from the antibodies in sera from individuals that experienced both seasonal and pandemic A(H1N1) virus infections. These results suggest that antibodies directed against epitopes on seasonal A(H1N1) viruses contribute to neutralization of A(H1N1)pdm09 antigenic variants, thereby limiting the number of possible substitutions that could lead to escape from population immunity. IMPORTANCE Influenza A viruses can cause significant morbidity and mortality in humans. Amino acid substitutions in the hemagglutinin protein can result in escape from antibody-mediated neutralization. This allows the virus to reinfect individuals that have acquired immunity to previously circulating strains through infection or vaccination. To date, the vast majority of A(H1N1)pdm09 strains remain antigenically similar to the virus

  9. A Duck Enteritis Virus-Vectored Bivalent Live Vaccine Provides Fast and Complete Protection against H5N1 Avian Influenza Virus Infection in Ducks ▿ † §

    PubMed Central

    Liu, Jinxiong; Chen, Pucheng; Jiang, Yongping; Wu, Li; Zeng, Xianying; Tian, Guobin; Ge, Jinying; Kawaoka, Yoshihiro; Bu, Zhigao; Chen, Hualan

    2011-01-01

    Ducks play an important role in the maintenance of highly pathogenic H5N1 avian influenza viruses (AIVs) in nature, and the successful control of AIVs in ducks has important implications for the eradication of the disease in poultry and its prevention in humans. The inactivated influenza vaccine is expensive, labor-intensive, and usually needs 2 to 3 weeks to induce protective immunity in ducks. Live attenuated duck enteritis virus (DEV; a herpesvirus) vaccine is used routinely to control lethal DEV infections in many duck-producing areas. Here, we first established a system to generate the DEV vaccine strain by using the transfection of overlapping fosmid DNAs. Using this system, we constructed two recombinant viruses, rDEV-ul41HA and rDEV-us78HA, in which the hemagglutinin (HA) gene of the H5N1 virus A/duck/Anhui/1/06 was inserted and stably maintained within the ul41 gene or between the us7 and us8 genes of the DEV genome. Duck studies indicated that rDEV-us78HA had protective efficacy similar to that of the live DEV vaccine against lethal DEV challenge; importantly, a single dose of 106 PFU of rDEV-us78HA induced complete protection against a lethal H5N1 virus challenge in as little as 3 days postvaccination. The protective efficacy against both lethal DEV and H5N1 challenge provided by rDEV-ul41HA inoculation in ducks was slightly weaker than that provided by rDEV-us78HA. These results demonstrate, for the first time, that recombinant DEV is suitable for use as a bivalent live attenuated vaccine, providing rapid protection against both DEV and H5N1 virus infection in ducks. PMID:21865383

  10. Predictors of influenza vaccine uptake during the 2009/10 influenza A H1N1v ('swine flu') pandemic: Results from five national surveys in the United Kingdom.

    PubMed

    Han, You Kyung Julia; Michie, Susan; Potts, Henry W W; Rubin, G James

    2016-03-01

    To investigate reasons underlying the low uptake of the influenza A H1N1v vaccination in the UK during the 2009/10 pandemic. We analysed data from five national telephone surveys conducted in the UK during the latter stages of the pandemic to identify predictors of uptake amongst members of the public offered the vaccine by their primary care physician (n=1320). In addition to demographic variables, participants reported: reasons for declining the vaccination, levels of worry about the risk of catching swine flu, whether too much fuss was being made about the pandemic, whether they or a close friend or relative had had swine flu, how effective they felt the vaccine was, whether they had previously had a seasonal flu vaccination, how well prepared they felt the government was for a pandemic and how satisfied they were with information available about the pandemic. Most participants (n=734, 55.6%) reported being vaccinated against swine flu, compared to 396 who had not been vaccinated and were unlikely to be vaccinated in the future. The main reasons given for declining vaccination were concerns over the vaccine's safety, and being generally healthy. Controlling for demographic variables, risk factors for not being vaccinated were: being female, not having a long-standing infirmity or illness, not having been vaccinated against seasonal flu in previous years, feeling that too much fuss had been made about the pandemic and believing that the vaccine was ineffective. Interventions that target these factors may be effective in improving uptake in a future pandemic. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  11. Pandemic and post-pandemic Influenza A (H1N1) infection in critically ill patients

    PubMed Central

    2011-01-01

    Background There is a vast amount of information published regarding the impact of 2009 pandemic Influenza A (pH1N1) virus infection. However, a comparison of risk factors and outcome during the 2010-2011 post-pandemic period has not been described. Methods A prospective, observational, multi-center study was carried out to evaluate the clinical characteristics and demographics of patients with positive RT-PCR for H1N1 admitted to 148 Spanish intensive care units (ICUs). Data were obtained from the 2009 pandemic and compared to the 2010-2011 post-pandemic period. Results Nine hundred and ninety-seven patients with confirmed An/H1N1 infection were included. Six hundred and forty-eight patients affected by 2009 (pH1N1) virus infection and 349 patients affected by the post-pandemic Influenza (H1N1)v infection period were analyzed. Patients during the post-pandemic period were older, had more chronic comorbid conditions and presented with higher severity scores (Acute Physiology And Chronic Health Evaluation II (APACHE II) and Sequential Organ Failure Assessment (SOFA)) on ICU admission. Patients from the post-pandemic Influenza (H1N1)v infection period received empiric antiviral treatment less frequently and with delayed administration. Mortality was significantly higher in the post-pandemic period. Multivariate analysis confirmed that haematological disease, invasive mechanical ventilation and continuous renal replacement therapy were factors independently associated with worse outcome in the two periods. HIV was the only new variable independently associated with higher ICU mortality during the post-pandemic Influenza (H1N1)v infection period. Conclusion Patients from the post-pandemic Influenza (H1N1)v infection period had an unexpectedly higher mortality rate and showed a trend towards affecting a more vulnerable population, in keeping with more typical seasonal viral infection. PMID:22126648

  12. Pandemic and post-pandemic influenza A (H1N1) infection in critically ill patients.

    PubMed

    Martin-Loeches, Ignacio; Díaz, Emili; Vidaur, Loreto; Torres, Antoni; Laborda, Cesar; Granada, Rosa; Bonastre, Juan; Martín, Mar; Insausti, Josu; Arenzana, Angel; Guerrero, Jose Eugenio; Navarrete, Ines; Bermejo-Martin, Jesus; Suarez, David; Rodriguez, Alejandro

    2011-01-01

    There is a vast amount of information published regarding the impact of 2009 pandemic Influenza A (pH1N1) virus infection. However, a comparison of risk factors and outcome during the 2010-2011 post-pandemic period has not been described. A prospective, observational, multi-center study was carried out to evaluate the clinical characteristics and demographics of patients with positive RT-PCR for H1N1 admitted to 148 Spanish intensive care units (ICUs). Data were obtained from the 2009 pandemic and compared to the 2010-2011 post-pandemic period. Nine hundred and ninety-seven patients with confirmed An/H1N1 infection were included. Six hundred and forty-eight patients affected by 2009 (pH1N1) virus infection and 349 patients affected by the post-pandemic Influenza (H1N1)v infection period were analyzed. Patients during the post-pandemic period were older, had more chronic comorbid conditions and presented with higher severity scores (Acute Physiology And Chronic Health Evaluation II (APACHE II) and Sequential Organ Failure Assessment (SOFA)) on ICU admission. Patients from the post-pandemic Influenza (H1N1)v infection period received empiric antiviral treatment less frequently and with delayed administration. Mortality was significantly higher in the post-pandemic period. Multivariate analysis confirmed that haematological disease, invasive mechanical ventilation and continuous renal replacement therapy were factors independently associated with worse outcome in the two periods. HIV was the only new variable independently associated with higher ICU mortality during the post-pandemic Influenza (H1N1)v infection period. Patients from the post-pandemic Influenza (H1N1)v infection period had an unexpectedly higher mortality rate and showed a trend towards affecting a more vulnerable population, in keeping with more typical seasonal viral infection.

  13. Supply of neuraminidase inhibitors related to reduced influenza A (H1N1) mortality during the 2009-2010 H1N1 pandemic: summary of an ecological study.

    PubMed

    Miller, Paula E; Rambachan, Aksharananda; Hubbard, Roderick J; Li, Jiabai; Meyer, Alison E; Stephens, Peter; Mounts, Anthony W; Rolfes, Melissa A; Penn, Charles R

    2013-09-01

    When the influenza A (H1N1) pandemic spread across the globe from April 2009 to August 2010, many WHO Member States used antiviral drugs, specifically neuraminidase inhibitors (NAIs) oseltamivir and zanamivir, to treat influenza patients in critical condition. Antivirals have been found to be effective in reducing severity and duration of influenza illness, and likely reduce morbidity; however, it is unclear whether NAIs used during the pandemic reduced H1N1 mortality. To assess the association between antivirals and influenza mortality, at an ecologic level, country-level data on supply of oseltamivir and zanamivir were compared to laboratory-confirmed H1N1 deaths (per 100 000 people) from July 2009 to August 2010 in 42 WHO Member States. From this analysis, it was found that each 10% increase in kilograms of oseltamivir, per 100 000 people, was associated with a 1·6% reduction in H1N1 mortality over the pandemic period [relative rate (RR) = 0·84 per log increase in oseltamivir supply]. Each 10% increase in kilogram of active zanamivir, per 100 000, was associated with a 0·3% reduction in H1N1 mortality (RR = 0·97 per log increase). While limitations exist in the inference that can be drawn from an ecologic evaluation, this analysis offers evidence of a protective relationship between antiviral drug supply and influenza mortality and supports a role for influenza antiviral use in future pandemics. This article summarises the original study described previously, which can be accessed through the following citation: Miller PE, Rambachan A, Hubbard RJ, Li J, Meyer AE, et al. (2012) Supply of Neuraminidase Inhibitors Related to Reduced Influenza A (H1N1) Mortality during the 2009-2010 H1N1 Pandemic: An Ecological Study. PLoS ONE 7(9): e43491. © 2013 Blackwell Publishing Ltd.

  14. Rapid research response to the 2009 A(H1N1)pdm09 influenza pandemic (Revised)

    PubMed Central

    2013-01-01

    Background When novel influenza viruses cause human infections, it is critical to characterize the illnesses, viruses, and immune responses to infection in order to develop diagnostics, treatments, and vaccines. The objective of the study was to collect samples from patients with suspected or confirmed A(H1N1)pdm09 infections that could be made available to the scientific community. Respiratory secretions, sera and peripheral blood mononuclear cells (PBMCs) were collected sequentially (when possible) from patients presenting with suspected or previously confirmed A(H1N1)pdm09 infections. Clinical manifestations and illness outcomes were assessed. Respiratory secretions were tested for the presence of A(H1N1)pdm09 virus by means of isolation in tissue culture and real time RT-PCR. Sera were tested for the presence and level of HAI and neutralizing antibodies against the A(H1N1)pdm09 virus. Findings and conclusions Thirty patients with confirmed A(H1N1)pdm09 infection were enrolled at Baylor College of Medicine (BCM). Clinical manifestations of illness were consistent with typical influenza. Twenty-eight of 30 had virological confirmation of illness; all recovered fully. Most patients had serum antibody responses or high levels of antibody in convalescent samples. Virus-positive samples were sent to J. Craig Venter Institute for sequencing and sequences were deposited in GenBank. Large volumes of sera collected from 2 convalescent adults were used to standardize antibody assays; aliquots of these sera are available from the repository. Aliquots of serum, PBMCs and stool collected from BCM subjects and subjects enrolled at other study sites are available for use by the scientific community, upon request. PMID:23641940

  15. Cardiac complications associated with the influenza viruses A subtype H7N9 or pandemic H1N1 in critically ill patients under intensive care.

    PubMed

    Wang, Jiajia; Xu, Hua; Yang, Xinjing; Zhao, Daguo; Liu, Shenglan; Sun, Xue; Huang, Jian-An; Guo, Qiang

    The clinical presentations and disease courses of patients hospitalized with either influenza A virus subtype H7N9 (H7N9) or 2009 pandemic H1N1 influenza virus were compared in a recent report, but associated cardiac complications remain unclear. The present retrospective study investigated whether cardiac complications in critically ill patients with H7N9 infections differed from those infected with the pandemic H1N1 influenza virus strain. Suspect cases were confirmed by reverse transcription polymerase chain reaction assays with specific confirmation of the pandemic H1N1 strain at the Centers for Disease Control and Prevention. Comparisons were conducted at the individual-level data of critically ill patients hospitalized with H7N9 (n=24) or pandemic H1N1 influenza virus (n=22) infections in Suzhou, China. Changes in cardiac biochemical markers, echocardiography, and electrocardiography during hospitalization in the intensive care unit were considered signs of cardiac complications. The following findings were more common among the H7N9 group relative to the pandemic H1N1 influenza virus group: greater tricuspid regurgitation pressure gradient, sinus tachycardia (heartbeat≥130bpm), ST segment depression, right ventricular dysfunction, and elevated cardiac biochemical markers. Pericardial effusion was more often found among pandemic H1N1 influenza virus patients than in the H7N9 group. In both groups, most of the cardiac complications were detected from day 6 to 14 after the onset of influenza symptoms. Those who developed cardiac complications were especially vulnerable during the first four days after initiation of mechanical ventilation. Cardiac complications were reversible in the vast majority of discharged H7N9 patients. Critically ill hospitalized H7N9 patients experienced a higher rate of cardiac complications than did patients with 2009 pandemic H1N1 influenza virus infections, with the exception of pericardial effusion. This study may help in the

  16. Influenza vaccination among pregnant women--Massachusetts, 2009-2010.

    PubMed

    2013-11-01

    The emergence of the novel influenza A (H1N1) pdm09 (pH1N1) strain in 2009 required a coordinated public health response, especially among high-risk populations. Because pregnant women were at increased risk for influenza-related complications and hospitalization compared with the general population, the American College of Obstetricians and Gynecologists and the Advisory Committee on Immunization Practices recommended pregnant women receive both the pH1N1 vaccine and the annual seasonal vaccine during the 2009-10 influenza season as a safe and effective way of protecting both mother and infant. To describe acceptance, predictors, and barriers to influenza vaccination among pregnant women in Massachusetts during the 2009-10 influenza season, the Massachusetts Department of Public Health (MDPH) analyzed data from supplemental influenza questions on the Massachusetts Pregnancy Risk Assessment Monitoring System (PRAMS) survey. The results indicated that 67.5% of residents who had live births in Massachusetts during September 2009-May 2010 received the seasonal vaccine, and 57.6% received the pH1N1 vaccine. Women who were non-Hispanic blacks, aged <25 years, Medicaid beneficiaries, or lived in a household with an income at or below the federal poverty level were significantly less likely to receive the seasonal vaccine. For the pH1N1 vaccine, only being non-Hispanic black was associated with being less likely to have been vaccinated. Vaccination rates were significantly higher among women whose provider offered or recommended the seasonal (75.8%) and pH1N1 (68.1%) vaccines compared with those who did not receive a recommendation (32.4% and 8.6%, respectively). Coverage in Massachusetts was among the highest of 29 PRAMS sites and might have reflected strategic efforts by MDPH to support vaccine education and equity across the state.

  17. Liver Biochemistry During the Course of Influenza A/H1N1 Infection.

    PubMed

    Seretis, Charalampos; Lagoudianakis, Emmanuel; Salemis, Nikolaos; Pappas, Apostolos; Gemenetzis, George; Seretis, Fotios; Gourgiotis, Stavros

    2013-06-01

    Despite the multi-systemic effects of influenza A/H1N1 virus, the occurrence of hepatic injury during the natural course of the infection remains a matter of debate. We performed a review of the published clinical studies which assess the above mentioned relationship, reviewing the studies published in PubMed database (English literature), using the key words "H1N1", "influenza A" and "liver". We excluded case reports and clinical studies that referred to pediatric and transplanted patients, pregnants and patients with known history of chronic liver diseases. From a total of 96 results, a total of 78 papers met one or more of the exclusion criteria set. Evaluating the remaining 18 published papers, 14 more were excluded as they did not provide any sufficient data, relevant to the subject of our review. Although the analysis of the remaining studies revealed the existence of conflicting results concerning the exact degree and the potential mechanisms of liver injury in H1N1 positive patients, it can be assumed that influenza A/H1N1 virus is -or at least could be- a hepatotropic virus.

  18. Liver Biochemistry During the Course of Influenza A/H1N1 Infection

    PubMed Central

    Seretis, Charalampos; Lagoudianakis, Emmanuel; Salemis, Nikolaos; Pappas, Apostolos; Gemenetzis, George; Seretis, Fotios; Gourgiotis, Stavros

    2013-01-01

    Despite the multi-systemic effects of influenza A/H1N1 virus, the occurrence of hepatic injury during the natural course of the infection remains a matter of debate. We performed a review of the published clinical studies which assess the above mentioned relationship, reviewing the studies published in PubMed database (English literature), using the key words “H1N1”, “influenza A” and “liver”. We excluded case reports and clinical studies that referred to pediatric and transplanted patients, pregnants and patients with known history of chronic liver diseases. From a total of 96 results, a total of 78 papers met one or more of the exclusion criteria set. Evaluating the remaining 18 published papers, 14 more were excluded as they did not provide any sufficient data, relevant to the subject of our review. Although the analysis of the remaining studies revealed the existence of conflicting results concerning the exact degree and the potential mechanisms of liver injury in H1N1 positive patients, it can be assumed that influenza A/H1N1 virus is -or at least could be- a hepatotropic virus. PMID:27785237

  19. Impact of influenza in the post-pandemic phase: Clinical features in hospitalized patients with influenza A (H1N1) pdm09 and H3N2 viruses, during 2013 in Santa Fe, Argentina.

    PubMed

    Kusznierz, Gabriela; Carolina, Cudós; Manuel, Rudi Juan; Sergio, Lejona; Lucila, Ortellao; Julio, Befani; Mirta, Villani; Pedro, Morana; Graciana, Morera; Andrea, Uboldi; Elsa, Zerbini

    2017-07-01

    It is important to characterize the clinical and epidemiological pattern of the influenza A (H1N1) pdm09 virus and compare it with influenza A (H3N2) virus, as surveyed in just a few studies, in order to contribute to the implementation and strengthening of influenza control and prevention strategies. The aims in this study were to describe influenza clinical and epidemiological characteristics in hospitalized patients, caused by influenza A (H1N1)pdm09 and influenza A (H3N2) viruses during 2013, in Santa Fe, Argentina. A retrospective study was conducted over 2013 among hospitalized patients with laboratory-confirmed influenza diagnosis. In contrast to patients with influenza A (H3N2) (20.5%), a higher proportion of hospitalizations associated with influenza H1N1pdm were reported among adults aged 35-65 years (42.8%). Of all patients, 73.6% had an underlying medical condition. Hospitalized patients with H1N1pdm were subject to 2.6 (95%CI, 1.0-6.8) times higher risk of severity, than those hospitalized with influenza A (H3N2). This results demonstrate the impact in the post-pandemic era of H1N1pdm virus, with increased risk of severe disease, in relation to H3N2 virus, both viruses co-circulating during 2013. © 2017 Wiley Periodicals, Inc.

  20. Pandemic Paradox: Early Life H2N2 Pandemic Influenza Infection Enhanced Susceptibility to Death during the 2009 H1N1 Pandemic.

    PubMed

    Gagnon, Alain; Acosta, Enrique; Hallman, Stacey; Bourbeau, Robert; Dillon, Lisa Y; Ouellette, Nadine; Earn, David J D; Herring, D Ann; Inwood, Kris; Madrenas, Joaquin; Miller, Matthew S

    2018-01-16

    Recent outbreaks of H5, H7, and H9 influenza A viruses in humans have served as a vivid reminder of the potentially devastating effects that a novel pandemic could exert on the modern world. Those who have survived infections with influenza viruses in the past have been protected from subsequent antigenically similar pandemics through adaptive immunity. For example, during the 2009 H1N1 "swine flu" pandemic, those exposed to H1N1 viruses that circulated between 1918 and the 1940s were at a decreased risk for mortality as a result of their previous immunity. It is also generally thought that past exposures to antigenically dissimilar strains of influenza virus may also be beneficial due to cross-reactive cellular immunity. However, cohorts born during prior heterosubtypic pandemics have previously experienced elevated risk of death relative to surrounding cohorts of the same population. Indeed, individuals born during the 1890 H3Nx pandemic experienced the highest levels of excess mortality during the 1918 "Spanish flu." Applying Serfling models to monthly mortality and influenza circulation data between October 1997 and July 2014 in the United States and Mexico, we show corresponding peaks in excess mortality during the 2009 H1N1 "swine flu" pandemic and during the resurgent 2013-2014 H1N1 outbreak for those born at the time of the 1957 H2N2 "Asian flu" pandemic. We suggest that the phenomenon observed in 1918 is not unique and points to exposure to pandemic influenza early in life as a risk factor for mortality during subsequent heterosubtypic pandemics. IMPORTANCE The relatively low mortality experienced by older individuals during the 2009 H1N1 influenza virus pandemic has been well documented. However, reported situations in which previous influenza virus exposures have enhanced susceptibility are rare and poorly understood. One such instance occurred in 1918-when those born during the heterosubtypic 1890 H3Nx influenza virus pandemic experienced the highest