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  1. 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 ...

  2. Pandemic H1N1 influenza virus in Chilean commercial turkeys with genetic and serologic comparisons to U.S. H1N1 avian influenza vaccine isolates.

    PubMed

    Kapczynski, Darrell R; Gonder, Eric; Tilley, Becky; Hernandez, Andres; Hodgson, Jorge; Wojcinski, Helen; Jiang, Haijun; Suarez, David L

    2011-12-01

    Beginning in April 2009, a novel H1N1 influenza virus caused acute respiratory disease in humans, first in Mexico and then around the world. The resulting pandemic influenza A H1N1 2009 (pH1N1) virus was isolated in swine in Canada in June 2009 and later in breeder turkeys in Chile, Canada, and the United States. The pH1N1 virus consists of gene segments of avian, human, and swine influenza origin and has the potential for infection in poultry following exposure to infected humans or swine. We examined the clinical events following the initial outbreak of pH1N1 in turkeys and determined the relatedness of the hemagglutinin (HA) gene segments from the pH1N1 to two H1N1 avian influenza (AI) isolates used in commercial turkey inactivated vaccines. Overall, infection of turkey breeder hens with pH1N1 resulted in -50% reduction of egg production over 3-4 weeks. Genetic analysis indicated one H1N1 AI vaccine isolate (Alturkey/North Carolina/17026/1988) contained approximately 92% nucleotide sequence similarity to the pH1N1 virus (A/Mexico/4109/2009); whereas, a more recent AI vaccine isolate (A/ swine/North Carolina/00573/2005) contained 75.9% similarity. Comparison of amino acids found at antigenic sites of the HA protein indicated conserved epitopes at the Sa site; however, major differences were found at the Ca2 site between pH1N1 and A/ turkey/North Carolina/127026/1988. Hemagglutinin-inhibition (HI) tests were conducted with sera produced in vaccinated turkeys in North Carolina to determine if protection would be conferred using U.S. AI vaccine isolates. HI results indicate positive reactivity (HI titer > or = 5 log2) against the vaccine viruses over the course of study. However, limited cross-reactivity to the 2009 pH1N1 virus was observed, with positive titers in a limited number of birds (6 out of 20) beginning only after a third vaccination. Taken together, these results demonstrate that turkeys treated with these vaccines would likely not be protected against pH

  3. Perspectives of Pulmonologists on the 2009-2010 H1N1 Vaccination Effort.

    PubMed

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

    2012-01-01

    Persons with high-risk conditions such as asthma were a target group for H1N1 vaccine recommendations. We conducted a mailed survey of a national sample of pulmonologists to understand their participation in the 2009-2010 H1N1 vaccine campaign. The response rate was 59%. The majority of pulmonologists strongly recommended H1N1 vaccine for children (73%) and adults aged 25-64 years (51%). Only 60% of respondents administered H1N1 vaccine in their practice compared to 87% who offered seasonal influenza vaccine. Other than vaccine supply, respondents who provided H1N1 vaccine reported few logistical problems. Two-thirds of respondents would be very likely to vaccinate during a future influenza pandemic; this rate was higher among those who provided H1N1 vaccine and/or seasonal flu vaccine. In total, the H1N1 vaccine-related experiences of pulmonologists seemed to be positive. However, additional efforts are needed to increase participation in future pandemic vaccination campaigns.

  4. Influenza vaccination coverage among pregnant women--National 2009 H1N1 Flu Survey (NHFS).

    PubMed

    Ding, Helen; Santibanez, Tammy A; Jamieson, Denise J; Weinbaum, Cindy M; Euler, Gary L; Grohskopf, Lisa A; Lu, Peng-Jun; Singleton, James A

    2011-06-01

    We sought to describe vaccination with influenza A (H1N1) 2009 monovalent (2009 H1N1) and trivalent seasonal (seasonal) vaccines among pregnant women during the 2009 through 2010 influenza season. A national H1N1 flu survey was conducted April through June 2010. The 2009 H1N1 and seasonal vaccination coverage estimates were 45.7% and 32.1%, respectively, among pregnant women aged 18-49 years. Receipt of a health care provider's recommendation for vaccination, perceived effectiveness of influenza vaccinations, and perceived high chance of influenza infection were independently associated with higher 2009 H1N1 and seasonal vaccination coverage. Pregnancy during October 2009 through January 2010 was independently associated with higher 2009 H1N1 vaccination coverage. The 2009 H1N1 vaccination level among pregnant women was higher than the seasonal vaccination level during the 2009 through 2010 season; it was also higher than vaccination among nonpregnant women with and without high-risk conditions. Health care providers and public health messaging played important roles in influencing vaccination behavior.

  5. Predicting H1N1 vaccine uptake and H1N1-related health beliefs: the role of individual difference in consideration of future consequences.

    PubMed

    Nan, Xiaoli; Kim, Jarim

    2014-01-01

    This research examines the influence of individual difference in consideration of future consequences on H1N1 vaccine uptake and H1N1-related health beliefs (i.e., perceived susceptibility to and severity of the H1N1 flu, perceived efficacy and safety of the H1N1 vaccine, and perceived self-efficacy in obtaining the H1N1 vaccine). A survey of 411 college students showed that consideration of future consequences had no direct effect on vaccine uptake, but higher consideration of future consequences was associated with greater perceived severity of the flu, higher perceived effectiveness of the vaccine, and greater perceived self-efficacy. Additional analysis suggested that consideration of future consequences had a significant indirect effect on vaccine uptake through perceived vaccine efficacy. Results of the study also revealed gender and racial differences in some of the H1N1-related health beliefs. Implications of the findings for vaccine risk communication are discussed.

  6. Vitamin D Levels, Natural H1N1 Infection and Response to H1N1 Vaccine among HIV-Infected Individuals.

    PubMed

    Momplaisir, Florence; Frank, Ian; Meyer, Wa; Kim, Deborah; Kappes, Rosemary; Tebas, Pablo

    2012-05-20

    BACKGROUND: Beyond its role in calcium homeostasis, vitamin D plays a critical role in immunological responses to pathogens. We evaluated the relationship between 25-OH vitamin D levels and susceptibility to natural H1N1 infection and H1N1 vaccine responses in HIV infected individuals. METHODS: This was a sub study of an H1N1 vaccine trial conducted at the University of Pennsylvania in 2009/10. We compared the 25-OH vitamin D levels among individuals with and without baseline evidence of prior H1N1 infection and between vaccine responders and non-responders. RESULTS: 120 participants enrolled in the trial, 71% male, 68% African American, median age 46 years. The majority had controlled HIV disease. At baseline, 86% had 25-OH vitamin D levels < 30 ng/ml and 54% had levels < 20 ng/ml. Thirty participants (25%) had evidence of prior H1N1 exposure. There was no difference in mean 25-OH vitamin D levels among patients with or without prior natural H1N1 infection (21 ng/ml vs 20 ng/ml, p=0.72). Among participants without previous H1N1 exposure, only 61% developed protective antibody titers following vaccination. 25-OH vitamin D levels were similar between vaccine responders (20 ng/ml) and non-responders (20 ng/ml) (p=0.83). CONCLUSION: Although 25-OH vitamin D deficiency was very common among HIV-infected individuals, it was not associated with natural susceptibility to H1N1 or to vaccine responses.

  7. College students' perceptions of H1N1 flu risk and attitudes toward vaccination.

    PubMed

    Ramsey, Meagan A; Marczinski, Cecile A

    2011-10-13

    College students are highly susceptible to the H1N1 virus, yet previous studies suggest that college students perceive themselves at low risk for the flu. We surveyed 514 undergraduates to assess their perceptions of H1N1 flu risk and opinions about flu vaccines. A third of respondents stated that they were not at risk of getting the H1N1 flu because they were young. Responses indicated a distrust of the safety and effectiveness of influenza vaccinations; only 15.8% of participants planned on receiving H1N1 vaccination. Top reasons for refusing the H1N1 vaccine included questioning vaccine safety and effectiveness, and concerns about potential serious and/or benign side effects. Top reasons for H1N1 vaccination acceptance included receiving a doctor recommendation for the vaccine, having previously gotten a seasonal vaccine, and being at high-risk for influenza. Our findings suggest that college students are inaccurate in assessing their risk level and are unlikely to seek vaccinations.

  8. Vaccine Narratives and Public Health: Investigating Criticisms of H1N1 Pandemic Vaccination.

    PubMed

    Abeysinghe, Sudeepa

    2015-02-25

    Vaccine hesitancy is often understood and explored on the level of individual decision-making. However, questions surrounding the risk and efficacy of vaccination are evident in wider public discourse; social narratives of vaccination inform and impact on the individual level. This paper takes a narrative analysis approach from the sociology of health to examine data drawn from a wider study on global public health responses to the H1N1 pandemic. The paper concentrates upon criticisms to mass vaccination as recounted within the Council of Europe's debate of the handling of H1N1. It shows that three narratives were particularly dominant: problematizing the use of vaccination as a public health response; criticising the efficacy of the vaccines; and, questioning the safety of the strategy. This debate presents an important case study in understanding the way in which vaccines are problematized within the public discourse.

  9. 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.

  10. Vaccine-related internet search activity predicts H1N1 and HPV vaccine coverage: implications for vaccine acceptance.

    PubMed

    Kalichman, Seth C; Kegler, Christopher

    2015-01-01

    The Internet is a primary source for health-related information, and Internet search activity is associated with infectious disease outbreaks. The authors hypothesized that Internet search activity for vaccine-related information would predict vaccination coverage. They examined Internet search activity for H1N1 and human papilloma virus (HPV) disease and vaccine information in relation to H1N1 and HPV vaccine uptake. Google Insight for Search was used to assess the volume of Internet search queries for H1N1- and vaccine-related terms in the United States in 2009, the year of the H1N1 pandemic. Vaccine coverage data were also obtained from the Centers for Disease Control and Prevention at the state level for H1N1 vaccinations in 2009. These same measures were collected at the state level for HPV- and vaccine-related search terms in 2010 as well as HPV vaccine uptake in that year. Analyses showed that the search terms H1N1 and vaccine were correlated with H1N1 vaccine uptake; ordinal regression found the H1N1 search term was independently associated with H1N1 vaccine coverage. Similarly, the correlation between vaccine search volume and HPV coverage was significant; ordinal regression showed the search term vaccine independently predicted HPV vaccination coverage. This is among the first studies to show that Internet search activity is associated with vaccination coverage. The Internet should be exploited as an opportunity to dispel vaccine misinformation by providing accurate information to support vaccine decision making.

  11. Learning from Successful School-based Vaccination Clinics during 2009 pH1N1

    ERIC Educational Resources Information Center

    Klaiman, Tamar; O'Connell, Katherine; Stoto, Michael A.

    2014-01-01

    Background: The 2009 H1N1 vaccination campaign was the largest in US history. State health departments received vaccines from the federal government and sent them to local health departments (LHDs) who were responsible for getting vaccines to the public. Many LHD's used school-based clinics to ensure children were the first to receive limited…

  12. Cases of Narcolepsy-Cataplexy Syndrome Following H1N1 Vaccination

    PubMed Central

    NALBANTOĞLU, Mecbure; BENBİR, Gülçin; KARADENİZ, Derya; ALTINTAŞ, Ayşe; SAVRAN OĞUZ, Fatma

    2014-01-01

    Narcolepsy-Cataplexy syndrome is a rare sleep disorder related with human leukocyte antigens (HLA-DQB1*0602) caused by the loss of hypothalamic hypocretin/orexin producing neurons. Recently, in European countries, Narcolepsy-Cataplexy syndrome developing following H1N1 vaccination has attracted attention. Our first patient was a 9-year-old boy, who was referred to our clinic with the complaint of daytime sleepiness developed 1.5 month after H1N1 vaccination. After a couple of weeks, weakness of the upper extremities while laughing was added to the clinical picture. He also developed hypnopompic hallucinations and nightmares. Multiple sleep latency test (MSLT) following full-night polysomnography (PSG) showed that the mean sleep latency was 0.6 minutes; and all of the naps had sleep-onset REM periods. Our second patient was a 50 year-oldman, who presented to our clinic complaining of sleep paralysis and REM sleep behavior disorder developed 4 months after H1N1 vaccination. He developed daytime sleepiness 6 months after and cataplexy 8 months after H1N1 vaccination. He was also diagnosed as having Narcolepsy-Cataplexy syndrome upon PSG and MSLT. We investigated HLA-DRB1/ DQB1 locus with Polymerase Chain Reaction-Sequence Specific Primer technique. The first patient had HLA-DQB1*0602.47 and DQB1*03.01 heterozygous loci; and the second patient had HLA-DQB1*0602.47 and DQB1*02.01 heterozygous loci. These patients are the first reported cases of Narcolepsy-Cataplexy syndrome related with H1N1 vaccination in Turkey. Although there is no specific marker, temporal relationship between vaccination and onset of disease symptoms suggests a possible causal relationship. In the presence of an underlying genetic predisposition, it was thought that H1N1 vaccination could trigger Narcolepsy-Cataplexy syndrome.

  13. 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…

  14. 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…

  15. Novel pandemic A (H1N1) influenza vaccination among pregnant women: motivators and barriers.

    PubMed

    Steelfisher, Gillian K; Blendon, Robert J; Bekheit, Mark M; Mitchell, Elizabeth W; Williams, Jennifer; Lubell, Keri; Peugh, Jordon; DiSogra, Charles A

    2011-06-01

    We sought to examine motivators and barriers related to monovalent 2009 influenza A (H1N1) vaccination among pregnant women. We conducted a national poll of pregnant women using a random online sample (237) and opt-in supplement (277). In all, 42% of pregnant women reported getting the vaccine. Vaccination was positively associated with attitudinal factors including believing the vaccine is very safe or benefits the baby, and with provider recommendations. Women in racial/ethnic minority groups, women with less education, and women <35 years were less likely to get the vaccine and had differing views and experiences. Despite H1N1 vaccination rates that are higher than past seasonal influenza rates, barriers like safety concerns may persist in a pandemic. Messaging from providers that encourages women to believe the vaccine is very safe and benefits their baby may be compelling. Messaging and outreach during future pandemics may require customization to increase vaccination among high-risk groups.

  16. Neuronal Antibodies in Children with or without Narcolepsy following H1N1-AS03 Vaccination.

    PubMed

    Thebault, Simon; Waters, Patrick; Snape, Matthew D; Cottrell, Dominic; Darin, Niklas; Hallböök, Tove; Huutoniemi, Anne; Partinen, Markku; Pollard, Andrew J; Vincent, Angela

    2015-01-01

    Type 1 narcolepsy is caused by deficiency of hypothalamic orexin/hypocretin. An autoimmune basis is suspected, but no specific antibodies, either causative or as biomarkers, have been identified. However, the AS03 adjuvanted split virion H1N1 (H1N1-AS03) vaccine, created to protect against the 2009 Pandemic, has been implicated as a trigger of narcolepsy particularly in children. Sera and CSFs from 13 H1N1-AS03-vaccinated patients (12 children, 1 young adult) with type 1 narcolepsy were tested for autoantibodies to known neuronal antigens including the N-methyl-D-aspartate receptor (NMDAR) and contactin-associated protein 2 (CASPR2), both associated with encephalopathies that include disordered sleep, to rodent brain tissue including the lateral hypothalamus, and to live hippocampal neurons in culture. When sufficient sample was available, CSF levels of melanin-concentrating hormone (MCH) were measured. Sera from 44 H1N1-ASO3-vaccinated children without narcolepsy were also examined. None of these patients' CSFs or sera was positive for NMDAR or CASPR2 antibodies or binding to neurons; 4/13 sera bound to orexin-neurons in rat brain tissue, but also to other neurons. MCH levels were a marginally raised (n = 8; p = 0.054) in orexin-deficient narcolepsy patients compared with orexin-normal children (n = 6). In the 44 H1N1-AS03-vaccinated healthy children, there was no rise in total IgG levels or in CASPR2 or NMDAR antibodies three weeks following vaccination. In conclusion, there were no narcolepsy-specific autoantibodies identified in type 1 narcolepsy sera or CSFs, and no evidence for a general increase in immune reactivity following H1N1-AS03 vaccination in the healthy children. Antibodies to other neuronal specific membrane targets, with their potential for directing use of immunotherapies, are still an important goal for future research.

  17. Attitudes toward and Uptake of H1N1 Vaccine among Health Care Workers during the 2009 H1N1 Pandemic

    PubMed Central

    Henriksen Hellyer, Joan M.; DeVries, Aaron S.; Jenkins, Sarah M.; Lackore, Kandace A.; James, Katherine M.; Ziegenfuss, Jeanette Y.; Poland, Gregory A.; Tilburt, Jon C.

    2011-01-01

    Background Though recommended by many and mandated by some, influenza vaccination rates among health care workers, even in pandemics, remain below optimal levels. The objective of this study was to assess vaccination uptake, attitudes, and distinguishing characteristics (including doctor-nurse differences) of health care workers who did and did not receive the pandemic H1N1 influenza vaccine in late 2009. Methodology/Principal Findings In early 2010 we mailed a self-administered survey to 800 physicians and 800 nurses currently licensed and practicing in Minnesota. 1,073 individuals responded (cooperation rate: 69%). 85% and 62% of Minnesota physicians and nurses, respectively, reported being vaccinated. Accurately estimating the risk of vaccine side effects (OR 2.0; 95% CI 1.5–2.7), agreeing with a professional obligation to be vaccinated (OR 10.1; 95% CI 7.1–14.2), an ethical obligation to follow public health authorities' recommendations (OR 9.9; 95% CI 6.6–14.9), and laws mandating pandemic vaccination (OR 3.1; 95% CI 2.3–4.1) were all independently associated with receiving the H1N1 influenza vaccine. Conclusions/Significance While a majority of health care workers in one midwestern state reported receiving the pandemic H1N1 vaccine, physicians and nurses differed significantly in vaccination uptake. Several key attitudes and perceptions may influence health care workers' decisions regarding vaccination. These data inform how states might optimally enlist health care workers' support in achieving vaccination goals during a pandemic. PMID:22216290

  18. Pandemic 2009 H1N1 vaccine protects against 1918 Spanish influenza virus.

    PubMed

    Medina, Rafael A; Manicassamy, Balaji; Stertz, Silke; Seibert, Christopher W; Hai, Rong; Belshe, Robert B; Frey, Sharon E; Basler, Christopher F; Palese, Peter; García-Sastre, Adolfo

    2010-06-15

    The 1918 influenza A virus caused the most devastating pandemic, killing approximately 50 million people worldwide. Immunization with 1918-like and classical swine H1N1 virus vaccines results in cross-protective antibodies against the 2009 H1N1 pandemic influenza, indicating antigenic similarities among these viruses. In this study, we demonstrate that vaccination with the 2009 pandemic H1N1 vaccine elicits 1918 virus cross-protective antibodies in mice and humans, and that vaccination or passive transfer of human-positive sera reduced morbidity and conferred full protection from lethal challenge with the 1918 virus in mice. The spread of the 2009 H1N1 influenza virus in the population worldwide, in addition to the large number of individuals already vaccinated, suggests that a large proportion of the population now have cross-protective antibodies against the 1918 virus, greatly alleviating concerns and fears regarding the accidental exposure/release of the 1918 virus from the laboratory and the use of the virus as a bioterrorist agent.

  19. Narcolepsy and A(H1N1)pdm09 vaccination

    PubMed Central

    van der Most, Robbert; Van Mechelen, Marcelle; Destexhe, Eric; Wettendorff, Martine; Hanon, Emmanuel

    2014-01-01

    Epidemiological data from several European countries suggested an increased risk of the chronic sleep disorder narcolepsy following vaccination with Pandemrix™, an AS03-adjuvanted, pandemic A(H1N1)pdm09 influenza vaccine. Further research to investigate potential associations between Pandemrix™ vaccination, A(H1N1)pdm09 influenza infection and narcolepsy is required. Narcolepsy is most commonly caused by a reduction or absence of hypocretin produced by hypocretin-secreting neurons in the hypothalamus, and is tightly associated with HLA-II DQB1*06:02. Consequently, research focusing on CD4+ T-cell responses, building on the hypothesis that for disease development, T cells specific for antigen(s) from hypocretin neurons must be activated or reactivated, is considered essential. Therefore, the following key areas of research can be identified, (1) characterization of hypothetical narcolepsy-specific auto-immune CD4+ T cells, (2) mapping epitopes of such T cells, and (3) evaluating potential mechanisms that would enable such cells to gain access to the hypothalamus. Addressing these questions could further our understanding of the potential links between narcolepsy and A(H1N1)pdm09 vaccination and/or infection. Of particular interest is that any evidence of a mimicry-based mechanism could also explain the association between narcolepsy and A(H1N1)pdm09 influenza infection. PMID:24342916

  20. Determinants of Parental Acceptance of the H1N1 Vaccine.

    PubMed

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

    2014-06-01

    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 of the H1N1 vaccine, we examined data from a representative national sample of parents (n = 684), using the health belief model as a framework. The most important predictors of vaccine acceptance were "cues to action" at multiple levels, from intrapersonal to mass communication, including the influence of friends, family, the media, and modeling by the Obama family; costs and benefits and self-efficacy were also significant predictors of vaccine acceptance. Higher perceived levels of H1N1 risk were not associated with vaccine uptake. Results suggest that traditional measures of perceived risk may not account for the cost-benefit analysis inherent in vaccine decision making, and that messages designed to emphasize disease risk may be ineffective. The authors recommend emphasizing cues to action that support norming and modeling of vaccine acceptance.

  1. Racial and ethnic disparities in uptake and location of vaccination for 2009-H1N1 and seasonal influenza.

    PubMed

    Uscher-Pines, Lori; Maurer, Jurgen; Harris, Katherine M

    2011-07-01

    To learn more about racial and ethnic disparities in influenza vaccination during the 2009-H1N1 pandemic, we examined nationally representative survey data of US adults. We found disparities in 2009-H1N1 vaccine uptake between Blacks and Whites (13.8% vs 20.4%); Whites and Hispanics had similar 2009-H1N1 vaccination rates. Physician offices were the dominant location for 2009-H1N1 and seasonal influenza vaccinations, especially among minorities. Our results highlight the need for a better understanding of how communication methods and vaccine distribution strategies affect vaccine uptake within minority communities.

  2. Narcolepsy as an autoimmune disease: the role of H1N1 infection and vaccination.

    PubMed

    Partinen, Markku; Kornum, Birgitte Rahbek; Plazzi, Giuseppe; Jennum, Poul; Julkunen, Ilkka; Vaarala, Outi

    2014-06-01

    Narcolepsy is a sleep disorder characterised by loss of hypothalamic hypocretin (orexin) neurons. The prevalence of narcolepsy is about 30 per 100 000 people, and typical age at onset is 12-16 years. Narcolepsy is strongly associated with the HLA-DQB1*06:02 genotype, and has been thought of as an immune-mediated disease. Other risk genes, such as T-cell-receptor α chain and purinergic receptor subtype 2Y11, are also implicated. Interest in narcolepsy has increased since the epidemiological observations that H1N1 infection and vaccination are potential triggering factors, and an increase in the incidence of narcolepsy after the pandemic AS03 adjuvanted H1N1 vaccination in 2010 from Sweden and Finland supports the immune-mediated pathogenesis. Epidemiological observations from studies in China also suggest a role for H1N1 virus infections as a trigger for narcolepsy. Although the pathological mechanisms are unknown, an H1N1 virus-derived antigen might be the trigger.

  3. Associations between health communication behaviors, neighborhood social capital, vaccine knowledge, and parents' H1N1 vaccination of their children.

    PubMed

    Jung, Minsoo; Lin, Leesa; Viswanath, K

    2013-10-01

    During the H1N1 pandemic in 2009-10, the vaccination behavior of parents played a critical role in preventing and containing the spread of the disease and the subsequent health outcomes among children. Several studies have examined the relationship between parents' health communication behaviors and vaccinations for children in general. Little is known, however, about the link between parents' health communication behaviors and the vaccination of their children against the H1N1 virus, and their level of vaccine-related knowledge. We drew on a national survey among parents with at least one child less than 18 years of age (n=639) to investigate Parents' H1N1-related health communication behaviors including sources of information, media exposure, information-seeking behaviors, H1N1-related knowledge, and neighborhood social capital, as well as the H1N1 vaccination rates of their children. Findings showed that there is a significant association between the degree at which parents obtained H1N1 vaccination for their children and health communication variables: watching the national television news and actively seeking H1N1 information. And this association was moderated by the extent of the parents' H1N1-related knowledge. In addition, the parents' degree of neighborhood social capital mediated the association between H1N1 knowledge of the parents and H1N1 vaccination acceptance for their children. We found, compared to those with a low-level of neighborhood social capital, parents who have a high-level of neighborhood social capital are more likely to vaccinate their children. These findings suggest that it is necessary to design a strategic health communication campaign segmented by parent health communication behaviors.

  4. Immunogenicity of Virus Like Particle Forming Baculoviral DNA Vaccine against Pandemic Influenza H1N1

    PubMed Central

    Gwon, Yong-Dae; Kim, Sehyun; Cho, Yeondong; Heo, Yoonki; Cho, Hansam; Park, Kihoon; Lee, Hee-Jung; Choi, Jiwon; Poo, Haryoung; Kim, Young Bong

    2016-01-01

    An outbreak of influenza H1N1 in 2009, representing the first influenza pandemic of the 21st century, was transmitted to over a million individuals and claimed 18,449 lives. The current status in many countries is to prepare influenza vaccine using cell-based or egg-based killed vaccine. However, traditional influenza vaccine platforms have several limitations. To overcome these limitations, many researchers have tried various approaches to develop alternative production platforms. One of the alternative approach, we reported the efficacy of influenza HA vaccination using a baculoviral DNA vaccine (AcHERV-HA). However, the immune response elicited by the AcHERV-HA vaccine, which only targets the HA antigen, was lower than that of the commercial killed vaccine. To overcome the limitations of this previous vaccine, we constructed a human endogenous retrovirus (HERV) envelope-coated, baculovirus-based, virus-like-particle (VLP)–forming DNA vaccine (termed AcHERV-VLP) against pandemic influenza A/California/04/2009 (pH1N1). BALB/c mice immunized with AcHERV-VLP (1×107 FFU AcHERV-VLP, i.m.) and compared with mice immunized with the killed vaccine or mice immunized with AcHERV-HA. As a result, AcHERV-VLP immunization produced a greater humoral immune response and exhibited neutralizing activity with an intrasubgroup H1 strain (PR8), elicited neutralizing antibody production, a high level of interferon-γ secretion in splenocytes, and diminished virus shedding in the lung after challenge with a lethal dose of influenza virus. In conclusion, VLP-forming baculovirus DNA vaccine could be a potential vaccine candidate capable of efficiently delivering DNA to the vaccinee and VLP forming DNA eliciting stronger immunogenicity than egg-based killed vaccines. PMID:27149064

  5. An Influenza A/H1N1/2009 Hemagglutinin Vaccine Produced in Escherichia coli

    PubMed Central

    Aguilar-Yáñez, José M.; Portillo-Lara, Roberto; Mendoza-Ochoa, Gonzalo I.; García-Echauri, Sergio A.; López-Pacheco, Felipe; Bulnes-Abundis, David; Salgado-Gallegos, Johari; Lara-Mayorga, Itzel M.; Webb-Vargas, Yenny; León-Angel, Felipe O.; Rivero-Aranda, Ramón E.; Oropeza-Almazán, Yuriana; Ruiz-Palacios, Guillermo M.; Zertuche-Guerra, Manuel I.; DuBois, Rebecca M.; White, Stephen W.; Schultz-Cherry, Stacey; Russell, Charles J.; Alvarez, Mario M.

    2010-01-01

    Background The A/H1N1/2009 influenza pandemic made evident the need for faster and higher-yield methods for the production of influenza vaccines. Platforms based on virus culture in mammalian or insect cells are currently under investigation. Alternatively, expression of fragments of the hemagglutinin (HA) protein in prokaryotic systems can potentially be the most efficacious strategy for the manufacture of large quantities of influenza vaccine in a short period of time. Despite experimental evidence on the immunogenic potential of HA protein constructs expressed in bacteria, it is still generally accepted that glycosylation should be a requirement for vaccine efficacy. Methodology/Principal Findings We expressed the globular HA receptor binding domain, referred to here as HA63–286-RBD, of the influenza A/H1N1/2009 virus in Escherichia coli using a simple, robust and scalable process. The recombinant protein was refolded and purified from the insoluble fraction of the cellular lysate as a single species. Recombinant HA63–286-RBD appears to be properly folded, as shown by analytical ultracentrifugation and bio-recognition assays. It binds specifically to serum antibodies from influenza A/H1N1/2009 patients and was found to be immunogenic, to be capable of triggering the production of neutralizing antibodies, and to have protective activity in the ferret model. Conclusions/Significance Projections based on our production/purification data indicate that this strategy could yield up to half a billion doses of vaccine per month in a medium-scale pharmaceutical production facility equipped for bacterial culture. Also, our findings demonstrate that glycosylation is not a mandatory requirement for influenza vaccine efficacy. PMID:20661476

  6. Pandemic H1N1 influenza virus in Chilean commercial turkeys with genetic and serologic comparisons to U.S. H1N1 avian influenza vaccine isolates

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Beginning in April 2009, a novel H1N1 influenza virus has caused acute respiratory disease in humans, first in Mexico and then spreading around the world. The resulting pandemic influenza A H1N1 2009 (pH1N1) virus was isolated in swine in Canada in June, 2009, and later in turkey breeders in Chile, ...

  7. 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…

  8. Safety of the Pandemic H1N1 Influenza Vaccine among Pregnant U.S. Military Women and Their Newborns

    DTIC Science & Technology

    2013-03-01

    Naval Health Research Center Safety of the Pandemic H1N1 Influenza Vaccine among Pregnant Women and Their Newborns Ava M.S. Conlin Anna...Safety of the Pandemic H1N1 Influenza Vaccine Among Pregnant U.S. Military Women and Their Newborns Ava Marie S. Conlin, DO, MPH, Anna T. Bukowinski...active-duty U.S. military women who received pandemic H1N1 vaccine during pregnancy as well as adverse health outcomes among the newborns resulting from

  9. 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

  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. Predicting peptide vaccine candidates against H1N1 influenza virus through theoretical approaches.

    PubMed

    Bello, Martiniano; Campos-Rodriguez, Rafael; Rojas-Hernandez, Saul; Contis-Montes de Oca, Arturo; Correa-Basurto, José

    2015-05-01

    Identification of potential epitopes that might activate the immune system has been facilitated by the employment of algorithms that use experimental data as templates. However, in order to prove the affinity and the map of interactions between the receptor (major histocompatibility complex, MHC, or T-cell receptor) and the potential epitope, further computational studies are required. Docking and molecular dynamics (MDs) simulations have been an effective source of generating structural information at molecular level in immunology. Herein, in order to provide a detailed understanding of the origins of epitope recognition and to select the best peptide candidate to develop an epitope-based vaccine, docking and MDs simulations in combination with MMGBSA free energy calculations and per-residue free energy decomposition were performed, taking as starting complexes those formed between four designed epitopes (P1-P4) from hemagglutinin (HA) of the H1N1 influenza virus and MHC-II anchored in POPC membrane. Our results revealed that the energetic contributions of individual amino acids within the pMHC-II complexes are mainly dictated by van der Waals interactions and the nonpolar part of solvation energy, whereas the electrostatic interactions corresponding to hydrogen bonds and salt bridges determine the binding specificity, being the most favorable interactions formed between p4 and MHC-II. Then, P1-P4 epitopes were synthesized and tested experimentally to compare theoretical and experimental results. Experimental results show that P4 elicited the highest strong humoral immune response to HA of the H1N1 and may induce antibodies that are cross-reactive to other influenza subtypes, suggesting that it could be a good candidate for the development of a peptide-based vaccine.

  12. The Decision to Vaccinate or Not during the H1N1 Pandemic: Selecting the Lesser of Two Evils?

    PubMed Central

    Ashbaugh, Andrea R.; Herbert, Christophe F.; Saimon, Elena; Azoulay, Nelson; Olivera-Figueroa, Lening; Brunet, Alain

    2013-01-01

    Background With the release of the H1N1 vaccine, there was much controversy surrounding its use despite strong encouragements to be vaccinated in the media. Though studies have examined factors influencing people's decision to be vaccinated, few have focused on how general beliefs about the world or where an individual gathers information might influence that decision. Methodology/Principal Findings A cross-sectional web-based survey (N = 817) was conducted during the H1N1 outbreak after the vaccine was available. Variables examined included sociodemographic information, health related behaviours, specific beliefs concerning the H1N1 virus and its vaccine, as well as general beliefs, such as fear of contamination, intolerance of uncertainty, emotional states, coping behaviour, and the source of information concerning the virus. Three converging statistical methods were used to examine the associations – analysis of variance, logistic regression, and recursive partition modelling. The most consistent and strongest association was that negative beliefs about the H1N1 vaccine (e.g. fear of its side effects) was related to the decision not to be vaccinated, whereas beliefs about the dangers of the H1N1 virus was related to the decision to be vaccinated. Most notably, having very strong negative beliefs about the vaccine was a more powerful predictor than even strong beliefs about the dangers of the H1N1 virus. Furthermore, obtaining information from the Internet, as compared to more traditional sources of information (e.g., TV, newspapers) was related to the decision not to be vaccinated. Conclusions/Significance These results are consistent with the Health Belief Model. Importantly they suggest that during future pandemics public health officials should not only discuss the dangers of the pandemic but also (i) take additional steps to reassure the public about the safety of vaccines and (ii) monitor the information disseminated over the Internet rather than

  13. Improving influenza vaccine distribution in preparation for an H1N1 influenza pandemic: lessons from the field.

    PubMed

    Wahlen, Mongeon Kari J; Bessette, Richard R; Bernard, Matthew E; Springer, Donna J; Benson, Catherine A

    2010-01-01

    Vaccine distribution is an essential component of any healthcare organization's pandemic influenza plan. Variables surrounding distribution in these circumstances are often difficult to anticipate and require careful consideration. The 2009 H1N1 influenza pandemic provided organizations with an opportunity to test current models and overall organizational readiness for the next influenza pandemic. This article describes the experiences at a large, midwestern, multispecialty medical system in responding to the unique circumstances surrounding distribution of the 2009 H1N1 influenza vaccine. We discuss challenges, variables to consider when choosing a vaccine distribution model, institutional response, and lessons learned.

  14. Virus-Like Particle Vaccine Containing Hemagglutinin Confers Protection against 2009 H1N1 Pandemic Influenza ▿

    PubMed Central

    Hossain, M. Jaber; Bourgeois, Melissa; Quan, Fu-Shi; Lipatov, Aleksandr S.; Song, Jae-Min; Chen, Li-Mei; Compans, Richard W.; York, Ian; Kang, Sang-Moo; Donis, Ruben O.

    2011-01-01

    Immunization of the world population before an influenza pandemic such as the 2009 H1N1 virus spreads globally is not possible with current vaccine production platforms. New influenza vaccine technologies, such as virus-like-particles (VLPs), offer a promising alternative. Here, we tested the immunogenicity and protective efficacy of a VLP vaccine containing hemagglutinin (HA) and M1 from the 2009 pandemic H1N1 influenza virus (H1N1pdm) in ferrets and compared intramuscular (i.m.) and intranasal (i.n.) routes of immunization. Vaccination of ferrets with VLPs containing the M1 and HA proteins from A/California/04/2009 (H1N1pdm) induced high antibody titers and conferred significant protection against virus challenge. VLP-vaccinated animals lost less weight, shed less virus in nasal washes, and had markedly lower virus titers in all organs tested than naïve controls. A single dose of VLPs, either i.m. or i.n., induced higher levels of antibody than did two doses of commercial split vaccine. Ferrets vaccinated with split vaccine were incompletely protected against challenge; these animals had lower virus titers in olfactory bulbs, tonsils, and intestines, but lost weight and shed virus in nasal washes to a similar extent as naïve controls. Challenge with heterologous A/Brisbane/59/07 (H1N1) virus revealed that the VLPs conferred minimal cross-protection to heterologous infection, as revealed by the lack of reduction in nasal wash and lung virus titers and slightly higher weight loss relative to controls. In summary, these experiments demonstrate the strong immunogenicity and protective efficacy of VLPs compared to the split vaccine and show that i.n. vaccination with VLPs has the potential for highly efficacious vaccination against influenza. PMID:22030367

  15. 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

  16. A/H1N1 Vaccine Intentions in College Students: An Application of the Theory of Planned Behavior

    ERIC Educational Resources Information Center

    Agarwal, Vinita

    2014-01-01

    Objective: To test the applicability of the Theory of Planned Behavior (TPB) in college students who have not previously received the A/H1N1 vaccine. Participants: Undergraduate communication students at a metropolitan southern university. Methods: In January-March 2010, students from voluntarily participating communication classes completed a…

  17. Narcolepsy and A(H1N1)pdm09 vaccination: shaping the research on the observed signal.

    PubMed

    van der Most, Robbert; Van Mechelen, Marcelle; Destexhe, Eric; Wettendorff, Martine; Hanon, Emmanuel

    2014-01-01

    Epidemiological data from several European countries suggested an increased risk of the chronic sleep disorder narcolepsy following vaccination with Pandemrix(™), an AS03-adjuvanted, pandemic A(H1N1)pdm09 influenza vaccine. Further research to investigate potential associations between Pandemrix™ vaccination, A(H1N1)pdm09 influenza infection and narcolepsy is required. Narcolepsy is most commonly caused by a reduction or absence of hypocretin produced by hypocretin-secreting neurons in the hypothalamus, and is tightly associated with HLA-II DQB1*06:02. Consequently, research focusing on CD4(+) T-cell responses, building on the hypothesis that for disease development, T cells specific for antigen(s) from hypocretin neurons must be activated or reactivated, is considered essential. Therefore, the following key areas of research can be identified, (1) characterization of hypothetical narcolepsy-specific auto-immune CD4(+) T cells, (2) mapping epitopes of such T cells, and (3) evaluating potential mechanisms that would enable such cells to gain access to the hypothalamus. Addressing these questions could further our understanding of the potential links between narcolepsy and A(H1N1)pdm09 vaccination and/or infection. Of particular interest is that any evidence of a mimicry-based mechanism could also explain the association between narcolepsy and A(H1N1)pdm09 influenza infection.

  18. 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.

  19. "Trivalent influenza vaccination of healthy adults 3 years after the onset of swine-origin H1N1 pandemic: restricted immunogenicity of the new A/H1N1v constituent?".

    PubMed

    Allwinn, R; Bickel, M; Lassmann, C; Wicker, S; Friedrichs, I

    2013-04-01

    Influenza vaccination is advised annually to reduce the burden of influenza disease. For sufficient vaccine campaigns also a continuous adoption of influenza vaccines are necessary, due to particularly high genetic variability of influenza A virus. Therefore, we evaluate the effectiveness of the trivalent influenza vaccine 2010/2011, against influenza A (H1N1, H3N2) and influenza B. Immune response was investigated in paired sera from 92 healthcare workers with the hemagglutination inhibition assay (HI). Protective antibody levels (HI titer ≥40) were found after vaccination for influenza A/California/07/2009(H1N1): 84.71 % [GMT: 115.34]; for influenza A/Perth/16/2009(H3N2): 94.94 % [GMT: 268.47] and for influenza B/Brisbane/60/2008: 96.20 % [GMT: 176.83]; matching with the currently circulating virus strains. However, the highest seroprevalence rate was found against influenza B; pre- and post-vaccination titers as well, which may be due to comparatively high virus preservation. Remarkable, lowest seropositivity was seen against H1N1. Despite the significant titer rise, sufficient H1N1 herd immunity was still not achieved. It can be assumed that a high influenza A herd immunity may be a requirement for a successful booster vaccination.

  20. 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

  1. 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.

  2. Public willingness to take a vaccine or drug under Emergency Use Authorization during the 2009 H1N1 pandemic.

    PubMed

    Quinn, Sandra Crouse; Kumar, Supriya; Freimuth, Vicki S; Kidwell, Kelley; Musa, Donald

    2009-09-01

    On April 26, 2009, the United States declared a public health emergency in response to a growing but uncertain threat from H1N1 influenza, or swine flu. In June, the World Health Organization declared a pandemic. In the U.S., hospitalizations due to swine flu numbered 6,506 on August 6, 2009, with 436 deaths; all 50 states have reported cases. The declaration of a public health emergency, followed by the approval of multiple Emergency Use Authorizations (EUAs) by the Food and Drug Administration, allowed the distribution of unapproved drugs or the off-label use of approved drugs to the public. Thus far, there are 2 antiviral medications available to the public as EUA drugs. It is possible that an H1N1 vaccine will be initially released as an EUA in the fall in the first large-scale use of the EUA mechanism. This study explores the public's willingness to use a drug or vaccine under the conditions stipulated in the FDA's nonbinding guidance regarding EUAs. Using Knowledge Networks' panel, we conducted an internet survey with 1,543 adults from a representative sample of the U.S. population with 2 over samples of African Americans and Spanish-speaking Hispanics. Our completion rate was 62%. We examined willingness to accept an EUA drug or an H1N1 vaccine, the extent of worry associated with taking either, the conditions under which respondents would accept an EUA drug or vaccine, and the impact of language from the EUA fact sheets on people's willingness to accept a drug for themselves or their children. We also examined the association among these variables and race/ethnicity, education level, trust in government, previous vaccine acceptance, and perceived personal consequences from H1N1 influenza. These results provide critical insights into the challenges of communicating about EUA drugs and vaccine in our current pandemic.

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

    PubMed Central

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

    2011-01-01

    Please cite this paper as: Yin et al. (2011) Immunogenicity and safety of pandemic influenza A (H1N1) 2009 vaccine: systematic review and meta‐analysis. Influenza and Other Respiratory Viruses 5(5), 299–305. 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

  4. Immune response to 2009 H1N1 vaccine in HIV-infected adults in Northern Thailand

    PubMed Central

    Chotirosniramit, Nuntisa; Sugandhavesa, Patcharaphan; Aurpibul, Linda; Thetket, Sunida; Kosashunhanan, Natthapol; Supindham, Taweewat; Wongkulab, Panuwat; Kaewpoowat, Quanhathai; Chaiklang, Kanokporn; Kaewthip, Oranitcha; Sroysuwan, Piyathida; Wongthanee, Antika; Lerdsamran, Hatairat; Puthavathana, Pilaipan; Suparatpinyo, Khuanchai

    2012-01-01

    Background: In late 2009, the Thai Ministry of Public Health provided two million doses of the monovalent pandemic influenza H1N1 2009 vaccine (Panenza® Sanofi Pasteur), which was the only vaccine formulation available in Thailand, to persons at risk of more severe manifestations of the disease including HIV infection. Several studies have shown poorer immune responses to the 2009 H1N1 vaccines in HIV-infected individuals. There are limited data in this population in resource-limited countries. Results: At day 28 post-vaccination, seroconversion was found in 32.0% (95%CI 24.5 - 40.2) of the HIV-infected group and 35.0% (95%CI 15.4- 59.2) of the healthy controls (p = 0.79). Seroprotection rate was observed in 33.3% (95%CI 25.8–41.6) and 35.0% (95%CI 15.4–59.2) of the HIV-infected group and the control group, respectively (p = 0.88). Among HIV-infected participants, the strongest factor associated with vaccine response was age 42 y or younger (p = 0.05). Methods: We evaluated the immunogenicity of a single, 15µg/0.5ml dose of a monovalent, non-adjuvanted 2009 H1N1 vaccine in 150 HIV-infected Thai adults and 20 healthy controls. Immunogenicity was measured by hemagglutination inhibition assay (HI) at baseline and 28 d after vaccination. Seroconversion was defined as 1) pre-vaccination HI titer < 1:10 and post-vaccination HI titer ≥ 1:40, or 2) pre-vaccination HI titer ≥ 1:10 and a minimum of 4-fold rise in post-vaccination HI titer. Seroprotection was defined as a post-vaccination HI titer of ≥ 1:40. Conclusions: A low seroconversion rate to the 2009 H1N1 vaccine in both study groups, corresponding with data from trials in the region, may suggest that the vaccine used in our study is not very immunogenic. Further studies on different vaccines, dosing, adjuvants, or schedule strategies may be needed to achieve effective immunization in HIV-infected population. PMID:22906932

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

    DTIC Science & Technology

    2010-05-01

    severe) outcomes and warrants further investigation. Our findings further complement recent reports among civilian populations in Mexico [13,14] and among...et al. (2009) Infection and death from influenza A H1N1 virus in Mexico : a retrospective analysis. Lancet 374: 2072–2079. 14. Garcia-Garcia L...Valdespino-Gomez JL, Lazcano-Ponce E, Jimenez-Corona A, Higuera- Iglesias A, et al. (2009) Partial protection of seasonal trivalent inactivated vaccine

  6. A novel sequence-based antigenic distance measure for H1N1, with application to vaccine effectiveness and the selection of vaccine strains

    PubMed Central

    Pan, Keyao; Subieta, Krystina C.; Deem, Michael W.

    2011-01-01

    H1N1 influenza causes substantial seasonal illness and was the subtype of the 2009 influenza pandemic. Precise measures of antigenic distance between the vaccine and circulating virus strains help researchers design influenza vaccines with high vaccine effectiveness. We here introduce a sequence-based method to predict vaccine effectiveness in humans. Historical epidemiological data show that this sequence-based method is as predictive of vaccine effectiveness as hemagglutination inhibition assay data from ferret animal model studies. Interestingly, the expected vaccine effectiveness is greater against H1N1 than H3N2, suggesting a stronger immune response against H1N1 than H3N2. The evolution rate of hemagglutinin in H1N1 is also shown to be greater than that in H3N2, presumably due to greater immune selection pressure. PMID:21123189

  7. Italian post-marketing surveillance for adverse event reports after MF59-adjuvanted H1N1v vaccination.

    PubMed

    Parretta, Elisabetta; Ianniello, Benedetta; Ferrazin, Fernanda; Rossi, Francesco; Capuano, Annalisa

    2011-05-09

    According to European recommendations, the Italian Medicines Agency (AIFA) required close monitoring of the safety of the MF59-adjuvanted H1N1v vaccine, which was the only vaccine available in Italy for prophylaxis of the A/H1N1 (2009) pandemic influenza. From October 2009 to June 2010, the Italian Pharmacovigilance Adverse Event (AE) Spontaneous Reporting System [Rete Nazionale Farmacovigilanza] (RNF) received 1330 reports of AEs temporally related with the pandemic influenza vaccination out of a total of 924,057 doses administered. Among these, 1,162 (87.37%) AE reports were classified 'non serious', 91 (6.84%) 'serious', 3 (0.23%) had a fatal outcome and 74 (5.56%) did not include the degree of seriousness. Among the serious AE reports, some unexpected AEs emerged. Even though some typical vaccine safety issues which emerged should be further explored, such as vaccination in pregnancy, the analysis of all AE reports sent to RNF shows that the vaccine has a well-tolerated safety profile which resembles that of the already available seasonal influenza vaccines. This contrasts with the widespread public concern about its safety, which has been one of the major causes of the low vaccination rate observed in Italy, as well as in other countries.

  8. What the Public Was Saying about the H1N1 Vaccine: Perceptions and Issues Discussed in On-Line Comments during the 2009 H1N1 Pandemic

    PubMed Central

    Henrich, Natalie; Holmes, Bev

    2011-01-01

    During the 2009 H1N1 pandemic, a vaccine was made available to all Canadians. Despite efforts to promote vaccination, the public's intent to vaccinate remained low. In order to better understand the public's resistance to getting vaccinated, this study addressed factors that influenced the public's decision making about uptake. To do this, we used a relatively novel source of qualitative data – comments posted on-line in response to news articles on a particular topic. This study analysed 1,796 comments posted in response to 12 articles dealing with H1N1 vaccine on websites of three major Canadian news sources. Articles were selected based on topic and number of comments. A second objective was to assess the extent to which on-line comments can be used as a reliable data source to capture public attitudes during a health crisis. The following seven themes were mentioned in at least 5% of the comments (% indicates the percentage of comments that included the theme): fear of H1N1 (18.8%); responsibility of media (17.8%); government competency (17.7%); government trustworthiness (10.7%); fear of H1N1 vaccine (8.1%); pharmaceutical companies (7.6%); and personal protective measures (5.8%). It is assumed that the more frequently a theme was mentioned, the more that theme influenced decision making about vaccination. These key themes for the public were often not aligned with the issues and information officials perceived, and conveyed, as relevant in the decision making process. The main themes from the comments were consistent with results from surveys and focus groups addressing similar issues, which suggest that on-line comments do provide a reliable source of qualitative data on attitudes and perceptions of issues that emerge in a health crisis. The insights derived from the comments can contribute to improved communication and policy decisions about vaccination in health crises that incorporate the public's views. PMID:21533161

  9. 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

  10. Pandemic influenza A (H1N1) in non-vaccinated, pregnant women in Spain (2009-2010).

    PubMed

    Morales-Suárez-Varela, María; González-Candelas, Fernando; Astray, Jenaro; Alonso, Jordi; Castro, Ady; Cantón, Rafael; Galán, Juan Carlos; Garin, Olatz; Soldevila, Núria; Baricot, Maretva; Castilla, Jesús; Godoy, Pere; Delgado-Rodríguez, Miguel; Martín, Vicente; Mayoral, José María; Pumarola, Tomás; Quintana, José Maria; Tamames, Sonia; Llopis-González, Agustín; Domínguez, Angela

    2014-08-01

    The aim of this study was to investigate the main characteristics of non-vaccinated pregnant women who were hospitalised for influenza A (H1N1) pdm09 pandemic versus pregnant women hospitalised for non-influenza-related reasons in Spain, and to characterise the clinical presentation of the disease in this population to facilitate early diagnosis and future action programmes. Understanding influenza infection during pregnancy is important as pregnant women are a high-risk population for increased morbidity from influenza infection. We investigated the socio-demographic and clinical features of 51 non-vaccinated, pregnant women infected with the pandemic influenza A (H1N1) virus in Spain (cases) and compared them to 114 controls (non-vaccinated and non-infected pregnant women) aged 15-44 years. Substantial and significant odd ratios (ORs) for pandemic influenza A (H1N1) were found for the pregnant women who were obese compared with controls (body mass index > 30) (OR 3.03; 95% confidence intervals 1.13-8.11). The more prevalent symptoms observed in pandemic influenza-infected pregnant women were high temperature, cough (82.4%), malaise (80.5%), myalgia (56.1%), and headaches (54.9%). Our results suggest that the initial symptoms and risk factors for infection of pregnant women with the influenza A (H1N1) pdm09 virus are similar to the symptoms and risk factors for seasonal influenza, which make early diagnosis difficult, and reinforces the need to identify and protect high-risk groups.

  11. 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

  12. Determinants of Refusal of A/H1N1 Pandemic Vaccination in a High Risk Population: A Qualitative Approach

    PubMed Central

    d'Alessandro, Eugenie; Hubert, Dominique; Launay, Odile; Bassinet, Laurence; Lortholary, Olivier; Jaffre, Yannick; Sermet-Gaudelus, Isabelle

    2012-01-01

    Background Our study analyses the main determinants of refusal or acceptance of the 2009 A/H1N1 vaccine in patients with cystic fibrosis, a high-risk population for severe flu infection, usually very compliant for seasonal flu vaccine. Methodology/Principal Findings We conducted a qualitative study based on semi-structured interviews in 3 cystic fibrosis referral centres in Paris, France. The study included 42 patients with cystic fibrosis: 24 who refused the vaccine and 18 who were vaccinated. The two groups differed quite substantially in their perceptions of vaccine- and disease-related risks. Those who refused the vaccine were motivated mainly by the fears it aroused and did not explicitly consider the 2009 A/H1N1 flu a potentially severe disease. People who were vaccinated explained their choice, first and foremost, as intended to prevent the flu's potential consequences on respiratory cystic fibrosis disease. Moreover, they considered vaccination to be an indirect collective prevention tool. Patients who refused the vaccine mentioned multiple, contradictory information sources and did not appear to consider the recommendation of their local health care provider as predominant. On the contrary, those who were vaccinated stated that they had based their decision solely on the clear and unequivocal advice of their health care provider. Conclusions/Significance These results of our survey led us to formulate three main recommendations for improving adhesion to new pandemic vaccines. (1) it appears necessary to reinforce patient education about the disease and its specific risks, but also general population information about community immunity. (2) it is essential to disseminate a clear and effective message about the safety of novel vaccines. (3) this message should be conveyed by local health care providers, who should be involved in implementing immunization. PMID:22506011

  13. Phase II Trial in Adults of Concurrent or Sequential 2009 Pandemic H1N1 and 2009-2010 Seasonal Trivalent Influenza Vaccinations

    PubMed Central

    Frey, Sharon E.; Bernstein, David I.; Brady, Rebecca C.; Keitel, Wendy A.; Sahly, Hana El; Rouphael, Nadine Georges; Mulligan, Mark J.; Atmar, Robert L.; Edupuganti, Srilatha; Patel, Shital M.; Dickey, Michelle; Graham, Irene; Anderson, Edwin L.; Noah, Diana L.; Hill, Heather; Wolff, Mark; Belshe, Robert B.

    2014-01-01

    Background During the 2009 influenza pandemic both seasonal and 2009 pandemic vaccines were recommended. We conducted a randomized trial of monovalent 2009-H1N1 vaccine and seasonal trivalent inactivated influenza vaccine (IIV3) given sequentially or concurrently to adults. Methods Adults randomized to 4 study groups and stratified by age (18-64 and ≥65 years) received 1 dose of seasonal IIV3 or placebo and 2 doses of 2009-H1N1 vaccine or placebo in one of 4 combinations, i.e., H1N1+Placebo/H1N1+Placebo/IIV3 (HP/HP/V3), H1N1+ IIV3/H1N1+Placebo/Placebo (HV3/HP/P), H1N1+Placebo/H1N1+ IIV3/Placebo (HP/HV3/P), and IIV3+Placebo/H1N1+Placebo/H1N1 (V3P/HP/H). Intramuscular injections were given three times at 21 day intervals. Sera for antibody assays were obtained prior to and 21 days after each vaccination. Reactogenicity and adverse events were monitored. Results Eight hundred-five (805) adults were enrolled. All combinations of vaccines were safe and well tolerated. In general, one dose of 2009-H1N1 and one dose of IIV3, regardless of sequence or concurrency of administration, were immunogenic in adults. There were no significant differences in geometric mean titers (GMT) or the proportions of subjects with ≥4-fold rise in antibody responses and titers ≥40 for any vaccine group or between age strata for 2009-H1N1 after the first or second dose, although the vaccine sequence affected the titers to the IIV3 antigens. Hemagglutination inhibition antibody (HAI) GMTs against 2009-H1N1 for the combined age strata 21 days after the first 2009-H1N1 dose were 190.4, 182.1, 232.9 and 157.5 for HP/HP/V3, HV3/HP/P, HP/HV3/P and V3P/HP/H, respectively. While IIV3 GMTs were adequate they were generally lower than the 2009-H1N1 GMTs. In a subset of subjects, there was good correlation between HAI and microneutralization (MN) titers (Spearman's correlation coefficient 0.92). Conclusions All vaccine combinations were generally well tolerated. Immune responses to one dose of 2009

  14. Determinants of Vaccine Immunogenicity in HIV-Infected Pregnant Women: Analysis of B and T Cell Responses to Pandemic H1N1 Monovalent Vaccine

    PubMed Central

    Weinberg, Adriana; Muresan, Petronella; Richardson, Kelly M.; Fenton, Terence; Dominguez, Teresa; Bloom, Anthony; Watts, D. Heather

    2015-01-01

    Influenza infections have high frequency and morbidity in HIV-infected pregnant women, underscoring the importance of vaccine-conferred protection. To identify the factors that determine vaccine immunogenicity in this group, we characterized the relationship of B- and T-cell responses to pandemic H1N1 (pH1N1) vaccine with HIV-associated immunologic and virologic characteristics. pH1N1 and seasonal-H1N1 (sH1N1) antibodies were measured in 119 HIV-infected pregnant women after two double-strength pH1N1 vaccine doses. pH1N1-IgG and IgA B-cell FluoroSpot, pH1N1- and sH1N1-interferon γ (IFNγ) and granzyme B (GrB) T-cell FluoroSpot, and flow cytometric characterization of B- and T-cell subsets were performed in 57 subjects. pH1N1-antibodies increased after vaccination, but less than previously described in healthy adults. pH1N1-IgG memory B cells (Bmem) increased, IFNγ-effector T-cells (Teff) decreased, and IgA Bmem and GrB Teff did not change. pH1N1-antibodies and Teff were significantly correlated with each other and with sH1N1-HAI and Teff, respectively, before and after vaccination. pH1N1-antibody responses to the vaccine significantly increased with high proportions of CD4+, low CD8+ and low CD8+HLADR+CD38+ activated (Tact) cells. pH1N1-IgG Bmem responses increased with high proportions of CD19+CD27+CD21- activated B cells (Bact), high CD8+CD39+ regulatory T cells (Treg), and low CD19+CD27-CD21- exhausted B cells (Bexhaust). IFNγ-Teff responses increased with low HIV plasma RNA, CD8+HLADR+CD38+ Tact, CD4+FoxP3+ Treg and CD19+IL10+ Breg. In conclusion, pre-existing antibody and Teff responses to sH1N1 were associated with increased responses to pH1N1 vaccination in HIV-infected pregnant women suggesting an important role for heterosubtypic immunologic memory. High CD4+% T cells were associated with increased, whereas high HIV replication, Tact and Bexhaust were associated with decreased vaccine immunogenicity. High Treg increased antibody responses but decreased

  15. Impact of information on intentions to vaccinate in a potential epidemic: Swine-origin Influenza A (H1N1).

    PubMed

    Chanel, Olivier; Luchini, Stéphane; Massoni, Sébastien; Vergnaud, Jean-Christophe

    2011-01-01

    Vaccination campaigns to prevent the spread of epidemics are successful only if the targeted populations subscribe to the recommendations of health authorities. However, because compulsory vaccination is hardly conceivable in modern democracies, governments need to convince their populations through efficient and persuasive information campaigns. In the context of the swine-origin A (H1N1) 2009 pandemic, we use an interactive study among the general public in the South of France, with 175 participants, to explore what type of information can induce change in vaccination intentions at both aggregate and individual levels. We find that individual attitudes to vaccination are based on rational appraisal of the situation, and that it is information of a purely scientific nature that has the only significant positive effect on intention to vaccinate.

  16. 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

  17. Immunization-Safety Monitoring Systems for the 2009 H1N1 Monovalent Influenza Vaccination Program

    DTIC Science & Technology

    2011-01-01

    Division of Infectious Diseases and Dept of Laboratory Medicine, Boston, MA; eImmunization Safety Office, Division of Healthcare Quality Promotion...Centers for Disease Control and Prevention, Atlanta, GA; fMilitary Vaccine Agency, United States Army, Falls Church, VA; gNational Center for Patient...Department of Defense VAERS—Vaccine Adverse Event Reporting System CDC—Centers for Disease Control and Prevention VSD—Vaccine Safety Datalink RCA—rapid cycle

  18. Immunohistochemical screening for antibodies in recent onset type 1 narcolepsy and after H1N1 vaccination.

    PubMed

    van der Heide, Astrid; Hegeman-Kleinn, Ingrid M; Peeters, Els; Lammers, Gert J; Fronczek, Rolf

    2015-06-15

    Narcolepsy type 1 patients typically have undetectable hypocretin-1 levels in the cerebrospinal fluid (CSF), as a result of a selective loss of the hypocretin containing neurons in the hypothalamus. An autoimmune attack targeting hypothalamic hypocretin (orexin) neurons is hypothesised. So far, no direct evidence for an autoimmune attack was found. One of the major limitations of previous studies was that none included patients close to disease onset. We screened serum of 21 narcolepsy type 1 patients close to disease onset (median 11 months), including 8 H1N1 vaccinated patients, for antibodies against hypocretin neurons using immunohistochemistry. No autoantibodies against hypocretin neurons could be detected.

  19. H1N1 Influenza Pandemic in Italy Revisited: Has the Willingness to Get Vaccinated Suffered in the Long Run?

    PubMed Central

    Ludolph, Ramona; Nobile, Marta; Hartung, Uwe; Castaldi, Silvana; Schulz, Peter J.

    2015-01-01

    Background The aim of the study is to assess the long-term secondary effects of personal experience with the H1N1 pandemic of 2009/2010 and the perception of the institutional reaction to it on Italians’ willingness to get vaccinated in case of a novel influenza pandemic. Design and Methods We conducted 140 face-to-face interviews in the Registry Office of the Municipality of Milan, Italy, from October to December 2012. Results Willingness to get vaccinated during a novel influenza pandemic was best predicted by having been vaccinated against the seasonal flu in the past (OR=5.18; 95%CI: 1.40 to 19.13) and fear of losing one’s life in case of an infection with H1N1 (OR=4.09; 95%CI: 1.68 to 9.97). It was unaffected by the assessment of institutional performance. Conclusions The findings of this study do not point to long-term secondary effects of the institutional handling of the H1N1 pandemic. The results highlight the fact that behavioural intention is not the same as behaviour, and that the former cannot simply be taken as an indicator of the latter. Significance for public health Whereas influenza pandemics occurred rather rarely in the last centuries, their frequency can be expected to increase in the future due to the enhanced globalisation and still raising importance of air travelling. Recent examples (Ebola, H1N1, SARS, avian influenza) demonstrate that initially local disease outbreaks often become worldwide health threats of international concern. National and international health authorities are consequently urged to present preparedness plans on how to manage such health crises. However, their success highly depends on their acceptance by the public. To ensure the public compliance with recommended actions, effective communication is needed. Since communication is most successful when it meets the needs of the target audience, a full understanding of the audience is crucial. This study can help public health experts to better understand the

  20. Impact of cytokine in type 1 narcolepsy: Role of pandemic H1N1 vaccination ?

    PubMed

    Lecendreux, Michel; Libri, Valentina; Jaussent, Isabelle; Mottez, Estelle; Lopez, Régis; Lavault, Sophie; Regnault, Armelle; Arnulf, Isabelle; Dauvilliers, Yves

    2015-06-01

    Recent advances in the identification of susceptibility genes and environmental exposures (pandemic influenza 2009 vaccination) provide strong support that narcolepsy type 1 is an immune-mediated disease. Considering the limited knowledge regarding the immune mechanisms involved in narcolepsy whether related to flu vaccination or not and the recent progresses in cytokine measurement technology, we assessed 30 cytokines, chemokines and growth factors using the Luminex technology in either peripheral (serum) or central (CSF) compartments in a large population of 90 children and adult patients with narcolepsy type 1 in comparison to 58 non-hypocretin deficient hypersomniacs and 41 healthy controls. Furthermore, we compared their levels in patients with narcolepsy whether exposed to pandemic flu vaccine or not, and analyzed the effect of age, duration of disease and symptom severity. Comparison for sera biomarkers between narcolepsy (n = 84, 54 males, median age: 15.5 years old) and healthy controls (n = 41, 13 males, median age: 20 years old) revealed an increased stimulation of the immune system with high release of several pro- and anti-inflammatory serum cytokines and growth factors with interferon-γ, CCL11, epidermal growth factor, and interleukin-2 receptor being independently associated with narcolepsy. Increased levels of interferon-γ, CCL11, and interleukin-12 were found when close to narcolepsy onset. After several adjustments, only one CSF biomarker differed between narcolepsy (n = 44, 26 males, median age: 15 years old) and non-hypocretin deficient hypersomnias (n = 57, 24 males, median age: 36 years old) with higher CCL 3 levels found in narcolepsy. Comparison for sera biomarkers between patients with narcolepsy who developed the disease post-pandemic flu vaccination (n = 36) to those without vaccination (n = 48) revealed an increased stimulation of the immune system with high release of three cytokines, regulated upon activation normal T-cell expressed

  1. Recipients of vaccine against the 1976 "swine flu" have enhanced neutralization responses to the 2009 novel H1N1 influenza virus.

    PubMed

    McCullers, Jonathan A; Van De Velde, Lee-Ann; Allison, Kim J; Branum, Kristen C; Webby, Richard J; Flynn, Patricia M

    2010-06-01

    BACKGROUND. The world is facing a novel H1N1 influenza pandemic. A pandemic scare with a similar influenza virus in 1976 resulted in the vaccination of nearly 45 million persons. We hypothesized that prior receipt of the 1976 "swine flu" vaccine would enhance immune responses to the 2009 novel H1N1 influenza strain. METHODS. A prospective, volunteer sample of employees aged > or = 55 years at a children's cancer hospital in August 2009 was assessed for antibody responses to the 2009 pandemic H1N1 influenza virus and the 2008-2009 seasonal H1N1 influenza virus. RESULTS. Antibody responses by hemagglutination-inhibition assay were high against both the seasonal influenza virus (89.7% had a titer considered seroprotective) and pandemic H1N1 influenza virus (88.8% had a seroprotective titer). These antibodies were effective at neutralizing the seasonal H1N1 influenza virus in 68.1% of participants (titer > or = 40), but only 18.1% had detectable neutralizing titers against the pandemic H1N1 influenza virus. Of 116 participants, 46 (39.7%) received the 1976 "swine flu" vaccine. Receipt of this vaccine significantly enhanced neutralization responses; 8 (17.4%) of 46 vaccine recipients had titers > or = 160, compared with only 3 (4.3%) of 70 who did not receive the vaccine (P = .018 by chi(2) test). CONCLUSIONS. In this cohort, persons aged > or = 55 years had evidence of robust immunity to the 2008-2009 seasonal H1N1 influenza virus. These antibodies were cross-reactive but nonneutralizing against the 2009 pandemic H1N1 influenza strain. Receipt of a vaccine to a related virus significantly enhanced the neutralization capacity of these responses, suggesting homologous vaccination against the 2009 pandemic H1N1 influenza virus would have a similar effect.

  2. Coordination Costs for School-Located Influenza Vaccination Clinics, Maine, 2009 H1N1 Pandemic

    ERIC Educational Resources Information Center

    Asay, Garrett R. Beeler; Cho, Bo-Hyun; Lorick, Suchita A.; Tipton, Meredith L.; Dube, Nancy L.; Messonnier, Mark L.

    2012-01-01

    School nurses played a key role in Maine's school-located influenza vaccination (SLV) clinics during the 2009-2010 pandemic season. The objective of this study was to determine, from the school district perspective, the labor hours and costs associated with outside-clinic coordination activities (OCA). The authors defined OCA as labor hours spent…

  3. Intent to receive influenza A (H1N1) 2009 monovalent and seasonal influenza vaccines - two counties, North Carolina, August 2009.

    PubMed

    2009-12-25

    On September 15, 2009, the Food and Drug Administration approved the manufacture of four influenza A (H1N1) 2009 monovalent vaccines. Before release of the first batches of the vaccine on September 30, intent to receive the vaccine was estimated at 50% among selected U.S. adult populations and as high as 70% for children. However, studies in previous years of seasonal influenza vaccination in children, who might require 2 doses based on age and prior vaccination status, have indicated poor compliance with recommendations. To measure intent to receive H1N1 and seasonal influenza vaccines among children and adults, during August 28-29, 2009, the North Carolina Center for Public Health Preparedness, with state and local public health officials, conducted a community assessment in two counties. This report summarizes the results of that assessment, which determined that 64% of adults reported intent to receive H1N1 vaccine. In addition, 65% of parents reported intent to have all their children (aged 6 months to <18 years) vaccinated with H1N1 vaccine, and 51% said they would have all their children vaccinated with both H1N1 and seasonal influenza vaccines. The most commonly reported reasons for not intending to receive H1N1 vaccine were belief in a low likelihood of infection (18%) and concern over vaccine side effects (14%); 85% of participants said they received their H1N1 information from television. To increase coverage with H1N1 and seasonal influenza vaccines, public health departments should use television to focus public health messages on the risks for infection and severe illness and the safety profile of the vaccine.

  4. [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

  5. Serologic cross reactivity of avian influenza H1 vaccinated commercial U.S. turkeys to the emergent H1N1 influenza virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Recently, the 2009 human H1N1 influenza virus was identified in turkey breeders in Chile, Canada and the U.S. resulting in infection and production losses. In these studies sera from turkeys vaccinated against avian influenza H1 were tested against the recent human pandemic H1N1 virus. Genetic ana...

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  7. 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

  8. Maintaining the momentum: Key factors influencing acceptance of influenza vaccination among pregnant women following the H1N1 pandemic

    PubMed Central

    Halperin, Beth A; MacKinnon-Cameron, Donna; McNeil, Shelly; Kalil, Jennifer; Halperin, Scott A

    2015-01-01

    This survey study compared pre- and post-pandemic knowledge, attitudes, beliefs, and intended behaviors of pregnant women regarding influenza vaccination (seasonal and/or pandemic) during pregnancy in order to determine key factors influencing their decision to adhere to influenza vaccine recommendations. Only 36% of 662 pre-pandemic respondents knew that influenza was more severe in pregnant women, compared to 62% of the 159 post-pandemic respondents. Of the pre-pandemic respondents, 41% agreed or strongly agreed that that it was safer to wait until after the first 3 months to receive the seasonal influenza vaccine, whereas 23% of the post-pandemic cohort agreed or strongly agreed; 32% of pre-pandemic participants compared to 11% of post-pandemic respondents felt it was best to avoid all vaccines while pregnant. Despite 61% of the pre-pandemic cohort stating that they would have the vaccine while pregnant if their doctor recommended it and 54% citing their doctor/nurse as their primary source of vaccine information, only 20% said their doctor discussed influenza vaccination during their pregnancy, compared to 77% of the post-pandemic respondents who reported having this conversation. Women whose doctors discussed influenza vaccine during pregnancy had higher overall knowledge scores (P < 0.0001; P = 0.005) and were more likely to believe the vaccine is safe in all stages of pregnancy (P < 0.0001; P = 0.001) than those whose doctors did not discuss influenza vaccination. The 2009 H1N1 pandemic experience appeared to change attitudes and behaviours of health care providers and their pregnant patients toward influenza vaccination. PMID:25668670

  9. Vaccine procurement during an influenza pandemic and the role of Advance Purchase Agreements: Lessons from 2009-H1N1.

    PubMed

    Turner, Mark

    2015-07-24

    Vaccines are hugely important tools in minimising the effect pandemic influenza could have on a population. The reforms introduced by the Pandemic Influenza Preparedness Framework are ill-suited to providing sufficient levels of access to vaccines to meet the needs of developing states, and as such developing states will continue to be reliant upon the traditional methods of vaccine procurement to procure the majority of the vaccines they required. Using procurement during 2009-H1N1 as a case study, this paper examines the methods of procurement utilised by states in order to determine if the procurement tools available to developing states are sufficient to procure adequate levels of pandemic influenza vaccines. Particular focus is given to the role Advance Purchase Agreements (APAs) play in the procurement process. By exploring this case study it is possible to argue that these procurement methods are ineffective for developing states, and when the next influenza pandemic occurs, demand will once again outstrip supply globally, due to supply of vaccines being dominated by the developed states with APAs in place.

  10. Seasonal Influenza A H1N1pdm09 Virus and Severe Outcomes: A Reason for Broader Vaccination in Non-Elderly, At-Risk People

    PubMed Central

    Omeñaca, Manuel; Panadero, Carolina; Royo, Laura; Vengoechea, Jose J.; Fandos, Sergio; de Pablo, Francisco; Bello, Salvador

    2016-01-01

    Background Recent pandemics of influenza A H1N1pdm09 virus have caused severe illness, especially in young people. Very few studies on influenza A H1N1pdm09 in post-pandemic periods exist, and there is no information on the severity of both seasonal influenza A(H1N1) and A(H3N2) from the same season, adjusting for potential confounders, including vaccine. Methods and Results We performed a retrospective observational study of adults hospitalized during the 2014 season with influenza A(H1N1) or A(H3N2). All patients underwent the same diagnostic and therapeutic protocol in a single hospital, including early Oseltamivir therapy. We included 234 patients: 146 (62.4%) influenza A(H1N1) and 88 (37.6%) A(H3N2). A(H1N1) patients were younger (p<0.01), developed more pneumonia (p<0.01), respiratory complications (p = 0.015), ARDS (p = 0.047), and septic shock (p = 0.049), were more frequently admitted to the ICU (p = 0.022), required IMV (p = 0.049), and were less frequently vaccinated (p = 0.008). After adjusting for age, comorbidities, time from onset of illness, and vaccine status, influenza A(H1N1) (OR, 2.525), coinfection (OR, 2.821), and no vaccination (OR, 3.086) were independent risk factors for severe disease. Conclusions Hospitalized patients with influenza A(H1N1) were more than twice as likely to have severe influenza. They were younger and most had not received the vaccine. Our findings suggest that seasonal influenza A(H1N1) maintains some features of pandemic viruses, and recommend wider use of vaccination in younger adult high-risk patients. PMID:27832114

  11. Atraumatic osteonecrosis of the humeral head after influenza A-(H1N1) v-2009 vaccination.

    PubMed

    Kuether, G; Dietrich, B; Smith, T; Peter, C; Gruessner, S

    2011-09-16

    In the recent pandemic influenza A-(H1N1) v-2009 vaccination campaign, adjuvanted vaccines have been used because of their antigen-sparing effect. According to available reports, the rate of severe vaccination reactions has not increased, as compared with previous seasonal influenza vaccinations. Here we describe an adult female patient who was vaccinated with an AS03 adjuvanted split-virus vaccine injected into the left arm. She experienced a prolonged and painful local reaction for 4 weeks. During this time, persistent incapacitating pain shifted into the left shoulder. Magnetic resonance imaging (MRI) at the injection site detected atraumatic humeral head osteonecrosis in conjunction with bursitis of the rotator cuff region. Clinical and laboratory examination revealed no other underlying disease. Using analgetic medication and physical therapy, resting pain completely remitted within the following 14 weeks. Pain on exertion declined within the following 6 months. Atraumatic osteonecrosis, a relatively rare disorder which initially presents non-specific clinical symptoms, has never been associated with parenteral influenza vaccination. Although the available data cannot establish a causal relationship, our patient's clinical course - with a continuous transition from increased local post-vaccination reactions to symptoms of a severe shoulder lesion with osteonecrosis - raises the question of a pathogenetic link. Considering the vascular pathogenesis of osteonecrosis, we hypothesize that our patient's enhanced local immunologic reaction may have led to regional vasculitis as the cause of bone destruction. As mild forms of osteonecrosis may have escaped previous clinical attention, it is the purpose of our report to increase awareness of this exceptional event as a possible side effect of parenteral adjuvanted vaccination.

  12. Surveillance for adverse events following receipt of pandemic 2009 H1N1 vaccine in the Post-Licensure Rapid Immunization Safety Monitoring (PRISM) System, 2009-2010.

    PubMed

    Yih, W Katherine; Lee, Grace M; Lieu, Tracy A; Ball, Robert; Kulldorff, Martin; Rett, Melisa; Wahl, Peter M; McMahill-Walraven, Cheryl N; Platt, Richard; Salmon, Daniel A

    2012-06-01

    The Post-Licensure Rapid Immunization Safety Monitoring (PRISM) system is a cohort-based active surveillance network initiated by the US Department of Health and Human Services to supplement preexisting and other vaccine safety monitoring systems in tracking the safety of monovalent pandemic 2009 H1N1 influenza vaccine in the United States during 2009-2010. PRISM investigators conducted retrospective analysis to determine whether 2009 H1N1 vaccination was associated with increased risk of any of 14 prespecified outcomes. Five health insurance and associated companies with 38 million members and 9 state/city immunization registries contributed records on more than 2.6 million doses of 2009 H1N1 vaccine. Data on outcomes came from insurance claims. Complementary designs (self-controlled risk interval, case-centered, and current-vs.-historical comparison) were used to optimize control for confounding and statistical power. The self-controlled risk interval analysis of chart-confirmed Guillain-Barré syndrome found an elevated but not statistically significant incidence rate ratio following receipt of inactivated 2009 H1N1 vaccine (incidence rate ratio = 2.50, 95% confidence interval: 0.42, 15.0) and no cases following live attenuated 2009 H1N1 vaccine. The study did not control for infection prior to Guillain-Barré syndrome, which may have been a confounder. The risks of other health outcomes of interest were generally not significantly elevated after 2009 H1N1 vaccination.

  13. Analysis of public responses to preparedness policies: the cases of H1N1 influenza vaccination and gas mask distribution

    PubMed Central

    2013-01-01

    Background During several months in 2009–2010, the Israeli population was asked to take part in two preparedness programs: Acquisition of gas masks against a potential chemical-warfare attack, and vaccination against the A/H1N1 influenza pandemics. Compliance with the first request was moderate and did not attract much attention, whereas compliance with the second request was very low and was accompanied by significant controversy. The aims of this study are to compare the public’s attitudes towards these two preparedness campaigns, and to explore the roles of trust, reasoned assessment, and reflexive reactions in the public’s response to governmental preparedness policies. Methods The comparative analysis was based on a telephone survey of 2,018 respondents representing a cross-section of the adult Israeli population. Univariate analysis to describe associations of public response and attitude was performed by Chi-square tests. Findings A set of queries related to actual compliance, trust in credibility of authorities, personal opinions, reasons for non-compliance, and attitudes towards uncertainties was used to characterize the response to mask-acquisition and vaccination. In the case of mask-acquisition, the dominant response profile was of trusting compliance based on non-conditional belief in the need to adhere to the recommendation (35.6% of respondents). In the case of vaccination, the dominant response profile was of trusting non-compliance based on a reflective belief in the need for adherence (34.8% of respondents). Among the variables examined in the study, passivity was found to be the major reason for non-compliance with mask-acquisition, whereas reasoned assessment of risk played a major role in non-compliance with vaccination. Realization of the complexity in dealing with uncertainty related to developing epidemics and to newly-developed vaccines was identified in the public’s response to the H1N1 vaccination campaign. Conclusions The newly

  14. [Immunogenicity of inactivated subunit adsorbed monovalent vaccine against influenza A/California/7/2009 (H1N1) strain].

    PubMed

    Zverev, V V; Kostinov, M P; Mikhailova, N A; Zhirova, S N; Mironov, A N; Terkacheva, O A; Romanova, A A; Cherdantsev, A P

    2011-01-01

    The immunogenicity of Pandeflu subunit vaccine against influenza A/California/7/2009 (H1N1) was evaluated in 70 healthy volunteers aged 18 to 60 years. The vaccine was intramuscularly injected twice at an interval of 28 days. Each dose (0.5 ml) contains A(HIN1) influenza virus hemagglutinin (15 +/- 2.2 microg), aluminum hydroxide (Denmark) (0.475 +/- 0.075 microg), and the preservative thiomerosal (merthiolate) (50 +/- 7.5 microg). The level of antibodies was determined in the microneutralization assay. After administration of two doses of the vaccine at a 28-day interval, the geometric mean antibody titer (GMAT) reached 1:21.1 with a further increase to 1:30 (the baseline GMAT) was 1:6.1). The frequencies of seroconversion and seroprotection were 71.4 and 59.2%, respectively; the antibody increase factor was 4.92, which meets the CPMP criteria. The administration of the vaccine did not result in adverse reactions in the postvaccination period.

  15. 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…

  16. 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

  17. 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

    2017-02-28

    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.

  18. Cytophagic histiocytic panniculitis after H1N1 vaccination: a case report and review of the cutaneous side effects of influenza vaccines.

    PubMed

    Pauwels, C; Livideanu, C Bulai; Maza, A; Lamant, L; Paul, C

    2011-01-01

    Cytophagic histiocytic panniculitis (CHP) is a rare disease mostly caused by viral infections and/or lymphoproliferative diseases. We describe a case of CHP associated with H1N1 vaccine during the winter 2009-2010 vaccination campaign and discuss the cutaneous side effects of influenza vaccines. A 6-year-old child presented with inflammatory subcutaneous nodules, which had appeared 1 month after the first injection of H1N1 vaccine and 1 week after the second injection. There was no history of recent infection. The skin lesions spontaneously disappeared without scarring. In CHP the abnormal cytokine secretion from neoplastic or reactive T cells promotes monocyte-macrophage activation and haemophagocytosis. Vaccination is not a common cause of CHP, but it seems possible that, as in infectious diseases, reactive T cells to the vaccine antigen could trigger CHP.

  19. Interim estimates of 2015/16 vaccine effectiveness against influenza A(H1N1)pdm09, Canada, February 2016.

    PubMed

    Chambers, Catharine; Skowronski, Danuta M; Sabaiduc, Suzana; Winter, Anne Luise; Dickinson, James A; De Serres, Gaston; Gubbay, Jonathan B; Drews, Steven J; Martineau, Christine; Eshaghi, Alireza; Krajden, Mel; Bastien, Nathalie; Li, Yan

    2016-01-01

    Using a test-negative design, the Canadian Sentinel Practitioner Surveillance Network (SPSN) assessed interim 2015/16 vaccine effectiveness (VE) against influenza A(H1N1)pdm09 viruses. Adjusted VE showed significant protection of 64% (95% confidence interval (CI): 44-77%) overall and 56% (95%CI: 26-73%) for adults between 20 and 64 years-old against medically attended, laboratory-confirmed A(H1N1)pdm09 illness. Among the 67 A(H1N1)pdm09-positive specimens that were successfully sequenced, 62 (> 90%) belonged to the emerging genetic 6B.1 subclade, defined by S162N (potential gain of glycosylation) and I216T mutations in the haemagglutinin protein. Findings from the Canadian SPSN indicate that the 2015/16 northern hemisphere vaccine provided significant protection against A(H1N1)pdm09 illness despite genetic evolution in circulating viruses.

  20. A Qualitative Study of Vaccine Acceptability and Decision Making among Pregnant Women in Morocco during the A (H1N1) pdm09 Pandemic

    PubMed Central

    Lohiniva, Anna-Leena; Barakat, Amal; Dueger, Erica; Restrepo, Suzanne; El Aouad, Rajae

    2014-01-01

    Vaccination uptake of pregnant women in Morocco during the A (H1N1) pdm09 pandemic was lower than expected. A qualitative study using open-ended questions was developed to explore the main determinants of acceptance and non-acceptance of the monovalent A (H1N1) pdm09 vaccine among pregnant women in Morocco and to identify information sources that influenced their decision-making process. The study sample included 123 vaccinated and unvaccinated pregnant women who were in their second or third trimester between December 2009 and March 2010. They took part in 14 focus group discussions and eight in-depth interviews in the districts of Casablanca and Kenitra. Thematic qualitative analysis identified reasons for vaccine non-acceptance: (1) fear of the monovalent A (H1N1) pdm09 vaccine, (2) belief in an A (H1N1) pdm09 pandemic conspiracy, (3) belief in the inapplicability of the monovalent A (H1N1) pdm09 vaccine to Moroccans, (4) lack of knowledge of the monovalent A (H1N1) pdm09 vaccine, and (5) challenges of vaccination services/logistics. Reasons for vaccine acceptance included: (1) perceived benefits and (2) modeling. Decision-making was strongly influenced by family, community, mass media, religious leaders and health providers suggesting that broad communication efforts should also be used to advocate for vaccination. Meaningful communication for future vaccine campaigns must consider these context-specific findings. As cultural and religious values are shared across many Arab countries, these findings may also provide valuable insights for seasonal influenza vaccine planning in the Middle East and North Africa region at large. PMID:25313555

  1. Relation of activation-induced deaminase (AID) expression with antibody response to A(H1N1)pdm09 vaccination in HIV-1 infected patients.

    PubMed

    Cagigi, Alberto; Pensieroso, Simone; Ruffin, Nicolas; Sammicheli, Stefano; Thorstensson, Rigmor; Pan-Hammarström, Qiang; Hejdeman, Bo; Nilsson, Anna; Chiodi, Francesca

    2013-04-26

    The relevance of CD4+T-cells, viral load and age in the immunological response to influenza infection and vaccination in HIV-1 infected individuals has previously been pointed out. Our study aimed at assessing, in the setting of 2009 A(H1N1)pdm09 influenza vaccination, whether quantification of activation-induced deaminase (AID) expression in blood B-cells may provide additional indications for predicting antibody response to vaccination in HIV-1 infected patients with similar CD4+T-cell counts and age. Forty-seven healthy controls, 37 ART-treated and 17 treatment-naïve HIV-1 infected patients were enrolled in the study. Blood was collected prior to A(H1N1)pdm09 vaccination and at 1, 3 and 6 months after vaccination. Antibody titers to A(H1N1)pdm09 vaccine were measured by hemagglutination inhibition (HI) assay while the mRNA expression levels of AID were measured by quantitative real time PCR. Upon B-cell activation in vitro, AID increase correlated to antibody response to the A(H1N1)pdm09 vaccine at 1 month after vaccination in all individuals. In addition, the maximum expression levels of AID were significantly higher in those individuals who still carried protective levels of A(H1N1)pdm09 antibodies after 6 months from vaccination. No correlation was found between CD4+T-cell counts or age at vaccination or HIV-1 viral load and levels of A(H1N1)pdm09 antibodies. Assessing AID expression before vaccination may be an additional useful tool for defining a vaccination strategy in immune-compromised individuals at risk of immunization failure.

  2. Characterization of Functional Antibody and Memory B-Cell Responses to pH1N1 Monovalent Vaccine in HIV-Infected Children and Youth

    PubMed Central

    Curtis, Donna J.; Muresan, Petronella; Nachman, Sharon; Fenton, Terence; Richardson, Kelly M.; Dominguez, Teresa; Flynn, Patricia M.; Spector, Stephen A.; Cunningham, Coleen K.; Bloom, Anthony; Weinberg, Adriana

    2015-01-01

    Objectives We investigated immune determinants of antibody responses and B-cell memory to pH1N1 vaccine in HIV-infected children. Methods Ninety subjects 4 to <25 years of age received two double doses of pH1N1 vaccine. Serum and cells were frozen at baseline, after each vaccination, and at 28 weeks post-immunization. Hemagglutination inhibition (HAI) titers, avidity indices (AI), B-cell subsets, and pH1N1 IgG and IgA antigen secreting cells (ASC) were measured at baseline and after each vaccination. Neutralizing antibodies and pH1N1-specific Th1, Th2 and Tfh cytokines were measured at baseline and post-dose 1. Results At entry, 26 (29%) subjects had pH1N1 protective HAI titers (≥1:40). pH1N1-specific HAI, neutralizing titers, AI, IgG ASC, IL-2 and IL-4 increased in response to vaccination (p<0.05), but IgA ASC, IL-5, IL-13, IL-21, IFNγ and B-cell subsets did not change. Subjects with baseline HAI ≥1:40 had significantly greater increases in IgG ASC and AI after immunization compared with those with HAI <1:40. Neutralizing titers and AI after vaccination increased with older age. High pH1N1 HAI responses were associated with increased IgG ASC, IFNγ, IL-2, microneutralizion titers, and AI. Microneutralization titers after vaccination increased with high IgG ASC and IL-2 responses. IgG ASC also increased with high IFNγ responses. CD4% and viral load did not predict the immune responses post-vaccination, but the B-cell distribution did. Notably, vaccine immunogenicity increased with high CD19+CD21+CD27+% resting memory, high CD19+CD10+CD27+% immature activated, low CD19+CD21-CD27-CD20-% tissue-like, low CD19+CD21-CD27-CD20-% transitional and low CD19+CD38+HLADR+% activated B-cell subsets. Conclusions HIV-infected children on HAART mount a broad B-cell memory response to pH1N1 vaccine, which was higher for subjects with baseline HAI≥1:40 and increased with age, presumably due to prior exposure to pH1N1 or to other influenza vaccination/infection. The response

  3. Description of a large urban school-located 2009 pandemic H1N1 vaccination campaign, New York City 2009-2010.

    PubMed

    Narciso, Heather E; Pathela, Preeti; Morgenthau, Beth Maldin; Kansagra, Susan M; May, Linda; Scaccia, Allison; Zucker, Jane R

    2012-04-01

    In the spring of 2009, New York City (NYC) experienced the emergence and rapid spread of pandemic influenza A H1N1 virus (pH1N1), which had a high attack rate in children and caused many school closures. During the 2009 fall wave of pH1N1, a school-located vaccination campaign for elementary schoolchildren was conducted in order to reduce infection and transmission in the school setting, thereby reducing the impact of pH1N1 that was observed earlier in the year. In this paper, we describe the planning and outcomes of the NYC school-located vaccination campaign. We compared consent and vaccination data for three vaccination models (school nurse alone, school nurse plus contract nurse, team). Overall, >1,200 of almost 1,600 eligible schools participated, achieving 26.8% consent and 21.5% first-dose vaccination rates, which did not vary significantly by vaccination model. A total of 189,902 doses were administered during two vaccination rounds to 115,668 students at 998 schools included in the analysis; vaccination rates varied by borough, school type, and poverty level. The team model achieved vaccination of more children per day and required fewer vaccination days per school. NYC's campaign is the largest described school-located influenza vaccination campaign to date. Despite substantial challenges, school-located vaccination is feasible in large, urban settings, and during a public health emergency.

  4. Heterogeneity of T Cell Responses to Pandemic pH1N1 Monovalent Vaccine in HIV-Infected Pregnant Women

    PubMed Central

    Muresan, Petronella; Richardson, Kelly; Fenton, Terence; Dominguez, Teresa; Bloom, Anthony; Watts, D. Heather; Abzug, Mark J.; Nachman, Sharon A.; Levin, Myron J.

    2015-01-01

    Abstract 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. PMID:26322930

  5. Effectiveness of the monovalent influenza A(H1N1)2009 vaccine in Navarre, Spain, 2009-2010: cohort and case-control study.

    PubMed

    Castilla, Jesús; Morán, Julio; Martínez-Artola, Víctor; Fernández-Alonso, Mirian; Guevara, Marcela; Cenoz, Manuel García; Reina, Gabriel; Alvarez, Nerea; Arriazu, Maite; Elía, Fernando; Salcedo, Esther; Barricarte, Aurelio

    2011-08-11

    We defined a population-based cohort (596,755 subjects) in Navarre, Spain, using electronic records from physicians, to evaluate the effectiveness of the monovalent A(H1N1)2009 vaccine in preventing influenza in the 2009-2010 pandemic season. During the 9-week period of vaccine availability and circulation of the A(H1N1)2009 virus, 4608 cases of medically attended influenza-like illness (MA-ILI) were registered (46 per 1000 person-years). After adjustment for sociodemographic covariables, outpatient visits and major chronic conditions, vaccination was associated with a 32% (95% CI: 8-50%) reduction in the overall incidence of MA-ILI. In a test negative case-control analysis nested in the cohort, swabs from 633 patients were included, and 123 were confirmed for A(H1N1)2009 influenza. No confirmed case had received A(H1N1)2009 vaccine versus 9.6% of controls (p<0.001). The vaccine effectiveness in preventing laboratory-confirmed influenza was 89% (95% CI: 36-100%) after adjusting for age, health care setting, major chronic conditions and period. Pandemic vaccine was effective in preventing MA-ILI and confirmed cases of influenza A(H1N1)2009 in the 2009-2010 season.

  6. Partial protection of seasonal trivalent inactivated vaccine against novel pandemic influenza A/H1N1 2009: case-control study in Mexico City

    PubMed Central

    Garcia-Garcia, Lourdes; Valdespino-Gómez, Jose Luis; Lazcano-Ponce, Eduardo; Jimenez-Corona, Aida; Higuera-Iglesias, Anjarath; Cruz-Hervert, Pablo; Cano-Arellano, Bulmaro; Garcia-Anaya, Antonio; Ferreira-Guerrero, Elizabeth; Baez-Saldaña, Renata; Ferreyra-Reyes, Leticia; Ponce-de-León-Rosales, Samuel; Alpuche-Aranda, Celia; Rodriguez-López, Mario Henry; Perez-Padilla, Rogelio; Hernandez-Avila, Mauricio

    2009-01-01

    Objective To evaluate the association of 2008-9 seasonal trivalent inactivated vaccine with cases of influenza A/H1N1 during the epidemic in Mexico. Design Frequency matched case-control study. Setting Specialty hospital in Mexico City, March to May 2009. Participants 60 patients with laboratory confirmed influenza A/H1N1 and 180 controls with other diseases (not influenza-like illness or pneumonia) living in Mexico City or the State of Mexico and matched for age and socioeconomic status. Main outcome measures Odds ratio and effectiveness of trivalent inactivated vaccine against influenza A/H1N1. Results Cases were more likely than controls to be admitted to hospital, undergo invasive mechanical ventilation, and die. Controls were more likely than cases to have chronic conditions that conferred a higher risk of influenza related complications. In the multivariate model, influenza A/H1N1 was independently associated with trivalent inactivated vaccine (odds ratio 0.27, 95% confidence interval 0.11 to 0.66) and underlying conditions (0.15, 0.08 to 0.30). Vaccine effectiveness was 73% (95% confidence interval 34% to 89%). None of the eight vaccinated cases died. Conclusions Preliminary evidence suggests some protection from the 2008-9 trivalent inactivated vaccine against pandemic influenza A/H1N1 2009, particularly severe forms of the disease, diagnosed in a specialty hospital during the influenza epidemic in Mexico City. PMID:19808768

  7. Effectiveness and safety of the A-H1N1 vaccine in children: a hospital-based case–control study

    PubMed Central

    2011-01-01

    Objective To verify whether vaccination against the A-H1N1 virus in the paediatric population was effective in preventing the occurrence of influenza-like illness (ILI) or was associated with adverse events of special interest. Design, setting and patients A case–control analysis was performed as part of surveillance of children hospitalised through the emergency departments of eight paediatric hospitals/wards for ILI, neurological disorders, non-infectious muco-cutaneous diseases and vasculitis, thrombocytopaenia and gastroduodenal lesions. Results Among 736 children enrolled from November 2009 to August 2010, only 25 had been vaccinated with the pandemic vaccine. Out of 268 children admitted for a diagnosis compatible with the adverse events of special interest, six had received the A-H1N1 vaccine, although none of the adverse events occurred within the predefined risk windows. Only 35 children out of 244 admitted with a diagnosis of ILI underwent laboratory testing: 11 were positive and 24 negative for the A-H1N1 virus. None of the A-H1N1 positive children had received the pandemic vaccine. The OR of ILI associated with any influenza vaccination was 0.9 (95% CI 0.1 to 5.5). Conclusions The study provides additional information on the benefit–risk profile of the pandemic vaccine. No sign of risk associated with the influenza A-H1N1 vaccine used in Italy was found, although several limitations were observed: in Italy, pandemic vaccination coverage was low, the epidemic was almost over by mid December 2009 and the A-H1N1 laboratory test was performed only during the epidemic phase (in <10% of children). This study supports the importance of the existing network of hospitals for the evaluation of signals relevant to new vaccines and drugs. PMID:22021877

  8. Serologic response after vaccination against influenza (A/H1N1)pdm09 in children with renal disease receiving oral immunosuppressive drugs.

    PubMed

    Tanaka, Seiji; Saikusa, Tomoko; Katafuchi, Yuno; Ushijima, Kosuke; Ohtsu, Yasushi; Tsumura, Naoki; Ito, Yuhei

    2015-09-11

    A limited number of reports are available regarding the effect of the influenza vaccine in pediatric patients receiving steroid and immunosuppressant therapy. The influenza A(H1N1)pdm09 vaccine was administered to 15 children with renal disease who were receiving steroid and immunosuppressant therapy (treatment group) and 23 children with who were not receiving these drugs (non-treatment group). Titer transition of the hemagglutination inhibition antibody was compared between the 2 groups immediately before vaccination and 4 weeks and 6 months after vaccination. Multivariate analysis showed a significant correlation between geometric mean titer, SCR, and SPR with age, while no correlation was observed between treatment with immunosuppressant therapy and efficacy. No serious adverse reactions occurred after vaccination. This strain is not present in existing influenza vaccines, and A(H1N1)pdm09HA vaccination was administered alone in 2009. The children in this study had not previously been exposed to this strain. Therefore, we evaluated the effect of the A(H1N1)pdm09HA vaccine without the effects of vaccination or past infection with A(H1N1)pdm09HA or A(H3N2) vaccination in the previous year.

  9. [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

  10. A post-marketing surveillance study of a human live-virus pandemic influenza A (H1N1) vaccine (Nasovac (®) ) in India.

    PubMed

    Kulkarni, Prasad S; Raut, Sidram K; Dhere, Rajeev M

    2013-01-01

    A live attenuated pandemic H1N1 influenza vaccine was developed in India. A post marketing surveillance was conducted retrospectively in healthy individuals (³ 3 years) who were vaccinated intranasally around one year before. After consent, the subjects recorded adverse events developing within 42 days. Among 7565 individuals (3 - 85 years), a total of 81 solicited adverse reactions (1%) were reported in 49 subjects (0.65%). The reactions included mild to moderate respiratory symptoms. No H1N1 case was encountered during one year postvaccination. The data show the safety of the live attenuated influenza vaccine platform developed in India.

  11. Chart-confirmed guillain-barre syndrome after 2009 H1N1 influenza vaccination among the Medicare population, 2009-2010.

    PubMed

    Polakowski, Laura L; Sandhu, Sukhminder K; Martin, David B; Ball, Robert; Macurdy, Thomas E; Franks, Riley L; Gibbs, Jonathan M; Kropp, Garner F; Avagyan, Armen; Kelman, Jeffrey A; Worrall, Christopher M; Sun, Guoying; Kliman, Rebecca E; Burwen, Dale R

    2013-09-15

    Given the increased risk of Guillain-Barré Syndrome (GBS) found with the 1976 swine influenza vaccine, both active surveillance and end-of-season analyses on chart-confirmed cases were performed across multiple US vaccine safety monitoring systems, including the Medicare system, to evaluate the association of GBS after 2009 monovalent H1N1 influenza vaccination. Medically reviewed cases consisted of H1N1-vaccinated Medicare beneficiaries who were hospitalized for GBS. These cases were then classified by using Brighton Collaboration diagnostic criteria. Thirty-one persons had Brighton level 1, 2, or 3 GBS or Fisher Syndrome, with symptom onset 1-119 days after vaccination. Self-controlled risk interval analyses estimated GBS risk within the 6-week period immediately following H1N1 vaccination compared with a later control period, with additional adjustment for seasonality. Our results showed an elevated risk of GBS with 2009 monovalent H1N1 vaccination (incidence rate ratio = 2.41, 95% confidence interval: 1.14, 5.11; attributable risk = 2.84 per million doses administered, 95% confidence interval: 0.21, 5.48). This observed risk was slightly higher than that seen with previous seasonal influenza vaccines; however, additional results that used a stricter case definition (Brighton level 1 or 2) were not statistically significant, and our ability to account for preceding respiratory/gastrointestinal illness was limited. Furthermore, the observed risk was substantially lower than that seen with the 1976 swine influenza vaccine.

  12. Acceptance of a Vaccine Against Novel Influenza A (H1N1) Virus Among Health Care Workers in Two Major Cities in Mexico

    PubMed Central

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

    2010-01-01

    Background and Aims 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. Methods 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. Results 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. Conclusions 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. PMID:20304260

  13. Poly-γ-glutamic acid/chitosan nanogel greatly enhances the efficacy and heterosubtypic cross-reactivity of H1N1 pandemic influenza vaccine

    PubMed Central

    Yang, Jihyun; Shim, Sang-Mu; Nguyen, Thi Quyen; Kim, Eun-Ha; Kim, Kwang; Lim, Yong Taik; Sung, Moon-Hee; Webby, Richard; Poo, Haryoung

    2017-01-01

    In 2009, the global outbreak of an influenza pandemic emphasized the need for an effective vaccine adjuvant. In this study, we examined the efficacy of poly-γ-glutamic acid/chitosan (PC) nanogel as an adjuvant for the influenza vaccine. PC nanogel significantly enhanced antigen-specific cross-presentation and cytotoxic T lymphocyte (CTL) activity. Compared with alum, the protective efficacy of the pandemic H1N1 influenza (pH1N1) vaccine was substantially increased by PC nanogel, with increased hemagglutination-inhibition titers, CTL activity, and earlier virus clearance after homologous and heterosubtypic [A/Philippines/2/82 (H3N2)] virus challenges. However, CD8+ T cell-depleted mice displayed no protection against the heterosubtypic virus challenge after immunization with PC nanogel-adjuvanted pH1N1 vaccine. We also observed that using PC nanogel as a vaccine adjuvant had a dose-sparing effect and significantly enhanced the long-lasting protection of the pH1N1 vaccine. Together, these results suggest that PC nanogel is a promising vaccine adjuvant that could broadly prevent influenza virus infection. PMID:28322289

  14. Vaccine-associated enhanced respiratory disease does not interfere with the adaptive immune response following challenge with pandemic A/H1N1 2009.

    PubMed

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

    2013-10-01

    The implications of sequential prime and challenge with mismatched influenza A viruses is a concern in mammals, including humans. We evaluated the ability of pigs affected with vaccine-associated enhanced respiratory disease (VAERD) to generate a humoral immune response against the heterologous challenge virus inciting the VAERD. Vaccinated and challenged (V/C) pigs were administered an inactivated swine δ-cluster H1N2 (MN08) vaccine with an HA similar to pre-2009 seasonal human viruses and challenged with heterologous A(H1N1) pandemic 2009 (H1N1pdm09). Vaccination induced MN08-specific hemagglutination inhibition (HI) antibody but not cross-reacting H1N1pdm09 HI antibody. However, vaccinated pigs demonstrated significantly higher post-challenge anti-H1N1pdm09 serum neutralizing (SN) antibodies at 14 and 21 days post inoculation (dpi) compared to nonvaccinated, challenged pigs (NV/C), indicating a priming effect of the vaccine. Serum and lung whole virus anti-H1N1pdm09 IgG ELISA antibodies in the vaccinated group were significantly higher than the challenge only pigs at all-time points evaluated. Lung IgA ELISA antibodies to both antigens were detected at 2, 5, and 21 dpi in vaccine-primed pigs, contrasted against mucosal ELISA antibody responses detected only at 21 dpi in the naïve-challenged group. Collectively, vaccine-primed pigs demonstrated a robust humoral immune response and elevated local adaptive cytokine levels, indicating VAERD does not adversely affect the induction of an immune response to challenge with heterologous virus despite the severe clinical disease and underlying lung pathology. Thus, original antigenic sin does not appear to be a component of VAERD.

  15. Addressing the Vaccine Hesitancy Continuum: An Audience Segmentation Analysis of American Adults Who Did Not Receive the 2009 H1N1 Vaccine

    PubMed Central

    Ramanadhan, Shoba; Galarce, Ezequiel; Xuan, Ziming; Alexander-Molloy, Jaclyn; Viswanath, Kasisomayajula

    2015-01-01

    Understanding the heterogeneity of groups along the vaccine hesitancy continuum presents an opportunity to tailor and increase the impact of public engagement efforts with these groups. Audience segmentation can support these goals, as demonstrated here in the context of the 2009 H1N1 vaccine. In March 2010, we surveyed 1569 respondents, drawn from a nationally representative sample of American adults, with oversampling of racial/ethnic minorities and persons living below the United States Federal Poverty Level. Guided by the Structural Influence Model, we assessed knowledge, attitudes, and behaviors related to H1N1; communication outcomes; and social determinants. Among those who did not receive the vaccine (n = 1166), cluster analysis identified three vaccine-hesitant subgroups. Disengaged Skeptics (67%) were furthest from vaccine acceptance, with low levels of concern and engagement. The Informed Unconvinced (19%) were sophisticated consumers of media and health information who may not have been reached with information to motivate vaccination. The Open to Persuasion cluster (14%) had the highest levels of concern and motivation and may have required engagement about vaccination broadly. There were significant sociodemographic differences between groups. This analysis highlights the potential to use segmentation techniques to identify subgroups on the vaccine hesitancy continuum and tailor public engagement efforts accordingly. PMID:26350595

  16. Addressing the Vaccine Hesitancy Continuum: An Audience Segmentation Analysis of American Adults Who Did Not Receive the 2009 H1N1 Vaccine.

    PubMed

    Ramanadhan, Shoba; Galarce, Ezequiel; Xuan, Ziming; Alexander-Molloy, Jaclyn; Viswanath, Kasisomayajula

    2015-07-15

    Understanding the heterogeneity of groups along the vaccine hesitancy continuum presents an opportunity to tailor and increase the impact of public engagement efforts with these groups. Audience segmentation can support these goals, as demonstrated here in the context of the 2009 H1N1 vaccine. In March 2010, we surveyed 1569 respondents, drawn from a nationally representative sample of American adults, with oversampling of racial/ethnic minorities and persons living below the United States Federal Poverty Level. Guided by the Structural Influence Model, we assessed knowledge, attitudes, and behaviors related to H1N1; communication outcomes; and social determinants. Among those who did not receive the vaccine (n = 1166), cluster analysis identified three vaccine-hesitant subgroups. Disengaged Skeptics (67%) were furthest from vaccine acceptance, with low levels of concern and engagement. The Informed Unconvinced (19%) were sophisticated consumers of media and health information who may not have been reached with information to motivate vaccination. The Open to Persuasion cluster (14%) had the highest levels of concern and motivation and may have required engagement about vaccination broadly. There were significant sociodemographic differences between groups. This analysis highlights the potential to use segmentation techniques to identify subgroups on the vaccine hesitancy continuum and tailor public engagement efforts accordingly.

  17. Modifications in the polymerase genes of a swine-like triple-reassortant influenza virus to generate live attenuated vaccines against 2009 pandemic H1N1 viruses.

    PubMed

    Pena, Lindomar; Vincent, Amy L; Ye, Jianqiang; Ciacci-Zanella, Janice R; Angel, Matthew; Lorusso, Alessio; Gauger, Philip C; Janke, Bruce H; Loving, Crystal L; Perez, Daniel R

    2011-01-01

    On 11 June 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) virus is the predominant influenza virus strain in the human population. It has also crossed the species barriers and infected turkeys and swine in several countries. Thus, the development of a vaccine that is effective in multiple animal species is urgently needed. We have previously demonstrated that the introduction of temperature-sensitive mutations into the PB2 and PB1 genes of an avian H9N2 virus, combined with the insertion of a hemagglutinin (HA) tag in PB1, resulted in an attenuated (att) vaccine backbone for both chickens and mice. Because the new pandemic strain is a triple-reassortant (TR) virus, we chose to introduce the double attenuating modifications into a swine-like TR virus isolate, A/turkey/OH/313053/04 (H3N2) (ty/04), with the goal of producing live attenuated influenza vaccines (LAIV). This genetically modified backbone had impaired polymerase activity and restricted virus growth at elevated temperatures. In vivo characterization of two H1N1 vaccine candidates generated using the ty/04 att backbone demonstrated that this vaccine is highly attenuated in mice, as indicated by the absence of signs of disease, limited replication, and minimum histopathological alterations in the respiratory tract. A single immunization with the ty/04 att-based vaccines conferred complete protection against a lethal H1N1pdm virus infection in mice. More importantly, vaccination of pigs with a ty/04 att-H1N1 vaccine candidate resulted in sterilizing immunity upon an aggressive intratracheal challenge with the 2009 H1N1 pandemic virus. Our studies highlight the safety of the ty/04 att vaccine platform and its potential as a master donor strain for the generation of live attenuated vaccines for humans and livestock.

  18. 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

  19. High Vaccination Coverage among Children during Influenza A(H1N1)pdm09 as a Potential Factor of Herd Immunity

    PubMed Central

    Matsuoka, Toshihiko; Sato, Tomoki; Akita, Tomoyuki; Yanagida, Jiturou; Ohge, Hiroki; Kuwabara, Masao; Tanaka, Junko

    2016-01-01

    The objective of this study was to identify factors related to the expansion of infection and prevention of influenza A(H1N1)pdm09. A retrospective non-randomized cohort study (from June 2009 to May 2010) on influenza A(H1N1)pdm09 was conducted in a sample of residents from Hiroshima Prefecture, Japan. The cumulative incidence of the influenza A(H1N1)pdm09 and the pandemic vaccine effectiveness (VE) were estimated. The response rate was 53.5% (178,669/333,892). Overall, the odds ratio of non-vaccinated group to vaccinated group for cumulative incidence of influenza A(H1N1)pdm09 was 2.18 (95% confidence interval (CI): 2.13–2.23) and the VE was 43.9% (CI: 42.8–44.9). The expansion of infection, indicating the power of transmission from infected person to susceptible person, was high in the 7–15 years age groups in each area. In conclusion, results from this survey suggested that schoolchildren-based vaccination rate participates in determining the level of herd immunity to influenza and children might be the drivers of influenza transmission. For future pandemic preparedness, vaccination of schoolchildren may help to prevent disease transmission during influenza outbreak. PMID:27763532

  20. High Vaccination Coverage among Children during Influenza A(H1N1)pdm09 as a Potential Factor of Herd Immunity.

    PubMed

    Matsuoka, Toshihiko; Sato, Tomoki; Akita, Tomoyuki; Yanagida, Jiturou; Ohge, Hiroki; Kuwabara, Masao; Tanaka, Junko

    2016-10-17

    The objective of this study was to identify factors related to the expansion of infection and prevention of influenza A(H1N1)pdm09. A retrospective non-randomized cohort study (from June 2009 to May 2010) on influenza A(H1N1)pdm09 was conducted in a sample of residents from Hiroshima Prefecture, Japan. The cumulative incidence of the influenza A(H1N1)pdm09 and the pandemic vaccine effectiveness (VE) were estimated. The response rate was 53.5% (178,669/333,892). Overall, the odds ratio of non-vaccinated group to vaccinated group for cumulative incidence of influenza A(H1N1)pdm09 was 2.18 (95% confidence interval (CI): 2.13-2.23) and the VE was 43.9% (CI: 42.8-44.9). The expansion of infection, indicating the power of transmission from infected person to susceptible person, was high in the 7-15 years age groups in each area. In conclusion, results from this survey suggested that schoolchildren-based vaccination rate participates in determining the level of herd immunity to influenza and children might be the drivers of influenza transmission. For future pandemic preparedness, vaccination of schoolchildren may help to prevent disease transmission during influenza outbreak.

  1. Efficacy of Inactivated Swine Influenza Virus Vaccines Against the 2009 A/H1N1 Influenza Virus in Pigs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The gene constellation of the 2009 pandemic A/H1N1 virus is a unique combination from swine influenza A viruses (SIV) of North American and Eurasian lineages, but prior to April 2009 had never before been identified in swine or other species. Although its hemagglutinin gene is related to North Ameri...

  2. Efficacy of Inactivated Swine Influenza Virus Vaccines Against 2009 H1N1 Influenza Virus in Pigs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Introduction. The gene constellation of the 2009 pandemic H1N1 virus is a unique combination from swine influenza A viruses (SIV) of North American and Eurasian lineages, but prior to April 2009 had never before been identified in swine or other species (1). Although its hemagglutinin gene is relat...

  3. Success of program linking data sources to monitor H1N1 vaccine safety points to potential for even broader safety surveillance.

    PubMed

    Salmon, Daniel; Yih, W Katherine; Lee, Grace; Rosofsky, Robert; Brown, Jeffrey; Vannice, Kirsten; Tokars, Jerome; Roddy, James; Ball, Robert; Gellin, Bruce; Lurie, Nicole; Koh, Howard; Platt, Richard; Lieu, Tracy

    2012-11-01

    In response to the 2009 H1N1 pandemic and subsequent vaccination program, the Department of Health and Human Services and collaborators developed the Post-Licensure Rapid Immunization Safety Monitoring (PRISM) Program as a demonstration project to detect rare adverse events rapidly. The program monitored three million people who had received the H1N1 vaccine by linking data from large private health plans and from public immunization registries that had originally not been designed to share data, and on a larger scale than had been previously attempted. The program generated safety data in two weeks rather than three to six monty 10ths-the standard time frame achievable using health plan data. PRISM substantially contributed to the understanding of the safety of H1N1 vaccines. Its use in the case of H1N1 highlights the necessity of proactive planning, scalable infrastructure, and public-private partnerships in tracking adverse events after vaccination in epidemics. It also illustrates how data could be integrated to produce policy-relevant information for other medical products.

  4. Serologic cross reactivity of serum samples from avian influenza vaccinated commercial U.S. turkeys to the emergent H1N1 influenza virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Recently, the 2009 human H1N1 influenza virus was identified in turkey breeders in Chile and Canada resulting in infection and egg production losses. In the U.S., vaccination of turkeys against avian influenza may include H1 and H3 viruses also isolated from swine. We tested whether sera from turk...

  5. In vitro assessment of the allergenicity of novel MF59-adjuvanted pandemic H1N1 influenza vaccine produced in dog kidney cells.

    PubMed

    Bencharitiwong, Ramon; Leonard, Stephanie; Tsai, Theodore; Nowak-Węgrzyn, Anna

    2012-07-01

    A licensed inactivated MF59-adjuvanted seasonal influenza vaccine (Optaflu) produced in canine kidney cells (MDCK 33016-PF) contained no egg proteins and did not trigger degranulation in rat basophilic leukemia (RBL) cells passively sensitized with human anti-dog IgE, supporting its safe use in dog-allergic individuals. The cell-derived pandemic H1N1 influenza vaccine was also adjuvanted with the emulsion adjuvant MF59, and support for its similar safe use was sought. We sought to evaluate in vitro allergenicity of the MF59-adjuvanted cell-derived pandemic H1N1 influenza vaccine in subjects with dog allergy, with a mediator release assay. RBL-2H3 cells transfected with human Fcε receptor type 1 were sensitized with sera from adult dog-allergic subjects and stimulated with serial dilutions of pandemic H1N1 influenza vaccine and dog dander extract. β-N-hexosaminidase release (NHR) was used as a marker of RBL degranulation.. Median dog dander-specific IgE in 30 dog-allergic subjects was 27.7 kU(A)/L (range 10.1; > 100); and in 5 dog non-allergic subjects was < 0.35 kU(A)/L (UniCAP system). Median (range) maximum NHR in dog-allergic subjects was: pandemic H1N1 influenza vaccine 1.1% (0; 4.4) and dog dander 6.9% (0.7; 37.3), P < 0.001. In conclusion, MF59-adjuvanted pandemic H1N1 influenza vaccine produced in continuous canine kidney cells did not trigger degranulation in RBL cells passively sensitized with human anti-dog IgE, supporting its safe use in dog-allergic individuals.

  6. Conservation and Diversity of Influenza A H1N1 HLA-Restricted T Cell Epitope Candidates for Epitope-Based Vaccines

    PubMed Central

    Tan, Paul ThiamJoo; Heiny, A. T.; Miotto, Olivo; Salmon, Jerome; Marques, Ernesto T. A.; Lemonnier, Francois; August, J. Thomas

    2010-01-01

    Background The immune-related evolution of influenza viruses is exceedingly complex and current vaccines against influenza must be reformulated for each influenza season because of the high degree of antigenic drift among circulating influenza strains. Delay in vaccine production is a serious problem in responding to a pandemic situation, such as that of the current H1N1 strain. Immune escape is generally attributed to reduced antibody recognition of the viral hemagglutinin and neuraminidase proteins whose rate of mutation is much greater than that of the internal non-structural proteins. As a possible alternative, vaccines directed at T cell epitope domains of internal influenza proteins, that are less susceptible to antigenic variation, have been investigated. Methodology/Principal Findings HLA transgenic mouse strains expressing HLA class I A*0201, A*2402, and B*0702, and class II DRB1*1501, DRB1*0301 and DRB1*0401 were immunized with 196 influenza H1N1 peptides that contained residues of highly conserved proteome sequences of the human H1N1, H3N2, H1N2, H5N1, and avian influenza A strains. Fifty-four (54) peptides that elicited 63 HLA-restricted peptide-specific T cell epitope responses were identified by IFN-γ ELISpot assay. The 54 peptides were compared to the 2007–2009 human H1N1 sequences for selection of sequences in the design of a new candidate H1N1 vaccine, specifically targeted to highly-conserved HLA-restricted T cell epitopes. Conclusions/Significance Seventeen (17) T cell epitopes in PB1, PB2, and M1 were selected as vaccine targets based on sequence conservation over the past 30 years, high functional avidity, non-identity to human peptides, clustered localization, and promiscuity to multiple HLA alleles. These candidate vaccine antigen sequences may be applicable to any avian or human influenza A virus. PMID:20090904

  7. 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.

  8. Control of a Reassortant Pandemic 2009 H1N1 Influenza Virus Outbreak in an Intensive Swine Breeding Farm: Effect of Vaccination and Enhanced Farm Management Practices.

    PubMed

    Mughini-Gras, Lapo; Beato, Maria Serena; Angeloni, Giorgia; Monne, Isabella; Buniolo, Filippo; Zuliani, Federica; Morini, Matteo; Castellan, Alberto; Bonfanti, Lebana; Marangon, Stefano

    2015-04-13

    Influenza A viruses in swine cause considerable economic losses and raise concerns about their zoonotic potential. The current paucity of thorough empirical assessments of influenza A virus infection levels in swine herds under different control interventions hinders our understanding of their effectiveness. Between 2012 and 2013, recurrent outbreaks of respiratory disease caused by a reassortant pandemic 2009 H1N1 (H1N1pdm) virus were registered in a swine breeding farm in North-East Italy, providing the opportunity to assess an outbreak response plan based on vaccination and enhanced farm management. All sows/gilts were vaccinated with a H1N1pdm-specific vaccine, biosecurity was enhanced, weaning cycles were lengthened, and cross-fostering of piglets was banned. All tested piglets had maternally-derived antibodies at 30 days of age and were detectable in 5.3% of ~90 day-old piglets. There was a significant reduction in H1N1pdm RT-PCR detections after the intervention. Although our study could not fully determine the extent to which the observed trends in seropositivity or RT-PCR positivity among piglets were due to the intervention or to the natural course of the disease in the herd, we provided suggestive evidence that the applied measures were useful in controlling the outbreak, even without an all-in/all-out system, while keeping farm productivity at full.

  9. Control of a Reassortant Pandemic 2009 H1N1 Influenza Virus Outbreak in an Intensive Swine Breeding Farm: Effect of Vaccination and Enhanced Farm Management Practices

    PubMed Central

    Mughini-Gras, Lapo; Beato, Maria Serena; Angeloni, Giorgia; Monne, Isabella; Buniolo, Filippo; Zuliani, Federica; Morini, Matteo; Castellan, Alberto; Bonfanti, Lebana; Marangon, Stefano

    2015-01-01

    Influenza A viruses in swine cause considerable economic losses and raise concerns about their zoonotic potential. The current paucity of thorough empirical assessments of influenza A virus infection levels in swine herds under different control interventions hinders our understanding of their effectiveness. Between 2012 and 2013, recurrent outbreaks of respiratory disease caused by a reassortant pandemic 2009 H1N1 (H1N1pdm) virus were registered in a swine breeding farm in North-East Italy, providing the opportunity to assess an outbreak response plan based on vaccination and enhanced farm management. All sows/gilts were vaccinated with a H1N1pdm-specific vaccine, biosecurity was enhanced, weaning cycles were lengthened, and cross-fostering of piglets was banned. All tested piglets had maternally-derived antibodies at 30 days of age and were detectable in 5.3% of ~90 day-old piglets. There was a significant reduction in H1N1pdm RT-PCR detections after the intervention. Although our study could not fully determine the extent to which the observed trends in seropositivity or RT-PCR positivity among piglets were due to the intervention or to the natural course of the disease in the herd, we provided suggestive evidence that the applied measures were useful in controlling the outbreak, even without an all-in/all-out system, while keeping farm productivity at full. PMID:25932349

  10. Recombinant equine herpesvirus 1 (EHV-1) vaccine protects pigs against challenge with influenza A(H1N1)pmd09.

    PubMed

    Said, Abdelrahman; Lange, Elke; Beer, Martin; Damiani, Armando; Osterrieder, Nikolaus

    2013-05-01

    Swine influenza virus (SIV) is not only an important respiratory pathogen in pigs but also a threat to human health. The pandemic influenza A(H1N1)pdm09 virus likely originated in swine through reassortment between a North American triple reassortant and Eurasian avian-like SIV. The North American triple reassortant virus harbors genes from avian, human and swine influenza viruses. An effective vaccine may protect the pork industry from economic losses and curb the development of new virus variants that may threaten public health. In the present study, we evaluated the efficacy of a recombinant equine herpesvirus type 1 (EHV-1) vaccine (rH_H1) expressing the hemagglutinin H1 of A(H1N1)pdm09 in the natural host. Our data shows that the engineered rH_H1 vaccine induces influenza virus-specific antibody responses in pigs and is able to protect at least partially against challenge infection: no clinical signs of disease were detected and virus replication was reduced as evidenced by decreased nasal virus shedding and faster virus clearance. Taken together, our results indicate that recombinant EHV-1 encoding H1 of A(H1N1)pdm09 may be a promising alternative for protection of pigs against infection with A(H1N1)pdm09 or other influenza viruses.

  11. The reporting completeness of a passive safety surveillance system for pandemic (H1N1) 2009 vaccines: a capture-recapture analysis.

    PubMed

    Huang, Wan-Ting; Huang, Wei-I; Huang, Yu-Wen; Hsu, Chien-Wen; Chuang, Jen-Hsiang

    2012-03-09

    Adverse events following pandemic (H1N1) 2009 vaccines ("2009 H1N1 vaccines") in Taiwan were passively reported to the National Adverse Drug Reaction Reporting System. To evaluate the completeness of spontaneous reporting, cases of death, Guillain-Barré syndrome (GBS), convulsion, Bell's palsy, and idiopathic thrombocytopenic purpura (ITP) after 2009 H1N1 vaccination that occurred between November 1, 2009 and August 31, 2010 were selected from the National Adverse Drug Reaction Reporting System (NADRRS) database and an additionally constructed nationwide large-linked database (LLDB), and matched on a unique personal identifier, date of vaccination (within ±7 days), and date of diagnosis (within ±7 days). Overall, matches occurred between the two data sources included 21 for death, 5 for GBS, 19 for convulsion, 22 for Bell's palsy, and 5 for ITP. The Chapman capture-recapture estimated spontaneous reporting completeness within 0-42 days of vaccination was 4% for death, 71% for GBS, 3% for convulsion, 9% for Bell's palsy, and 15% for ITP. For the interval ≥43 days after vaccination, reporting completeness was 0.1% for death, 14% for GBS, 0.1% for convulsion, <0.1% for Bell's palsy, and 0% for ITP. The estimated-to-expected ratio for Bell's palsy in the interval 0-42 days after vaccination was 1.48 (95% CI 1.11-1.98). Reporting completeness was higher for GBS than other adverse events after 2009 H1N1 vaccination. Linking the NADRRS to existing data sources in a capture-recapture analysis can be considered as an alternative to enhance Taiwan's postlicensure safety assessment of other routine vaccines. Nevertheless, the possibility of an increased risk for Bell's palsy detected by capture-recapture analyses needs further evaluation by controlled studies.

  12. [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

    OBJETIVOS: Valorar y comparar los efectos indeseados de la vacuna de la gripe estacional (VGE) y vacuna de la gripe A H1N1 (VGA) en trabajadores sanitarios. MÉTODOS: Estudio transversal multicéntrico en trabajadores sanitarios de hospitales de agudos, centros de asistencia primaria, centros sociosanitarios, centros de salud mental y un hospital geriátrico participantes en la campaña de vacunación antigripal del 2009. Se enviaron encuestas autocumplimentadas a todos los vacunados con VGE y/o VGA. RESULTADOS: De los 1123 vacunados con VGE se obtienen 527 encuestas válidas (46,9%) y de 461 vacunados con VGA se obtienen 242 encuestas (52,5%). De los trabajadores participantes 527 estaban vacunados sólo con VGE, 117 vacunados previamente con VGE y después VGA (VGE+VGA) y 125 sólo vacunados sólo con VGA. El 18,4% (IC 95% 15,1-21,7) del grupo VGE presentaron algún efecto adverso a la vacuna VGE; en el grupo VGE+VGA el 45,3% (IC 95% 36,3-54,3) presentó una reacción adversa al recibir la VGA, y en el grupo VGA fue el 46,4% (IC 95% 37,7-55,1). En todos los participantes el problema más frecuente fue una reacción local. Las mujeres presentan mayor reacción a VGA y VGE que los hombres. Para todas las edades la VGE es menos reactógena que VGA y que la combinación de ambas vacunas, con la excepción de los trabajadores menores de 29 años. CONCLUSIONES: La VGA es más reactógena que la VGE, sin diferencias por orden de administración. Se observan variaciones por sexo y edad, pero siempre con mayor reactogenicidad para la VGA.

  13. 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.

  14. Seroprotection of HIV-infected subjects after influenza A(H1N1) vaccination is directly associated with baseline frequency of naive T cells.

    PubMed

    Ramirez, Lorenzo A; Daniel, Alexander; Frank, Ian; Tebas, Pablo; Boyer, Jean D

    2014-08-15

    Human immunodeficiency virus type 1 (HIV-1)-infected individuals, despite receipt of antiretroviral therapy (ART), often have impaired vaccine responses. We examined the role that immune activation and cellular phenotypes play in influenza A(H1N1) vaccine responsiveness in HIV-infected subjects receiving ART. Subjects received the H1N1 vaccine (15-µg dose; Novartis), and antibody titers at baseline and after immunization were evaluated. Subjects were classified as responders if, by week 3, seroprotection guidelines were met. Responders had higher percentages of baseline naive T cells and lower percentages of terminally differentiated T cells, compared with nonresponders. Additionally, the naive CD4(+) T-cell percentage and age were negatively correlated. Preservation of naive T-cell populations by starting therapy early could impact vaccine responses against influenza virus and other pathogens, especially as this population ages.

  15. Seroprotection of HIV-Infected Subjects After Influenza A(H1N1) Vaccination Is Directly Associated With Baseline Frequency of Naive T Cells

    PubMed Central

    Ramirez, Lorenzo A.; Daniel, Alexander; Frank, Ian; Tebas, Pablo; Boyer, Jean D.

    2014-01-01

    Human immunodeficiency virus type 1 (HIV-1)–infected individuals, despite receipt of antiretroviral therapy (ART), often have impaired vaccine responses. We examined the role that immune activation and cellular phenotypes play in influenza A(H1N1) vaccine responsiveness in HIV-infected subjects receiving ART. Subjects received the H1N1 vaccine (15-µg dose; Novartis), and antibody titers at baseline and after immunization were evaluated. Subjects were classified as responders if, by week 3, seroprotection guidelines were met. Responders had higher percentages of baseline naive T cells and lower percentages of terminally differentiated T cells, compared with nonresponders. Additionally, the naive CD4+ T-cell percentage and age were negatively correlated. Preservation of naive T-cell populations by starting therapy early could impact vaccine responses against influenza virus and other pathogens, especially as this population ages. PMID:24610877

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

    PubMed

    Valero-Pacheco, Nuriban; Pérez-Toledo, Marisol; 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.

  17. 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

  18. Immunogenicity Associated with the Routine Use of an Influenza A H1N1 Vaccine in Health Care Personnel in Guangzhou, China▿

    PubMed Central

    Di, Biao; Xu, Xinhong; Li, Tiegang; Lu, Enjie; Wu, Jibin; Liu, Yanhui; Chen, Yiyun; Pickerill, Sam; Wang, Ming

    2010-01-01

    We present immunogenicity data on the routine vaccination of 103 health care personnel during the 2009 H1N1 national vaccination campaign. The seroprotection rate (percentage of samples with hemagglutination inhibition titers of ≥1:40) was 83.2% at 30 days postvaccination, lower than those obtained in previously published controlled trials. Low baseline antibody levels and an increase in seroprotection in a negative-control cohort suggest that the virus remains prevalent. PMID:20631339

  19. Randomized Controlled Ferret Study to Assess the Direct Impact of 2008–09 Trivalent Inactivated Influenza Vaccine on A(H1N1)pdm09 Disease Risk

    PubMed Central

    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

  20. 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

  1. 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

  2. The impact of the 2009 influenza A(H1N1) pandemic on attitudes of healthcare workers toward seasonal influenza vaccination 2010/11.

    PubMed

    Brandt, C; Rabenau, H F; Bornmann, S; Gottschalk, R; Wicker, S

    2011-04-28

    The emergence of the influenza A(H1N1)2009 virus provided a major challenge to health services around the world. However, vaccination rates for the public and for healthcare workers (HCWs) have remained low. We performed a study to review the reasons put forward by HCWs to refuse immunisation with the pandemic vaccine in 2009/10 and characterise attitudes in the influenza season 2010/11 due to the emergence of influenza A(H1N1)2009. A survey among HCWs and medical students in the clinical phase of their studies was conducted, using an anonymous questionnaire, at a German university hospital during an influenza vaccination campaign. 1,366 of 3,900 HCWs (35.0%) were vaccinated in the 2010/11 influenza season. Of the vaccinated HCWs, 1,323 (96.9%) completed the questionnaire in addition to 322 vaccinated medical students. Of the 1,645 vaccinees who completed the questionnaire, 712 had not been vaccinated against the influenza A(H1N1)2009 virus in the 2009/10 season. The main reason put forward was the objection to the AS03 adjuvants (239/712, 33.6%). Of the HCWs and students surveyed, 270 of 1,645 (16.4%) stated that the pandemic had influenced their attitude towards vaccination in general. Many German HCWs remained unconvinced of the safety of the pandemic (adjuvanted) influenza vaccine. For this reason, effective risk communication should focus on educating the public and HCWs about influenza vaccine safety and the benefits of vaccination.

  3. The Pandemic Influenza A (H1N1) 2009 Vaccine Does Not Increase the Mortality Rate of Idiopathic Interstitial Pneumonia: A Matched Case-Control Study

    PubMed Central

    Yokomichi, Hiroshi; Kurihara, Shintaro; Yokoyama, Tetsuji; Inoue, Eisuke; Tanaka-Taya, Keiko; Kono, Shigeru; Yamagata, Zentaro

    2014-01-01

    Background Evidence regarding the mortality rate after administration of the pandemic influenza A (H1N1) 2009 vaccine on patients with underlying diseases is currently scarce. We conducted a case-control study in Japan to compare the mortality rates of patients with idiopathic interstitial pneumonia after the vaccines were administered and were not administered. Methods Between October 2009 and March 2010, we collected clinical records in Japan and conducted a 1∶1 matched case-control study. Patients with idiopathic interstitial pneumonia who died during this period were considered case patients, and those who survived were considered control patients. We determined and compared the proportion of each group that received the pandemic influenza A (H1N1) 2009 vaccine and estimated the odds ratio. Finally, we conducted simulations that compensated for the shortcomings of the study associated with adjusted severity of idiopathic interstitial pneumonia. Results The case and control groups each comprised of 75 patients with idiopathic interstitial pneumonia. The proportion of patients who received the pandemic influenza A (H1N1) 2009 vaccine was 30.7% and 38.7% for the case and control groups, respectively. During that winter, the crude conditional odds ratio of mortality was 0.63 (95% confidence interval, 0.25–1.47) and the adjusted conditional odds ratio was 1.18 (95% confidence interval, 0.33–4.49); neither was significant. The simulation study showed more accurate conditional odds ratios of 0.63–0.71. Conclusions In our study, we detected no evidence that the influenza A (H1N1) 2009 vaccine increased the mortality rate of patients with idiopathic interstitial pneumonia. The results, however, are limited by the small sample size and low statistical power. A larger-scale study is required. PMID:24586445

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

    SciTech Connect

    Hu, Weibin; Chen, Aizhong; Miao, Yi; Xia, Shengli; Ling, Zhiyang; Xu, Ke; Wang, Tongyan; Xu, Ying; Cui, Jun; Wu, Hongqiang; Hu, Guiyu; Tian, Lin; Wang, Lingling; Shu, Yuelong; Ma, Xiaowei; Xu, Bianli; Zhang, Jin; Lin, Xiaojun; Bian, Chao; Sun, Bing

    2013-01-20

    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 primarily 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.

  5. Psychogenic illness following vaccination: exploratory study of mass vaccination against pandemic influenza A (H1N1) in 2009 in South Korea

    PubMed Central

    2017-01-01

    Purpose Adverse events during mass vaccination campaigns have had a profoundly negative impact on vaccine coverage rates. The objective of the study was to identify the characteristics of reported psychogenic illness cases following mass vaccination that needed further interventions of the national immunization program. Materials and Methods We collected documents that were submitted to the Korea Centers for Disease Control and Prevention for vaccine injury compensation, and analyzed cases of psychogenic illness following pandemic influenza A (H1N1) vaccination in 2009 which were confirmed by the Korean Advisory Committee on Vaccine Injury Compensation. Results During the 2009-2010 influenza season, 13 million Koreans were vaccinated against pandemic influenza. Of 28 reported psychogenic illness cases following immunization, 25 were vaccinated through school-located mass immunization. Significant numbers of them were female adolescents (68%) or had underlying vulnerable conditions or emotional life stressors (36%). They required lengthy hospitalization (median, 7 days) and high medical costs (median, US $1,582 per case). Conclusion Health authorities and organizers of future mass vaccinations should be well aware of the possible occurrence of psychogenic illness, acknowledge their detailed characteristics, and take its economic burden into account to mitigate the risk of transmission of infectious diseases efficiently. PMID:28168171

  6. A/H1N1 antibodies and TRIB2 autoantibodies in narcolepsy patients diagnosed in conjunction with the Pandemrix vaccination campaign in Sweden 2009-2010.

    PubMed

    Lind, Alexander; Ramelius, Anita; Olsson, Tomas; Arnheim-Dahlström, Lisen; Lamb, Favelle; Khademi, Mohsen; Ambati, Aditya; Maeurer, Markus; Nilsson, Anna-Lena; Bomfim, Izaura Lima; Fink, Katharina; Lernmark, Åke

    2014-05-01

    Narcolepsy is a lifelong sleep disorder related to hypocretin deficiency resulting from a specific loss of hypocretin-producing neurons in the lateral hypothalamic area. The disease is thought to be autoimmune due to a strong association with HLA-DQB1*06:02. In 2009 the World Health Organization (WHO) declared the H1N1 2009 flu pandemic (A/H1N1PDM09). In response to this, the Swedish vaccination campaign began in October of the same year, using the influenza vaccine Pandemrix(®). A few months later an excess of narcolepsy cases was observed. It is still unclear to what extent the vaccination campaign affected humoral autoimmunity associated with narcolepsy. We studied 47 patients with narcolepsy (6-69 years of age) and 80 healthy controls (3-61 years of age) selected after the Pandemrix vaccination campaign. The first aim was to determine antibodies against A/H1N1 and autoantibodies to Tribbles homolog 2 (TRIB2), a narcolepsy autoantigen candidate as well as to GAD65 and IA-2 as disease specificity controls. The second aim was to test if levels and frequencies of these antibodies and autoantibodies were associated with HLA-DQB1*06:02. In vitro transcribed and translated [(35)S]-methionine and -cysteine-labeled influenza A virus (A/California/04/2009/(H1N1)) segment 4 hemagglutinin was used to detect antibodies in a radiobinding assay. Autoantibodies to TRIB2, GAD65 and IA-2 were similarly detected in standard radiobinding assays. The narcolepsy patients had higher median levels of A/H1N1 antibodies than the controls (p = 0.006). A/H1N1 antibody levels were higher among the <13 years old (n = 12) compared to patients who were older than 30 years (n = 12, p = 0.014). Being HLA-DQB1*06:02 positive was associated with higher A/H1N1 antibody levels in both patients and controls (p = 0.026). Serum autoantibody levels to TRIB2 were low overall and high binders did not differ between patients and controls. We observed an association between levels of A/H1N1

  7. Highly Predictive Model for a Protective Immune Response to the A(H1N1)pdm2009 Influenza Strain after Seasonal Vaccination.

    PubMed

    Jürchott, Karsten; Schulz, Axel Ronald; Bozzetti, Cecilia; Pohlmann, Dominika; Stervbo, Ulrik; Warth, Sarah; Mälzer, Julia Nora; Waldner, Julian; Schweiger, Brunhilde; Olek, Sven; Grützkau, Andreas; Babel, Nina; Thiel, Andreas; Neumann, Avidan Uriel

    2016-01-01

    Understanding the immune response after vaccination against new influenza strains is highly important in case of an imminent influenza pandemic and for optimization of seasonal vaccination strategies in high risk population groups, especially the elderly. Models predicting the best sero-conversion response among the three strains in the seasonal vaccine were recently suggested. However, these models use a large number of variables and/or information post- vaccination. Here in an exploratory pilot study, we analyzed the baseline immune status in young (<31 years, N = 17) versus elderly (≥50 years, N = 20) donors sero-negative to the newly emerged A(H1N1)pdm09 influenza virus strain and correlated it with the serological response to that specific strain after seasonal influenza vaccination. Extensive multi-chromatic FACS analysis (36 lymphocyte sub-populations measured) was used to quantitatively assess the cellular immune status before vaccination. We identified CD4+ T cells, and amongst them particularly naive CD4+ T cells, as the best correlates for a successful A(H1N1)pdm09 immune response. Moreover, the number of influenza strains a donor was sero-negative to at baseline (NSSN) in addition to age, as expected, were important predictive factors. Age, NSSN and CD4+ T cell count at baseline together predicted sero-protection (HAI≥40) to A(H1N1)pdm09 with a high accuracy of 89% (p-value = 0.00002). An additional validation study (N = 43 vaccinees sero-negative to A(H1N1)pdm09) has confirmed the predictive value of age, NSSN and baseline CD4+ counts (accuracy = 85%, p-value = 0.0000004). Furthermore, the inclusion of donors at ages 31-50 had shown that the age predictive function is not linear with age but rather a sigmoid with a midpoint at about 50 years. Using these results we suggest a clinically relevant prediction model that gives the probability for non-protection to A(H1N1)pdm09 influenza strain after seasonal multi-valent vaccination as a continuous

  8. Why were Turks unwilling to accept the A/H1N1 influenza-pandemic vaccination? People's beliefs and perceptions about the swine flu outbreak and vaccine in the later stage of the epidemic.

    PubMed

    Gaygısız, Ümmügülsüm; Gaygısız, Esma; Özkan, Türker; Lajunen, Timo

    2010-12-16

    This study investigated the acceptability of the A/H1N1 influenza vaccination and related factors among 1137 adults in the later stage of the A/H1N1 outbreak in Turkey. Having already been vaccinated or intending to get vaccinated were related to trust in the vaccine effectiveness, perceived risk of the side effects, and benefits of getting vaccinated. Perceived long term consequences of the A/H1N1 infection, perceptions of the A/H1N1 information in media, and barriers for getting vaccinated were related to intention whereas anticipated epidemic situation in Turkey, being chronically ill, and being not married were related to having already been vaccinated.

  9. Efficacy of vaccination with different combinations of MF59-adjuvanted and nonadjuvanted seasonal and pandemic influenza vaccines against pandemic H1N1 (2009) influenza virus infection in ferrets.

    PubMed

    van den Brand, Judith M A; Kreijtz, Joost H C M; Bodewes, Rogier; Stittelaar, Koert J; van Amerongen, Geert; Kuiken, Thijs; Simon, James; Fouchier, Ron A M; Del Giudice, Giuseppe; Rappuoli, Rino; Rimmelzwaan, Guus F; Osterhaus, Albert D M E

    2011-03-01

    Serum antibodies induced by seasonal influenza or seasonal influenza vaccination exhibit limited or no cross-reactivity against the 2009 pandemic swine-origin influenza virus of the H1N1 subtype (pH1N1). Ferrets immunized once or twice with MF59-adjuvanted seasonal influenza vaccine exhibited significantly reduced lung virus titers but no substantial clinical protection against pH1N1-associated disease. However, priming with MF59-adjuvanted seasonal influenza vaccine significantly increased the efficacy of a pandemic MF59-adjuvanted influenza vaccine against pH1N1 challenge. Elucidating the mechanism involved in this priming principle will contribute to our understanding of vaccine- and infection-induced correlates of protection. Furthermore, a practical consequence of these findings is that during an emerging pandemic, the implementation of a priming strategy with an available adjuvanted seasonal vaccine to precede the eventual pandemic vaccination campaign may be useful and life-saving.

  10. Association between monovalent influenza A (H1N1) pdm09 vaccine and pneumonia among the elderly in the 2009-2010 season in Japan: A case-control study.

    PubMed

    Kondo, Kyoko; Suzuki, Kanzo; Washio, Masakazu; Ohfuji, Satoko; Fukushima, Wakaba; Maeda, Akiko; Hirota, Yoshio

    2015-01-01

    We investigated the association between monovalent influenza A (H1N1) pdm09 (H1N1pdm) vaccine and pneumonia in elderly people. Study design was a hospital-based, matched case-control study. Cases comprised patients ≥ 65 years old who had been newly diagnosed with pneumonia. For each case, 2 controls were defined as individuals with other diseases (not pneumonia) who were matched by sex, age, entry date, and the visited hospital. Study period was the interval from 1 September 2009 until 30 September 2010. Because a pandemic of influenza A (H1N1) occurred during study period, we analyzed selected subjects who had enrolled during the influenza A (H1N1) pandemic. We calculated the odds ratios (ORs) and 95% confidence intervals (CIs) for pneumonia in H1N1pdm-vaccinated subjects compared with unvaccinated subjects using a conditional logistic regression model to assess the association between H1N1pdm vaccine and pneumonia. The subjects during the period of the influenza A (H1N1) pandemic were 20 cases and 40 controls. Subjects who had received H1N1pdm vaccine showed a significantly decreased OR for pneumonia (OR = 0.10, 95% CI = 0.01-0.98) compared with unvaccinated subjects. In conclusion, H1N1pdm vaccination may have prevented pneumonia among the elderly during the 2009-2010 influenza A (H1N1) pandemic in Japan.

  11. Immunogenicity, boostability, and sustainability of the immune response after vaccination against Influenza A virus (H1N1) 2009 in a healthy population.

    PubMed

    Huijskens, Elisabeth; Rossen, John; Mulder, Paul; van Beek, Ruud; van Vugt, Hennie; Verbakel, Johannes; Rimmelzwaan, Guus; Koopmans, Marion; Peeters, Marcel

    2011-09-01

    The emergence of a new influenza A virus (H1N1) variant in 2009 led to a worldwide vaccination program, which was prepared in a relatively short period of time. This study investigated the humoral immunity against this virus before and after vaccination with a 2009 influenza A virus (H1N1) monovalent MF59-adjuvanted vaccine, as well as the persistence of vaccine-induced antibodies. Our prospective longitudinal study included 498 health care workers (mean age, 43 years; median age, 44 years). Most (89%) had never or only occasionally received a seasonal influenza virus vaccine, and 11% were vaccinated annually (on average, for >10 years). Antibody titers were determined by a hemagglutination inhibition (HI) assay at baseline, 3 weeks after the first vaccination, and 5 weeks and 7 months after the second vaccination. Four hundred thirty-five persons received two doses of the 2009 vaccine. After the first dose, 79.5% developed a HI titer of ≥40. This percentage increased to 83.3% after the second dose. Persistent antibodies were found in 71.9% of the group that had not received annual vaccinations and in 43.8% of the group that had received annual vaccinations. The latter group tended to have lower HI titers (P=0.09). With increasing age, HI titers decreased significantly, by 2.4% per year. A single dose of the 2009 vaccine was immunogenic in almost 80% of the study population, whereas an additional dose resulted in significantly increased titers only in persons over 50. Finally, a reduced HI antibody response against the 2009 vaccine was found in adults who had previously received seasonal influenza virus vaccination. More studies on the effect of yearly seasonal influenza virus vaccination on the immune response are warranted.

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

    PubMed Central

    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. PMID:27093541

  13. HA1-2-fljB Vaccine Induces Immune Responses against Pandemic Swine-Origin H1N1 Influenza Virus in Mice.

    PubMed

    Kang, Xilong; Yang, Yun; Jiao, Yang; Song, Hongqin; Song, Li; Xiong, Dan; Wu, Lili; Pan, Zhiming; Jiao, Xinan

    2016-01-01

    In 2009, a novel pandemic swine-origin influenza A (H1N1) virus caused a public emergency of international concern. Vaccination is the primary strategy for the control of influenza epidemics. However, the poor immunopotency of many vaccine antigens is a major barrier to the development of effective vaccines against influenza. Flagellin, a Toll-like receptor 5 (TLR5) ligand, has been used as an adjuvant to enhance the immunopotency of vaccines in preclinical studies. Here, we developed a recombinant candidate vaccine, HA1-2-fljB, in which the globular head of the hemagglutinin (HA) antigen (residues 62-284) from H1N1 virus was fused genetically to the N-terminus of Salmonella typhimurium fljB. The recombinant HA1-2-fljB protein was expressed efficiently in Escherichia coli, and the immunogenicity and protective efficacy of recombinant HA1-2-fljB were evaluated in a mouse model. Immunization with HA1-2-fljB elicited robust IgG antibodies and neutralizing antibodies and completely protected the mice against infection by swine-origin influenza A/swine/Jangsu/38/2010 (H1N1). These results suggest that HA antigen placed at the N-terminus of flagellin is also an excellent starting point for creating a fusion HA1-2-fljB protein as a candidate vaccine, and the recombinant HA1-2-fljB protein will contribute to the development of a more effective vaccine against swine-origin influenza virus infection.

  14. Comparison of Pandemrix and Arepanrix, two pH1N1 AS03-adjuvanted vaccines differentially associated with narcolepsy development.

    PubMed

    Jacob, Louis; Leib, Ryan; Ollila, Hanna M; Bonvalet, Mélodie; Adams, Christopher M; Mignot, Emmanuel

    2015-07-01

    Narcolepsy onset in children has been associated with the 2009 influenza A H1N1 pandemic and vaccination with Pandemrix. However it was not clearly observed with other adjuvanted pH1N1 vaccines such as Arepanrix or Focetria. Our aim was to characterize the differences between Pandemrix and Arepanrix that might explain the risk for narcolepsy after Pandemrix vaccination using 2D-DIGE and mass spectrometry (MS). We found that Pandemrix (2009 batch) and Arepanrix (2010 batch) showed 5 main viral proteins: hemagglutinin HA1 and HA2 subunits, neuraminidase NA, nucleoprotein NP, and matrix protein MA1 and non-viral proteins from the Gallus gallus growth matrix used in the manufacturing of the vaccines. Latticed patterns of HA1, HA2 and NA indicated charge and molecular weight heterogeneity, a phenomenon likely caused by glycosylation and sulfation. Overall, Pandemrix contained more NP and NA, while Arepanrix displayed a larger diversity of viral and chicken proteins, with the exception of five chicken proteins (PDCD6IP, TSPAN8, H-FABP, HSP and TUB proteins) that were relatively more abundant in Pandemrix. Glycosylation patterns were similar in both vaccines. A higher degree of deamidation and dioxidation was found in Pandemrix, probably reflecting differential degradation across batches. Interestingly, HA1 146N (residue 129N in the mature protein) displayed a 10-fold higher deamidation in Arepanrix versus Pandemrix. In recent vaccine strains and Focetria, 146N is mutated to D which is associated with increased production yields suggesting that 146N deamidation may have also occurred during the manufacturing of Arepanrix. The presence of 146N in large relative amounts in Pandemrix and the wild type virus and in lower relative quantities in Arepanrix or other H1N1 vaccines may have affected predisposition to narcolepsy.

  15. 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.

  16. The social ecological model as a framework for determinants of 2009 H1N1 influenza vaccine uptake in the United States.

    PubMed

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

    2012-04-01

    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 January 2010 with significant oversamples of Blacks and Hispanics, this study found that 18.4% (95% confidence interval = 15.6-21.5) had gotten the 2009 H1N1 vaccine. Variables at each level of the social ecological model were significant predictors of uptake as well as of intent to get the vaccine. The intrapersonal level explained 53%, the interpersonal explained 47%, the institutional level explained 34%, and the policy and community levels each explained 8% of the variance associated with vaccine uptake. The levels together explained 65% of the variance, suggesting that interventions targeting multiple levels of the framework would be more effective than interventions aimed at a single level.

  17. Plant-based rapid production of recombinant subunit hemagglutinin vaccines targeting H1N1 and H5N1 influenza.

    PubMed

    Shoji, Yoko; Chichester, Jessica A; Jones, Mark; Manceva, Slobodanka D; Damon, Emily; Mett, Vadim; Musiychuk, Konstantin; Bi, Hong; Farrance, Christine; Shamloul, Moneim; Kushnir, Natasha; Sharma, Satish; Yusibov, Vidadi

    2011-01-01

    In 2009, a novel H1N1 swine influenza virus was isolated from infected humans in Mexico and the United States, and rapidly spread around the world. Another virus, a highly pathogenic avian influenza virus of the H5N1 subtype, identified by the World Health Organization as a potential pandemic threat in 1997, continues to be a significant risk. While vaccination is the preferred strategy for the prevention and control of influenza infections, the traditional egg-based approach to producing influenza vaccines does not provide sufficient capacity and adequate speed to satisfy global needs to combat newly emerging strains, seasonal or potentially pandemic. Significant efforts are underway to develop and implement new cell substrates with improved efficiency for influenza vaccine development and manufacturing. In recent years, plants have been used to produce recombinant proteins including subunit vaccines and antibodies. The main advantages of using plant systems for the production of vaccine antigens against influenza are their independence from pathogenic viruses, and cost and time efficiency. Here, we describe the large-scale production of recombinant hemagglutinin proteins from A/California/04/09 (H1N1) and A/Indonesia/05/05 (H5N1) strains of influenza virus in Nicotiana benthamiana plants, and their immunogenicity (serum hemagglutination inhibition and virus neutralizing antibodies), and safety in animal models. These results support the testing of these candidate vaccines in human volunteers and also the utility of our plant expression system for large-scale recombinant influenza vaccine production.

  18. A polyvalent influenza A DNA vaccine induces heterologous immunity and protects pigs against pandemic A(H1N1)pdm09 virus infection.

    PubMed

    Bragstad, Karoline; Vinner, Lasse; Hansen, Mette Sif; Nielsen, Jens; Fomsgaard, Anders

    2013-04-26

    The composition of current influenza protein vaccines has to be reconsidered every season to match the circulating influenza viruses, continuously changing antigenicity. Thus, influenza vaccines inducing a broad cross-reactive immune response would be a great advantage for protection against both seasonal and emerging influenza viruses. We have developed an alternative influenza vaccine based on DNA expressing selected influenza proteins of pandemic and seasonal origin. In the current study, we investigated the protection of a polyvalent influenza DNA vaccine approach in pigs. We immunised pigs intradermally with a combination of influenza DNA vaccine components based on the pandemic 1918 H1N1 (M and NP genes), pandemic 2009 H1N1pdm09 (HA and NA genes) and seasonal 2005 H3N2 genes (HA and NA genes) and investigated the protection against infection with virus both homologous and heterologous to the DNA vaccine components. We found that pigs challenged with a virus homologous to the HA and NA DNA vaccine components were well protected from infection. In addition, heterologous challenge virus was cleared rapidly compared to the unvaccinated control pigs. Immunisation by electroporation induced HI antibodies >40 HAU/ml seven days after second vaccination. Heterologous virus challenge as long as ten weeks after last immunisation was able to trigger a vaccine antibody HI response 26 times higher than in the control pigs. The H3N2 DNA vaccine HA and NA genes also triggered an effective vaccine response with protective antibody titres towards heterologous H3N2 virus. The described influenza DNA vaccine is able to induce broadly protective immune responses even in a larger animal, like the pig, against both heterologous and homologous virus challenges despite relatively low HI titres after vaccination. The ability of this DNA vaccine to limit virus shedding may have an impact on virus spread among pigs which could possibly extend to humans as well, thereby diminishing the

  19. The Impact of Immunosenescence on Humoral Immune Response Variation after Influenza A/H1N1 Vaccination in Older Subjects

    PubMed Central

    Haralambieva, Iana H.; Painter, Scott D.; Kennedy, Richard B.; Ovsyannikova, Inna G.; Lambert, Nathaniel D.; Goergen, Krista M.; Oberg, Ann L.; Poland, Gregory A.

    2015-01-01

    Background Although influenza causes significant morbidity and mortality in the elderly, the factors underlying the reduced vaccine immunogenicity and efficacy in this age group are not completely understood. Age and immunosenescence factors, and their impact on humoral immunity after influenza vaccination, are of growing interest for the development of better vaccines for the elderly. Methods We assessed associations between age and immunosenescence markers (T cell receptor rearrangement excision circles – TREC content, peripheral white blood cell telomerase – TERT expression and CD28 expression on T cells) and influenza A/H1N1 vaccine-induced measures of humoral immunity in 106 older subjects at baseline and three timepoints post-vaccination. Results TERT activity (TERT mRNA expression) was significantly positively correlated with the observed increase in the influenza-specific memory B cell ELISPOT response at Day 28 compared to baseline (p-value=0.025). TREC levels were positively correlated with the baseline and early (Day 3) influenza A/H1N1-specific memory B cell ELISPOT response (p-value=0.042 and p-value=0.035, respectively). The expression and/or expression change of CD28 on CD4+ and/or CD8+ T cells at baseline and Day 3 was positively correlated with the influenza A/H1N1-specific memory B cell ELISPOT response at baseline, Day 28 and Day 75 post-vaccination. In a multivariable analysis, the peak antibody response (HAI and/or VNA at Day 28) was negatively associated with age, the percentage of CD8+CD28low T cells, IgD+CD27- naïve B cells, and percentage overall CD20- B cells and plasmablasts, measured at Day 3 post-vaccination. The early change in influenza-specific memory B cell ELISPOT response was positively correlated with the observed increase in influenza A/H1N1-specific HAI antibodies at Day 28 and Day 75 relative to baseline (p-value=0.007 and p-value=0.005, respectively). Conclusion Our data suggest that influenza-specific humoral immunity

  20. ADHERENCE TO INFLUENZA VACCINATION AMONG MEDICAL STUDENTS DURING AND AFTER INFLUENZA A (H1N1) PANDEMIC

    PubMed Central

    de PAULA, Stéfano Ivani; de PAULA, Gustavo Ivani; CUNEGUNDES, Kelly Simone Almeida; de MORAES-PINTO, Maria Isabel

    2016-01-01

    SUMMARY This study evaluated the adherence to influenza vaccination among medical students in 2010 and 2011. From August to December 2011, a questionnaire was used to record the influenza vaccination in 2010 and 2011, reasons for acceptance of the influenza vaccine and knowledge of healthcare workers about the influenza vaccine recommendation. One hundred and forty-four students from the 2ndto the 6th years of the medical school were interviewed. A great adherence to pandemic influenza vaccine was noted in 2010, (91% of the students), with "self-protection" being the most common reason cited for vaccination. Other determinants for the vaccination during pandemic were "convenient access to vaccine" and "encouragement by peers and teachers in workplaces and at the university". However, there was a great decay in the acceptance to vaccine in the next influenza season (2011). Only 42% of the students received the vaccine. They claimed "lack of time" and "have forgotten to take the vaccine" as the main reasons. The "knowledge on the recommendation of influenza vaccine to healthcare workers" increased when the students come to attend the last year of the medical school, but that was an insufficient motivator for vaccination. Strategies to increase vaccination should be based on the abovementioned aspects for the adoption of effective measures in both, pandemic and seasonal periods. PMID:27828623

  1. ADHERENCE TO INFLUENZA VACCINATION AMONG MEDICAL STUDENTS DURING AND AFTER INFLUENZA A (H1N1) PANDEMIC.

    PubMed

    Paula, Stéfano Ivani de; Paula, Gustavo Ivani de; Cunegundes, Kelly Simone Almeida; Moraes-Pinto, Maria Isabel de

    2016-11-03

    This study evaluated the adherence to influenza vaccination among medical students in 2010 and 2011. From August to December 2011, a questionnaire was used to record the influenza vaccination in 2010 and 2011, reasons for acceptance of the influenza vaccine and knowledge of healthcare workers about the influenza vaccine recommendation. One hundred and forty-four students from the 2ndto the 6th years of the medical school were interviewed. A great adherence to pandemic influenza vaccine was noted in 2010, (91% of the students), with "self-protection" being the most common reason cited for vaccination. Other determinants for the vaccination during pandemic were "convenient access to vaccine" and "encouragement by peers and teachers in workplaces and at the university". However, there was a great decay in the acceptance to vaccine in the next influenza season (2011). Only 42% of the students received the vaccine. They claimed "lack of time" and "have forgotten to take the vaccine" as the main reasons. The "knowledge on the recommendation of influenza vaccine to healthcare workers" increased when the students come to attend the last year of the medical school, but that was an insufficient motivator for vaccination. Strategies to increase vaccination should be based on the abovementioned aspects for the adoption of effective measures in both, pandemic and seasonal periods.

  2. Investigating the effect of AS03 adjuvant on the plasma cell repertoire following pH1N1 influenza vaccination

    PubMed Central

    Galson, J. D.; Trück, J.; Kelly, D. F.; van der Most, R.

    2016-01-01

    Influenza pandemics require rapid deployment of effective vaccines for control. Adjuvants such as AS03 improve vaccine immunogenicity, but this mechanism is poorly understood. We used high-throughput B cell receptor sequencing of plasma cells produced following AS03-adjuvanted and non-adjuvanted 2009 pandemic H1N1 vaccination, as well as pre-pandemic seasonal influenza vaccination to elucidate the effect of the adjuvant on the humoral immune response. By analyzing mutation levels, it was possible to distinguish sequences from cells that were recently activated from naïve B cells from those that were activated by memory recall. We show that the adjuvant functions through two mechanisms. First, the adjuvant stimulates increased activation of naïve B cells, thus reducing immune interference with previous vaccine responses. Second, the adjuvant is able to increase the adaptability of the recalled cells to give improved specificity to the new vaccine antigen. We thus show how AS03 enhances pH1N1 immune responses, and reduces immune interference. PMID:27849037

  3. Healthcare workers under a mandated H1N1 vaccination policy with employment termination penalty: a survey to assess employee perception.

    PubMed

    Winston, Lori; Wagner, Stephanie; Chan, Shu

    2014-08-20

    The ethical debate over mandatory healthcare worker (HCW) influenza vaccination is a heated one. Our study hospital instituted a mandatory employee influenza vaccination policy for the 2009-2010 influenza season during the highly publicized pandemic of the H1N1 "Swine Flu." Under this mandate there was no informed declination option, and termination of employment was the consequence for noncompliance. Our objective was to examine HCW perceptions of the H1N1 influenza virus, the vaccine, and the strict mandated vaccination policy. A survey was designed, distributed, and anonymously collected. In total, 202 completed questionnaires were obtained via accidental sampling by the investigators achieving a 100% response rate. Data analysis showed that 31.7% of surveyed HCWs felt the mandate was an infringement on their rights and 3.5% of HCWs would electively seek employment elsewhere. Significantly more nurses and clerks/technicians were opposed to the mandate compared to other types of employees. 96% felt that the mandating hospital should be liable should a significant adverse effect occur from receiving the vaccine. While the mandate helped to increase HCW influenza vaccination rates dramatically, the strict consequence of employment termination created negative feelings of coercion. Adopting a policy that includes a declination option with mandatory masking during influenza season might be a more widely acceptable and still adequate approach.

  4. Persistence and avidity maturation of antibodies to A(H1N1)pdm09 in healthcare workers following repeated annual vaccinations.

    PubMed

    Eidem, Synnøve; Tete, Sarah M; Jul-Larsen, Åsne; Hoschler, Katja; Montomoli, Emanuele; Brokstad, Karl A; Cox, Rebecca J

    2015-08-07

    Healthcare workers are at increased risk of influenza infection through direct patient care, particularly during the early stages of a pandemic. Although influenza vaccination is widely recommended in Healthcare workers, data on long-term immunogenicity of vaccination in healthcare workers are lacking. The present study was designed to assess the persistence of the humoral response after pandemic vaccination as well as the impact of repeated annual vaccination in healthcare workers (n=24). Pandemic influenza vaccination resulted in a significant increase in haemagglutination inhibition (HI) antibody titers with 93-100% of subjects achieving protective titers 21-days post each of the three annual vaccinations. Seroprotective antibodies measured by HI, microneutralization and single radial hemolysis assays were present in 77-94% of healthcare workers 6 months post-vaccination. Repeated vaccination resulted in an increased duration of seroprotective antibodies with seroprotective titers increasing from 35-62% 12 months after 2009 pandemic vaccination to 50-75% 12 months after 2010 vaccination. Furthermore, repeated annual vaccination augmented the avidity of influenza-specific IgG antibodies. In conclusion, we have shown that A(H1N1)pdm09 vaccination induces high seroprotective titers that persist for at least 6 months. We demonstrate that repeated vaccination is beneficial to healthcare workers and results in further avidity maturation of vaccine-induced antibodies.

  5. 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

  6. The immunogenetics of narcolepsy associated with A(H1N1)pdm09 vaccination (Pandemrix) supports a potent gene-environment interaction.

    PubMed

    Bomfim, I L; Lamb, F; Fink, K; Szakács, A; Silveira, A; Franzén, L; Azhary, V; Maeurer, M; Feltelius, N; Darin, N; Hallböök, T; Arnheim-Dahlström, L; Kockum, I; Olsson, T

    2017-03-23

    The influenza A(H1N1)pdm09 vaccination campaign from 2009 to 2010 was associated with a sudden increase in the incidence of narcolepsy in several countries. Narcolepsy with cataplexy is strongly associated with the human leukocyte antigen (HLA) class II DQB1*06:02 allele, and protective associations with the DQB1*06:03 allele have been reported. Several non-HLA gene loci are also associated, such as common variants of the T-cell receptor-α (TRA), the purinergic receptor P2RY11, cathepsin H (CTSH) and TNFSF4/OX40L/CD252. In this retrospective multicenter study, we investigated if these predisposing gene loci were also involved in vaccination-associated narcolepsy. We compared HLA- along with single-nucleotide polymorphism genotypes for non-HLA regions between 42 Pandemrix-vaccinated narcolepsy cases and 1990 population-based controls. The class II gene loci associations supported previous findings. Nominal association (P-value<0.05) with TRA as well as suggestive (P-value<0.1) associations with P2RY11 and CTSH were found. These associations suggest a very strong gene-environment interaction, in which the influenza A(H1N1)pdm09 strain or Pandemrix vaccine can act as potent environmental triggers.Genes and Immunity advance online publication, 23 March 2017; doi:10.1038/gene.2017.1.

  7. Adverse events with the influenza A(H1N1) vaccine Pandemrix® at healthcare professionals in Portugal.

    PubMed

    Marques, Joana Isabel; Ribeiro Vaz, Inês; Santos, Cristina; Polónia, Jorge

    2013-01-01

    Introdução: Os profissionais de saúde foram um grupo prioritário para vacinação contra a pandemia da Gripe A (H1N1), Pandemrix®. Assim, monitorizar os eventos adversos relacionados com esta vacina neste grupo específico poderá originar informação valiosa relacionada com o perfil de segurança da vacina. O nosso objetivo foi identificar os eventos adversos após imunização com a vacina Pandemrix® em profissionais de saúde. Material e Métodos: Foi desenhado um questionário de monitorização dos eventos adversos ocorridos com a vacina Pandemrix®. O questionário foi distribuído aos profissionais de saúde a trabalhar em três centros hospitalares da região norte do País, vacinados no período de 26 de Outubro de 2009 a 31 de janeiro de 2009. Resultados: Dos 2358 profissionais de saúde que aceitaram participar no estudo, 864 (37%) devolveram o questionário preenchido. Destes, 73% experienciaram pelo menos um evento adverso após imunização, mas só 8% experienciaram um evento inesperado. Os eventos adversos mais frequentemente reportados foram os esperados e muito comuns: reações locais no local de administração (57%), mialgia (31%), fadiga (incluindo astenia) (24%) e dor de cabeça (19%). Não foram reportados casos de eventos de maior gravidade para a saúde, tais como morte ou risco de vida. O género feminino e a existência de doença de base foram fatores de risco independentes para o desenvolvimento de pelo menos um evento adverso após imunização com a Pandemrix®. Conclusões: O nosso trabalho sugere um perfil de segurança aceitável da vacina pandémica Pandermix® em profissionais de saúde. Tanto a frequência como a severidade dos eventos adversos não se verificaram superiores ao esperado.

  8. Perception of the A/H1N1 influenza pandemic and acceptance of influenza vaccination by Université Claude Bernard Lyon 1 staff: A descriptive study.

    PubMed

    Amour, Sélilah; Djhehiche, Khaled; Zamora, Adeline; Bergeret, Alain; Vanhems, Philippe

    2015-01-01

    We assessed the perception and attitudes of university staff, including medical school and other science specialties, toward the 2009 A/H1N1 influenza pandemic and influenza vaccination program. A cross-sectional online survey was conducted among 4,529 university personnel on October 19-20, 2009. Seven hundred (15%) employees participated in the study. Only 18% were willing to be vaccinated, men more than women (29% versus 9%, P < 0.001), and professors/researchers more than administrative/technical staff (30% vs. 6%, P < 0.001). Intention to be vaccinated was insufficient. Additional efforts are needed to improve information dissemination among university staff. Medical university personnel should receive more information to increase vaccine coverage and protect them as well as patients.

  9. Perception of the A/H1N1 influenza pandemic and acceptance of influenza vaccination by Université Claude Bernard Lyon 1 staff: A descriptive study

    PubMed Central

    Amour, Sélilah; Djhehiche, Khaled; Zamora, Adeline; Bergeret, Alain; Vanhems, Philippe

    2015-01-01

    We assessed the perception and attitudes of university staff, including medical school and other science specialties, toward the 2009 A/H1N1 influenza pandemic and influenza vaccination program. A cross-sectional online survey was conducted among 4,529 university personnel on October 19–20, 2009. Seven hundred (15%) employees participated in the study. Only 18% were willing to be vaccinated, men more than women (29% versus 9%, P < 0.001), and professors/researchers more than administrative/technical staff (30% vs. 6%, P < 0.001). Intention to be vaccinated was insufficient. Additional efforts are needed to improve information dissemination among university staff. Medical university personnel should receive more information to increase vaccine coverage and protect them as well as patients. PMID:25715115

  10. 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

  11. Cost comparison of 2 mass vaccination campaigns against influenza A H1N1 in New York City.

    PubMed

    Kansagra, Susan M; McGinty, Meghan D; Morgenthau, Beth Maldin; Marquez, Monica L; Rosselli-Fraschilla, Annmarie; Zucker, Jane R; Farley, Thomas A

    2012-07-01

    Objectives. We estimated and compared total costs and costs per dose administered for 2 influenza A 2009 monovalent vaccine campaigns in New York City: an elementary school-located campaign targeting enrolled children aged 4 years and older, and a community-based points-of-dispensing campaign for anyone aged 4 years and older. Methods. We determined costs from invoices or we estimated costs. We obtained vaccination data from the Citywide Immunization Registry and reports from the community points of dispensing. Results. The school campaign delivered approximately 202,089 vaccines for $17.9 million and $88 per dose. The community campaign delivered 49,986 vaccines for $7.6 million and $151 per dose. At projected capacity, the school campaign could have delivered 371,827 doses at $53 each or $13 each when we excluded the value of in-kind resources. The community points of dispensing could have administered 174,000 doses at $51 each or $24 each when we excluded the value of in-kind resources. Conclusions. The school campaign delivered vaccines at a lower cost per dose than did the community campaign. Had demand been higher, both campaigns may have delivered vaccine at lower, more comparable cost per dose.

  12. Cost Comparison of 2 Mass Vaccination Campaigns Against Influenza A H1N1 in New York City

    PubMed Central

    Kansagra, Susan M.; McGinty, Meghan D.; Morgenthau, Beth Maldin; Marquez, Monica L.; Rosselli-Fraschilla, Annmarie; Zucker, Jane R.; Farley, Thomas A.

    2012-01-01

    Objectives. We estimated and compared total costs and costs per dose administered for 2 influenza A 2009 monovalent vaccine campaigns in New York City: an elementary school–located campaign targeting enrolled children aged 4 years and older, and a community-based points-of-dispensing campaign for anyone aged 4 years and older. Methods. We determined costs from invoices or we estimated costs. We obtained vaccination data from the Citywide Immunization Registry and reports from the community points of dispensing. Results. The school campaign delivered approximately 202 089 vaccines for $17.9 million and $88 per dose. The community campaign delivered 49 986 vaccines for $7.6 million and $151 per dose. At projected capacity, the school campaign could have delivered 371 827 doses at $53 each or $13 each when we excluded the value of in-kind resources. The community points of dispensing could have administered 174 000 doses at $51 each or $24 each when we excluded the value of in-kind resources. Conclusions. The school campaign delivered vaccines at a lower cost per dose than did the community campaign. Had demand been higher, both campaigns may have delivered vaccine at lower, more comparable cost per dose. PMID:22676501

  13. Psychiatric Comorbidity and Cognitive Profile in Children with Narcolepsy with or without Association to the H1N1 Influenza Vaccination

    PubMed Central

    Szakács, Attila; Hallböök, Tove; Tideman, Pontus; Darin, Niklas; Wentz, Elisabet

    2015-01-01

    Objectives: To evaluate psychiatric comorbidity and the cognitive profile in children and adolescents with narcolepsy in western Sweden and the relationship of these problems to H1N1 vaccination. Patients: Thirty-eight patients were included in the study. Design: We performed a population-based, cross-sectional study to investigate psychiatric comorbidity using a test battery of semistructured interviews generating Diagnostic and Statistical Manual of Mental Disorders, 4th Edition diagnoses, including the Development and Well-Being Assessment and the attention deficit hyperactivity disorder rating scale. The Autism Spectrum Screening Questionnaire and the Positive and Negative Syndrome Scale were used to screen for autistic traits and psychotic symptoms, respectively. The cognitive assessments were made by a clinical psychologist using the Wechsler Preschool and Primary Scale of Intelligence, Third Edition, the Wechsler Intelligence Scale for Children, Fourth Edition, or the Wechsler Adult Intelligence Scale, Fourth Edition. Measurements and Results: In the post-H1N1 vaccination (PHV) narcolepsy group (n = 31), 43% of patients had psychiatric comorbidity, 29% had attention deficit hyperactivity disorder (ADHD) inattentive type, 20% had major depression, 10% had general anxiety disorder, 7% had oppositional defiant disorder (ODD), 3% had pervasive developmental disorder not otherwise specified (i.e., atypical autism), and 3% had eating disorder not otherwise specified (anorectic type). In the non–post-H1N1 vaccination (nPHV) narcolepsy group, one of seven patients had ADHD, inattentive type and ODD. The most frequent psychiatric symptom was temper tantrums, which occurred in 94% of the patients in the PHV group and 71% of the patients in the nPHV narcolepsy group. The cognitive assessment profile was similar in both groups and showed normal results for mean full-scale IQ and perceptual speed but decreased verbal comprehension and working memory. Patients with

  14. Influenza vaccine effectiveness estimates in Croatia in 2010-2011: a season with predominant circulation of A(H1N1)pdm09 influenza virus.

    PubMed

    Kurečić Filipović, S; Gjenero-Margan, I; Kissling, E; Kaić, B; Cvitković, A

    2015-09-01

    This is a retrospective study using the test-negative case-control method to estimate seasonal 2010-2011 influenza vaccine effectiveness (VE) in Croatia. Of patients consulting a physician for influenza-like illness (ILI) and for whom a swab was taken, we compared RT-PCR influenza-positive and RT-PCR influenza-negative patients. We used a structured questionnaire and physicians' records to obtain information on vaccination status and potential confounders. We conducted a complete case analysis using logistic regression to measure adjusted VE overall, against A(H1N1)pdm09 and in age groups. Out of 785 interviewed patients, 495 eligible patients were included in the study, after applying exclusion criteria [217 cases, of which 92·6% were A(H1N1)pdm09 positive, 278 controls]. Crude VE was 31·9% [95% confidence interval (CI) -40·9 to 67·1] and adjusted VE was 20·7% (95% CI -71·4 to 63·3), with higher VE in youngest and oldest age groups. Results from this first VE study in Croatia suggest a low to moderate VE for the 2010-2011 season. Studies year on year are needed with a greater sample size to provide more precise estimates, and also by age group and risk groups for vaccination.

  15. Best practice model for immunization: one home care agency's experience providing H1N1 and seasonal vaccine.

    PubMed

    Rolfe, Elizabeth; Howard, Leigh Ann

    2010-10-01

    This article may serve as a framework for school-based immunization initiatives. During the fall of 2009, VNA Home Health & Hospice, in close collaboration with the Maine Centers for Disease Control, organized and performed over 113 school-based clinics. These efforts helped Maine achieve a very high percentage of vaccination rates in the state's school-age population.

  16. Costs of School-Located Influenza Vaccination Clinics in Maine during the 2009-2010 H1N1 Pandemic

    ERIC Educational Resources Information Center

    Cho, Bo-Hyun; Asay, Garrett R. Beeler; Lorick, Suchita A.; Tipton, Meredith L.; Dube, Nancy L.; Messonnier, Mark L.

    2012-01-01

    This study retrospectively estimated costs for a convenience sample of school-located vaccination (SLV) clinics conducted in Maine during the 2009-2010 influenza season. Surveys were developed to capture the cost of labor including unpaid volunteers as well as supplies and materials used in SLV clinics. Six nurses from different school districts…

  17. No Evidence for Disease History as a Risk Factor for Narcolepsy after A(H1N1)pdm09 Vaccination

    PubMed Central

    Lamb, Favelle; Ploner, Alexander; Fink, Katharina; Maeurer, Markus; Bergman, Peter; Piehl, Fredrik; Weibel, Daniel; Sparén, Pär; Dahlström, Lisen Arnheim

    2016-01-01

    Objectives To investigate disease history before A(H1N1)pdm09 vaccination as a risk factor for narcolepsy. Methods Case-control study in Sweden. Cases included persons referred for a Multiple Sleep Latency Test between 2009 and 2010, identified through diagnostic sleep centres and confirmed through independent review of medical charts. Controls, selected from the total population register, were matched to cases on age, gender, MSLT-referral date and county of residence. Disease history (prescriptions and diagnoses) and vaccination history was collected through telephone interviews and population-based healthcare registers. Conditional logistic regression was used to investigate disease history before A(H1N1)pdm09 vaccination as a risk-factor for narcolepsy. Results In total, 72 narcolepsy cases and 251 controls were included (range 3–69 years mean19-years). Risk of narcolepsy was increased in individuals with a disease history of nervous system disorders (OR range = 3.6–8.8) and mental and behavioural disorders (OR = 3.8, 95% CI 1.6–8.8) before referral. In a second analysis of vaccinated individuals only, nearly all initial associations were no longer statistically significant and effect sizes were smaller (OR range = 1.3–2.6). A significant effect for antibiotics (OR = 0.4, 95% CI 0.2–0.8) and a marginally significant effect for nervous system disorders was observed. In a third case-only analysis, comparing cases referred before vaccination to those referred after; prescriptions for nervous system disorders (OR = 26.0 95% CI 4.0–170.2) and ADHD (OR = 35.3 95% CI 3.4–369.9) were statistically significant during the vaccination period, suggesting initial associations were due to confounding by indication. Conclusion The findings of this study do not support disease history before A(H1N1)pdm09 vaccination as a risk factor for narcolepsy. PMID:27120092

  18. Costs of school-located influenza vaccination clinics in Maine during the 2009-2010 H1N1 pandemic.

    PubMed

    Cho, Bo-Hyun; Asay, Garrett R Beeler; Lorick, Suchita A; Tipton, Meredith L; Dube, Nancy L; Messonnier, Mark L

    2012-10-01

    This study retrospectively estimated costs for a convenience sample of school-located vaccination (SLV) clinics conducted in Maine during the 2009-2010 influenza season. Surveys were developed to capture the cost of labor including unpaid volunteers as well as supplies and materials used in SLV clinics. Six nurses from different school districts completed a clinic day survey on staff time; four of the six also provided data for materials and supplies. For all clinics, average per-dose labor cost was estimated at $5.95. Average per-dose material cost, excluding vaccine, was $5.76. From the four complete clinic survey responses, total per-dose cost was estimated to be an average of $13.51 (range = $4.91-$32.39). Use of donated materials and uncompensated volunteer staff could substantially reduce per-dose cost. Average per-dose cost could also be lowered by increasing the number of doses administered in a clinic.

  19. GENE SIGNATURES ASSOCIATED WITH ADAPTIVE HUMORAL IMMUNITY FOLLOWING SEASONAL INFLUENZA A/H1N1 VACCINATION

    PubMed Central

    Ovsyannikova, Inna G.; Salk, Hannah M.; Kennedy, Richard B.; Haralambieva, Iana H.; Zimmermann, Michael T.; Grill, Diane E.; Oberg, Ann L.; Poland, Gregory A.

    2016-01-01

    This study aimed to identify gene expression markers shared between both influenza hemagglutination-inhibition (HAI) and virus-neutralization antibody (VNA) responses. We enrolled 158 older subjects who received the 2010–2011 trivalent inactivated influenza vaccine (TIV). Influenza-specific HAI and VNA titers, and mRNA-sequencing were performed using blood samples obtained at Days 0, 3 and 28 post-vaccination. For antibody response at Day 28 vs Day 0, several genesets were identified as significant in predictive models for HAI (n=7) and VNA (n=35) responses. Five genesets (comprising the genes MAZ, TTF, GSTM, RABGGTA, SMS, CA, IFNG, and DOPEY) were in common for both HAI and VNA. For response at Day 28 vs Day 3, many genesets were identified in predictive models for HAI (n=13) and VNA (n=41). Ten genesets (comprising biologically related genes, such as MAN1B1, POLL, CEBPG, FOXP3, IL12A, TLR3, TLR7, and others) were shared between HAI and VNA. These identified genesets demonstrated a high degree of network interactions and likelihood for functional relationships. Influenza-specific HAI and VNA responses demonstrated a remarkable degree of similarity. Although unique geneset signatures were identified for each humoral outcome, several genesets were determined to be in common with both HAI and VNA response to influenza vaccine. PMID:27534615

  20. The Lao Experience in Deploying Influenza A(H1N1)pdm09 Vaccine: Lessons Made Relevant in Preparing for Present Day Pandemic Threats.

    PubMed

    Xeuatvongsa, Anonh; Mirza, Sara; Winter, Christian; Feldon, Keith; Vongphrachanh, Phengta; Phonekeo, Darouny; Denny, Justin; Khanthamaly, Viengphone; Kounnavong, Bounheuang; Lylianou, Doualy; Phousavath, Sisouphane; Norasingh, Sisouveth; Boutta, Nao; Olsen, Sonja; Bresee, Joseph; Moen, Ann; Corwin, Andrew

    2015-01-01

    The Lao PDR, as did most countries of the Mekong Region, embarked on a pandemic vaccine initiative to counter the threat posed by influenza A(H1N1)pdm09. Overall, estimated vaccine coverage of the Lao population was 14%, with uptake in targeted health care workers and pregnant women 99% and 41%, respectively. Adverse Events Following Immunization accounted for only 6% of survey driven, reported vaccination experiences, with no severe consequences or deaths. Public acceptability of the vaccine campaign was high (98%). Challenges to vaccine deployment included: 1) no previous experience in fielding a seasonal influenza vaccine, 2) safety and efficacy concerns, and 3) late arrival of vaccine 10 months into the pandemic. The Lao success in surmounting these hurdles was in large measure attributed to the oversight assigned the National Immunization Program, and national sensitivities in responding to the avian influenza A(H5N1) crisis in the years leading up to the pandemic. The Lao "lessons learned" from pandemic vaccine deployment are made even more relevant four years on, given the many avian influenza strains circulating in the region, all with pandemic potential.

  1. Pitfalls in anti-influenza T cell detection by Elispot using thimerosal containing pandemic H1N1 vaccine as antigen.

    PubMed

    Chauvat, A; Benhamouda, N; Loison, E; Gougeon, M L; Gey, A; Levionnois, E; Ravel, P; Abitbol, V; Roncelin, S; Marcheteau, E; Quintin-Colonna, F; Fridman, W H; Launay, O; Tartour, E

    2012-04-30

    Monitoring T cells in combination with humoral response may be of value to predict clinical protection and cross-protective immunity after influenza vaccination. Elispot technique which measures cytokine produced after antigen-specific T cell stimulation is used routinely to detect and characterize anti-viral T cells. We found that the preservative thimerosal present in most H1N1 pandemic vaccines, induced in vitro abortive activation of T cells followed by cell death leading to false-positive results with the Elispot technique. The size of the spots, usually not measured in routine analysis, appears to be a discriminative criterion to detect this bias. Multi-dose vials of vaccine containing thimerosal remain important for vaccine delivery and our results alert about false-positive results of Elispot to monitor the clinical efficacy of these vaccines. We showed that this finding extends for other T cell monitoring techniques based on cytokine production such as ELISA. Although measuring in vitro immune response using the whole vaccine used for human immunization directly reflects in vivo global host response to the vaccine, the present study strongly supports the use of individual vaccine components for immune monitoring due to the presence of contaminants, such as thimerosal, leading to a bias in interpretation of the results.

  2. Serum-Free Suspension Culture of MDCK Cells for Production of Influenza H1N1 Vaccines.

    PubMed

    Huang, Ding; Peng, Wen-Juan; Ye, Qian; Liu, Xu-Ping; Zhao, Liang; Fan, Li; Xia-Hou, Kang; Jia, Han-Jing; Luo, Jian; Zhou, Lin-Ting; Li, Bei-Bei; Wang, Shi-Lei; Xu, Wen-Ting; Chen, Ze; Tan, Wen-Song

    2015-01-01

    Development of serum-free suspension cell culture processes is very important for influenza vaccine production. Previously, we developed a MDCK suspension cell line in a serum-free medium. In the present study, the growth kinetics of suspension MDCK cells and influenza virus production in the serum-free medium were investigated, in comparison with those of adherent MDCK cells in both serum-containing and serum-free medium. It was found that the serum-free medium supported the stable subculture and growth of both adherent and suspension cells. In batch culture, for both cell lines, the growth kinetics in the serum-free medium was comparable with those in the serum-containing medium and a commercialized serum-free medium. In the serum-free medium, peak viable cell density (VCD), haemagglutinin (HA) and median tissue culture infective dose (TCID50) titers of the two cell lines reached 4.51×106 cells/mL, 2.94Log10(HAU/50 μL) and 8.49Log10(virions/mL), and 5.97×106 cells/mL, 3.88Log10(HAU/50 μL), and 10.34Log10(virions/mL), respectively. While virus yield of adherent cells in the serum-free medium was similar to that in the serum-containing medium, suspension culture in the serum-free medium showed a higher virus yield than adherent cells in the serum-containing medium and suspension cells in the commercialized serum-free medium. However, the percentage of infectious viruses was lower for suspension culture in the serum-free medium. These results demonstrate the great potential of this suspension MDCK cell line in serum-free medium for influenza vaccine production and further improvements are warranted.

  3. A De-O-acylated Lipooligosaccharide-Based Adjuvant System Promotes Antibody and Th1-Type Immune Responses to H1N1 Pandemic Influenza Vaccine in Mice

    PubMed Central

    Ryu, Ji In; Park, Shin Ae; Wui, Seo Ri; Ko, Ara; Han, Ji Eun; Choi, Jung Ah; Kim, Kwang Sung; Cho, Yang Je

    2016-01-01

    Vaccine adjuvants are agents that are used to promote immune responses to vaccine antigens and thereby to enhance the protective efficacy of the vaccines. In this study, we investigated the adjuvant activity of CIA06, an adjuvant system that is composed of a toll-like receptor 4 agonist de-O-acylated lipooligosaccharide (dLOS) and aluminum hydroxide, on the H1N1 pandemic influenza vaccine Greenflu-S® in mice. CIA06 significantly enhanced influenza-specific serum IgG, hemagglutination-inhibition, and virus-neutralizing antibody titers, which eliminated vaccine dose-dependency in the antibody response. Mice immunized with the CIA06-adjuvanted Greenflu-S showed Th1-type-predominant cytokine profiles, and both CD4+ and CD8+ T cell responses were induced. Immunization of mice with the CIA06-adjuvanted vaccine reduced the mortality and morbidity of mice upon lethal challenges with influenza virus, and no excessive inflammatory responses were observed in the lung tissues of the immunized mice after viral infection. These data suggest that the dLOS-based adjuvant system CIA06 can be used to promote the immune responses to influenza vaccine or to spare antigen dose without causing harmful inflammatory responses. PMID:27891512

  4. Punctuated Evolution of Influenza Virus Neuraminidase (A/H1N1) under Opposing Migration and Vaccination Pressures

    PubMed Central

    Phillips, J. C.

    2014-01-01

    Influenza virus contains two highly variable envelope glycoproteins, hemagglutinin (HA) and neuraminidase (NA). The structure and properties of HA, which is responsible for binding the virus to the cell that is being infected, change significantly when the virus is transmitted from avian or swine species to humans. Here we focus first on the simpler problem of the much smaller human individual evolutionary amino acid mutational changes in NA, which cleaves sialic acid groups and is required for influenza virus replication. Our thermodynamic panorama shows that very small amino acid changes can be monitored very accurately across many historic (1945–2011) Uniprot and NCBI strains using hydropathicity scales to quantify the roughness of water film packages. Quantitative sequential analysis is most effective with the fractal differential hydropathicity scale based on protein self-organized criticality (SOC). Our analysis shows that large-scale vaccination programs have been responsible for a very large convergent reduction in common influenza severity in the last century. Hydropathic analysis is capable of interpreting and even predicting trends of functional changes in mutation prolific viruses directly from amino acid sequences alone. An engineered strain of NA1 is described which could well be significantly less virulent than current circulating strains. PMID:25143953

  5. 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

  6. Influenza H1N1 (swine flu) vaccination: a safety surveillance feasibility study using self-reporting of serious adverse events and pregnancy outcomes

    PubMed Central

    Mackenzie, Isla S; MacDonald, Thomas M; Shakir, Saad; Dryburgh, Moira; Mantay, Brian J; McDonnell, Patrick; Layton, Deborah

    2012-01-01

    AIMS During the global H1N1 influenza A (swine flu) pandemic 2009–2010, swine flu vaccines were expeditiously licensed and a mass vaccination programme for high risk groups, including pregnant women, was introduced in the UK. This pilot active safety surveillance study was performed to establish the feasibility of rapidly monitoring the new swine flu vaccines in large patient numbers receiving or offered the vaccination under normal conditions of use within a short time frame. METHODS A cohort design with safety data capture through modern technologies was carried out in Scotland, UK during the winter swine flu vaccination programme 2009–2010 in individuals receiving or offered the swine flu vaccination. The main outcome measures were self-reported serious adverse events (SAEs) and pregnancy outcomes. RESULTS The cohort comprised 4066 people; 3754 vaccinated and 312 offered the vaccination but not vaccinated. There were 939 self-reported events (838 different events), 53 judged to fit SAE criteria by the investigators, with nine judged as possibly, probably or definitely vaccine related. None of the seven deaths (six in vaccinees) were judged as vaccine related. One hundred and twenty-eight women reported 130 pregnancies during the study with 117 pregnant at study start. There were reports of four miscarriages in three women and six possible congenital abnormalities in live births. CONCLUSIONS Overall, no significant safety issues were identified. The methodology and use of modern technologies to collect safety data from large numbers of patients was successful and could be used again in similar safety studies. PMID:22082196

  7. 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.

  8. Risk of Narcolepsy after AS03 Adjuvanted Pandemic A/H1N1 2009 Influenza Vaccine in Adults: A Case-Coverage Study in England

    PubMed Central

    Stowe, Julia; Andrews, Nicholas; Kosky, Christopher; Dennis, Gary; Eriksson, Sofia; Hall, Andrew; Leschziner, Guy; Reading, Paul; Shneerson, John M.; Donegan, Katherine; Miller, Elizabeth

    2016-01-01

    Study Objectives: An increased risk of narcolepsy has been observed in children following ASO3-adjuvanted pandemic A/H1N1 2009 (Pandemrix) vaccine. We investigated whether this risk extends to adults in England. Methods: Six adult sleep centers in England were visited between November 2012 and February 2014 and vaccination/clinical histories obtained from general practitioners. Suspected narcolepsy cases aged older than 17 y were selected. The risk of narcolepsy following Pandemrix was calculated using cases diagnosed by the time of the center visits and those with a diagnosis by November 30, 2011 after which there was increased awareness of the risk in children. The odds of vaccination in cases and in matched population data were compared using a case-coverage design. Results: Of 1,446 possible cases identified, most had onset before 2009 or were clearly not narcolepsy. Of the 60 remaining cases, 20 were excluded after expert review, leaving 40 cases with narcolepsy; 5 had received Pandemrix between 3 and 18 mo before onset. All the vaccinated cases had cataplexy, two received a diagnosis by November 2011 and two were aged 40 y or older. The odds ratio for vaccination in cases compared to the population was 4.24 (95% confidence interval 1.45–12.38) using all cases and 9.06 (1.90–43.17) using cases with a diagnosis by November 2011, giving an attributable risk of 0.59 cases per 100,000 doses. Conclusions: We found a significantly increased risk of narcolepsy in adults following Pandemrix vaccination in England. The risk was lower than that seen in children using a similar study design. Citation: Stowe J, Andrews N, Kosky C, Dennis G, Eriksson S, Hall A, Leschziner G, Reading P, Shneerson JM, Donegan K, Miller E. Risk of narcolepsy after AS03 adjuvanted pandemic A/H1N1 2009 influenza vaccine in adults: a case-coverage study in England. SLEEP 2016;39(5):1051–1057. PMID:26856903

  9. Immunogenicity and Cross Protection in Mice Afforded by Pandemic H1N1 Live Attenuated Influenza Vaccine Containing Wild-Type Nucleoprotein

    PubMed Central

    Isakova-Sivak, Irina; Petukhova, Galina; Korenkov, Daniil; Losev, Igor; Smolonogina, Tatiana; Tretiak, Tatiana; Donina, Svetlana; Shcherbik, Svetlana; Bousse, Tatiana; Rudenko, Larisa

    2017-01-01

    Since conserved viral proteins of influenza virus, such as nucleoprotein (NP) and matrix 1 protein, are the main targets for virus-specific CD8+ cytotoxic T-lymphocytes (CTLs), we hypothesized that introduction of the NP gene of wild-type virus into the genome of vaccine reassortants could lead to better immunogenicity and afford better protection. This paper describes in vitro and in vivo preclinical studies of two new reassortants of pandemic H1N1 live attenuated influenza vaccine (LAIV) candidates. One had the hemagglutinin (HA) and neuraminidase (NA) genes from A/South Africa/3626/2013 H1N1 wild-type virus on the A/Leningrad/134/17/57 master donor virus backbone (6 : 2 formulation) while the second had the HA, NA, and NP genes of the wild-type virus on the same backbone (5 : 3 formulation). Although both LAIVs induced similar antibody immune responses, the 5 : 3 LAIV provoked greater production of virus-specific CTLs than the 6 : 2 variant. Furthermore, the 5 : 3 LAIV-induced CTLs had higher in vivo cytotoxic activity, compared to 6 : 2 LAIV. Finally, the 5 : 3 LAIV candidate afforded greater protection against infection and severe illness than the 6 : 2 LAIV. Inclusion in LAIV of the NP gene from wild-type influenza virus is a new approach to inducing cross-reactive cell-mediated immune responses and cross protection against pandemic influenza. PMID:28210631

  10. 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

  11. 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

    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

    2013-05-01

    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.

  12. Effects of immunizing school children with 2009 influenza A (H1N1) monovalent vaccine on absenteeism among students and teachers in Maine.

    PubMed

    Graitcer, Samuel B; Dube, Nancy L; Basurto-Davila, Ricardo; Smith, Peter F; Ferdinands, Jill; Thompson, Mark; Uzicanin, Amra; Gargiullo, Paul; Chaves, Sandra S; Robinson, Sara; Sears, Stephen; Tipton, Meredith; Monto, Arnold S; Mills, Dora; Shay, David K

    2012-07-06

    The overall and indirect effects of immunizing school children with influenza A (H1N1) 2009 pandemic virus vaccine prior to and during the peak of virus circulation were evaluated on student and teacher school absenteeism. We used records collected from late 2009 through early 2010 from schools in four Maine counties. Mixed logistic regression models were used to estimate the daily association between school-level immunization coverage and absenteeism by level of influenza activity, after adjusting for the proportion of students receiving reduced-cost lunches, student minority status, absences adjacent to weekends and Thanksgiving, rural school location, and the circulation of other respiratory viruses. Increasing student immunization coverage was associated with reduced absenteeism during periods of high influenza activity. For example, as immunization coverage during the peak week of pandemic virus circulation increased from 38% to 69% (the 10th and 90th percentiles of observed coverage, respectively), relative reductions in daily absenteeism among all students, unimmunized students, and teachers were 8.2% (95% confidence interval [CI]: 6.5, 9.9), 5.7% (95% CI: 4.2, 7.3), and 8.7% (95% CI: 1.3, 16), respectively. Increased vaccination coverage among school-aged Maine children had modest overall and indirect effects on student and teacher absenteeism, despite vaccination occurring just prior and during peak pandemic virus circulation.

  13. 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

  14. Narcolepsy, 2009 A(H1N1) pandemic influenza, and pandemic influenza vaccinations: what is known and unknown about the neurological disorder, the role for autoimmunity, and vaccine adjuvants.

    PubMed

    Ahmed, S Sohail; Schur, Peter H; MacDonald, Noni E; Steinman, Lawrence

    2014-05-01

    The vaccine safety surveillance system effectively detected a very rare adverse event, narcolepsy, in subjects receiving AS03-adjuvanted A(H1N1) pandemic vaccine made using the European inactivation/purification protocol. The reports of increased cases of narcolepsy in non-vaccinated subjects infected with wild A(H1N1) pandemic influenza virus suggest a role for the viral antigen(s) in disease development. However, additional investigations are needed to better understand what factor(s) in wild influenza infection trigger(s) narcolepsy in susceptible hosts. An estimated 31 million doses of European AS03-adjuvanted A(H1N1) pandemic vaccine were used in more than 47 countries. The Canadian AS03-adjuvanted A(H1N1) pandemic vaccine was used with high coverage in Canada where an estimated 12 million doses were administered. As no similar narcolepsy association has been reported to date with the AS03-adjuvanted A(H1N1) pandemic vaccine made using the Canadian inactivation/purification protocol, this suggests that the AS03 adjuvant alone may not be responsible for the narcolepsy association. To date, no narcolepsy association has been reported with the MF59®-adjuvanted A(H1N1) pandemic vaccine. This review article provides a brief background on narcolepsy, outlines the different types of vaccine preparations including the ones for influenza, reviews the accumulated evidence for the safety of adjuvants, and explores the association between autoimmune diseases and natural infections. It concludes by assimilating the historical observations and recent clinical studies to formulate a feasible hypothesis on why vaccine-associated narcolepsy may not be solely linked to the AS03 adjuvant but more likely be linked to how the specific influenza antigen component of the European AS03-adjuvanted pandemic vaccine was prepared. Careful and long-term epidemiological studies of subjects who developed narcolepsy in association with AS03-adjuvanted A(H1N1) pandemic vaccine prepared with

  15. Upregulation of IL-21 Receptor on B Cells and IL-21 Secretion Distinguishes Novel 2009 H1N1 Vaccine Responders from Nonresponders among HIV-Infected Persons on Combination Antiretroviral Therapy

    PubMed Central

    Pallikkuth, Suresh; Kanthikeel, Sudheesh Pilakka; Silva, Sandra Y.; Fischl, Margaret; Pahwa, Rajendra; Pahwa, Savita

    2011-01-01

    Mechanisms underlying failure of novel 2009 H1N1 influenza vaccine-induced Ab responses in HIV-infected persons are poorly understood. This study prospectively evaluated 16 HIV-infected patients on combination antiretroviral therapy and eight healthy controls (HC) who received a single 15 μg dose of nonadjuvanted novel 2009 H1N1 influenza vaccine during the 2009 H1N1 epidemic. Peripheral blood was collected at baseline (T0) and at 7 d (T1) and 28 d (T2) postvaccination for evaluation of immune responses. Prevaccination hemagglutination inhibition Ab titer was <1:20 in all except one study participant. At T2, all HC and 8 out of 16 patients (50%) developed a vaccine-induced Ab titer of ≥1:40. Vaccine responder (R) and vaccine nonresponder patients were comparable at T0 in age, CD4 counts, virus load, and B cell immunophenotypic characteristics. At T2, HC and R patients developed an expansion of phenotypic and functional memory B cells and ex vivo H1N1-stimulated IgG Ab-secreting cells in an ELISPOT assay. The memory B cell response was preceded by a significant expansion of plasmablasts and spontaneous H1N1-specific Ab-secreting cells at T1. At T2, HC and R patients also exhibited significant increases in serum IL-21 levels and in the frequency and mean fluorescence intensity of IL-21R–expressing B cells, which correlated with serum H1N1 Ab titers. Vaccine nonresponder patients failed to develop the above-described vaccine-induced immunologic responses. The novel association of novel 2009 H1N1 vaccine-induced Ab responses with IL-21/IL-21R upregulation and with development of memory B cells and plasmablasts has implications for future research in vaccine design. PMID:21531891

  16. Comparison of live, attenuated H1N1 and H3N2 cold-adapted and avian-human influenza A reassortant viruses and inactivated virus vaccine in adults.

    PubMed

    Sears, S D; Clements, M L; Betts, R F; Maassab, H F; Murphy, B R; Snyder, M H

    1988-12-01

    The infectivity, immunogenicity, and efficacy of live, attenuated influenza A/Texas/1/85 (H1N1) and A/Bethesda/1/85 (H3N2) avian-human (ah) and cold-adapted (ca) reassortant vaccines were compared in 252 seronegative adult volunteers. The immunogenicity and efficacy of the H1N1 reassortant vaccine were also compared with those of the trivalent inactivated virus vaccine. Each reassortant vaccine was satisfactorily attenuated. The 50% human infectious dose was 10(4.9) for ca H1N1, 10(5.4) for ah H1N1, 10(6.4) for ca H3N2, and 10(6.5) TCID50 for ah H3N2 reassortant virus. Within a subtype, the immunogenicities of ah and ca vaccines were comparable. Five to seven weeks after vaccination, volunteers were challenged with homologous wild-type influenza A virus. The magnitude of shedding of virus after challenge was greater than 100-fold less in H1N1 vaccinees and greater than 10-fold less in H3N2 vaccinees compared with unimmunized controls. The vaccines were equally efficacious, as indicated by an 86%-100% reduction in illness. Thus, the ah A/Mallard/New York/6750/78 and the ca A/Ann Arbor/6/60 reassortant viruses are comparable.

  17. 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

    Broadbent, Andrew J; Santos, Celia P; Anafu, Amanda; Wimmer, Eckard; Mueller, Steffen; Subbarao, Kanta

    2016-01-20

    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 (∼10(6)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 10(3) to 10(5) 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.

  18. 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

  19. Design of a shear-thinning recoverable peptide hydrogel from native sequences and application for influenza H1N1 vaccine adjuvant

    SciTech Connect

    Huang, Hongzhou; Shi, Jishu; Laskin, Julia; Liu, Ziyan; McVey, David S.; Sun, Xiuzhi S.

    2011-10-07

    Peptide hydrogels are considered injectable materials for drug delivery and tissue engineering applications. Most published hydrogel-forming sequences contain either alternating-charged and noncharged residues or amphiphilic blocks. Here, we report a self-assembling peptide, h9e (FLIVIGSIIGPGGDGPGGD), designed by rationally combining two native sequences from an elastic segment of spider silk and a trans-membrane segment of human muscle L-type calcium channel. The turning segment GSII of h9e promoted hydrogel formation in both Ca2+ solution and acidic pH conditions at water content greater than 99.5%. Although h9e Ca2+ hydrogel and h9e acidic hydrogel have the same sequence, they have distinct physical properties. The shear-thinning, rapid-strengthrecovering h9e Ca2+ hydrogel was used as an H1N1 influenza vaccine adjuvant. The h9e adjuvant was biologically safe and improved immune response by 70% compared with an oil-based commercial adjuvant.

  20. 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.

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

    PubMed Central

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

    2015-01-01

    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. PMID:26615216

  2. 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.

  3. Safety and persistence of the humoral and cellular immune responses induced by 2 doses of an AS03-adjuvanted A(H1N1)pdm09 pandemic influenza vaccine administered to infants, children and adolescents: Two open, uncontrolled studies.

    PubMed

    Garcia-Sicilia, José; Arístegui, Javier; Omeñaca, Félix; Carmona, Alfonso; Tejedor, Juan C; Merino, José M; García-Corbeira, Pilar; Walravens, Karl; Bambure, Vinod; Moris, Philippe; Caplanusi, Adrian; Gillard, Paul; Dieussaert, Ilse

    2015-01-01

    In children, 2 AS03-adjuvanted A(H1N1)pdm09 vaccine doses given 21 days apart were previously shown to induce a high humoral immune response and to have an acceptable safety profile up to 42 days following the first vaccination. Here, we analyzed the persistence data from 2 open-label studies, which assessed the safety, and humoral and cell-mediated immune responses induced by 2 doses of this vaccine. The first study was a phase II, randomized trial conducted in 104 children aged 6-35 months vaccinated with the A(H1N1)pdm09 vaccine containing 1.9 µg haemagglutinin antigen (HA) and AS03B (5.93 mg tocopherol) and the second study, a phase III, non-randomized trial conducted in 210 children and adolescents aged 3-17 years vaccinated with the A(H1N1)pdm09 vaccine containing 3.75 µg HA and AS03A (11.86 mg tocopherol). Approximately one year after the first dose, all children with available data were seropositive for haemagglutinin inhibition and neutralising antibody titres, but a decline in geometric mean antibody titres was noted. The vaccine induced a cell-mediated immune response in terms of antigen-specific CD4(+) T-cells, which persisted up to one year post-vaccination. The vaccine did not raise any safety concern, though these trials were not designed to detect rare events. In conclusion, 2 doses of the AS03-adjuvanted A(H1N1)pdm09 vaccine at 2 different dosages had a clinically acceptable safety profile, and induced high and persistent humoral and cell-mediated immune responses in children aged 6-35 months and 3-17 years. These studies have been registered at www.clinicaltrials.gov NCT00971321 and NCT00964158.

  4. 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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  5. Effect on Cellular and Humoral Immune Responses of the AS03 Adjuvant System in an A/H1N1/2009 Influenza Virus Vaccine Administered to Adults during Two Randomized Controlled Trials ▿ †

    PubMed Central

    Roman, François; Clément, Frédéric; Dewé, Walthère; Walravens, Karl; Maes, Cathy; Willekens, Julie; De Boever, Fien; Hanon, Emmanuel; Leroux-Roels, Geert

    2011-01-01

    The influence of AS03A, a tocopherol oil-in-water emulsion-based adjuvant system, on humoral and cell-mediated responses to A/California/7/2009 H1N1 pandemic vaccine was investigated. In two observer-blind studies, a total of 261 healthy adults aged 18 to 60 years were randomized to receive either AS03A-adjuvanted H1N1 vaccine containing 3.75 μg hemagglutinin (HA) or nonadjuvanted H1N1 vaccine containing 15 or 3.75 μg HA on days 0 and 21. Hemagglutination inhibition (HI) antibody and T-cell responses were analyzed up to day 42. A first dose of AS03A-adjuvanted vaccine (3.75 μg HA) or nonadjuvanted vaccine (15 μg HA) induced HI responses of similar magnitudes that exceeded licensure criteria (e.g., 94 to 100% with titers of ≥40). A lower response following 3.75 μg HA without adjuvant was observed (73% with titers of ≥40). Following a second dose, geometric mean HI titers at day 42 were higher for AS03A-adjuvanted vaccine (636 and 637) relative to nonadjuvanted vaccine (341 for 15 μg HA and 150 for 3.75 μg HA). Over the 42-day period, the increase in frequency of A/H1N1/2009-specific CD4+ T cells was significantly higher in the adjuvanted group than in the nonadjuvanted group. There was no evidence of correlation between baseline CD4+ T-cell frequencies and day 21 HI antibody titers, while there was some correlation (R = 0.35) between day 21 CD4+ T-cell frequencies and day 42 HI titers. AS03A adjuvant enhanced the humoral and CD4+ T-cell-mediated responses to A/H1N1/2009 vaccine. Baseline A/H1N1/2009-specific CD4+ T-cell frequencies did not predict post-dose 1 antibody responses, but there was some correlation between post-dose 1 CD4+ T-cell frequencies and post-dose 2 antibody responses. PMID:21450978

  6. Live attenuated influenza A virus vaccine protects against heterologous challenge with A(H1N1)pdm09 without inducing vaccine associated enhanced respiratory disease

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Influenza A virus (IAV) vaccines that provide broad cross-protection against antigenic variants are necessary to prevent infection and shedding of the wide array of IAV cocirculating in swine. Whole inactivated virus (WIV) vaccines provide only partial protection against IAV with substantial antigen...

  7. Immune responses elicited to a live-attenuated influenza virus vaccine compared to a traditional whole-inactivated virus vaccine for pandemic H1N1in pigs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In the United States there are currently two influenza vaccine platforms approved for use in humans - conventional inactivated virus and live-attenuated influenza virus (LAIV). One of the major challenges for influenza vaccination is designing a platform that provides cross-protection across strains...

  8. Protection against H5N1 highly pathogenic avian and pandemic (H1N1) 2009 influenza virus infection in cynomolgus monkeys by an inactivated H5N1 whole particle vaccine.

    PubMed

    Nakayama, Misako; Shichinohe, Shintaro; Itoh, Yasushi; Ishigaki, Hirohito; Kitano, Mitsutaka; Arikata, Masahiko; Pham, Van Loi; Ishida, Hideaki; Kitagawa, Naoko; Okamatsu, Masatoshi; Sakoda, Yoshihiro; Ichikawa, Takaya; Tsuchiya, Hideaki; Nakamura, Shinichiro; Le, Quynh Mai; Ito, Mutsumi; Kawaoka, Yoshihiro; Kida, Hiroshi; Ogasawara, Kazumasa

    2013-01-01

    H5N1 highly pathogenic avian influenza virus (HPAIV) infection has been reported in poultry and humans with expanding clade designations. Therefore, a vaccine that induces immunity against a broad spectrum of H5N1 viruses is preferable for pandemic preparedness. We established a second H5N1 vaccine candidate, A/duck/Hokkaido/Vac-3/2007 (Vac-3), in our virus library and examined the efficacy of inactivated whole particles of this strain against two clades of H5N1 HPAIV strains that caused severe morbidity in cynomolgus macaques. Virus propagation in vaccinated macaques infected with either of the H5N1 HPAIV strains was prevented compared with that in unvaccinated macaques. This vaccine also prevented propagation of a pandemic (H1N1) 2009 virus in macaques. In the vaccinated macaques, neutralization activity, which was mainly shown by anti-hemagglutinin antibody, against H5N1 HPAIVs in plasma was detected, but that against H1N1 virus was not detected. However, neuraminidase inhibition activity in plasma and T-lymphocyte responses in lymph nodes against H1N1 virus were detected. Therefore, cross-clade and heterosubtypic protective immunity in macaques consisted of humoral and cellular immunity induced by vaccination with Vac-3.

  9. [Antibody response to trivalent anti-influenza vaccination (inactivated virus) A/Texas/1/77 H3N2), A/URSS/90/77 (H1N1), B/Hong Kong/8/73].

    PubMed

    Mancini, G; Andreoni, M; Arangio-Ruiz, G; Sarrecchia, C; Donatelli, I; Resta, S; Rozera, C; Sordillo, P; Rocchi, G

    1982-05-01

    Seventy-five young recruits received an intramuscular dose of anti-influenza virus vaccine containing 300 U.I. of A/Texas/1/77 (H3N2), A/URSS/90/77 (H1N1), B/Hong Kong/8/73 strains. Antibody responses were detected by HI and SRH tests: immunogenicity of the preparation was different for the individual vaccine strain in spite of the similar amount of antigenic content, and the immunity conferred by vaccine strains did not significantly extend to new influenza virus strains which prevailed in 1979/80 winter season with the exception for A/Brazil/11/78 (H1N1).

  10. Concurrent and cross-season protection of inactivated influenza vaccine against A(H1N1)pdm09 illness among young children: 2012-2013 case-control evaluation of influenza vaccine effectiveness.

    PubMed

    Fu, Chuanxi; Xu, Jianxiong; Lin, Jinyan; Wang, Ming; Li, Kuibiao; Ge, Jing; Thompson, Mark G

    2015-06-09

    In 2012-2013, we examined 1729 laboratory-confirmed A(H1N1)pdm09 influenza cases matched 1:1 with healthy controls and estimated influenza vaccine effectiveness (VE) for trivalent inactivated influenza vaccine (IIV3) to be 67% (95% confidence interval=58-74%) for ages 8 months to 6 years old. Among children aged 8-35 months old, VE for fully vaccinated children (73%, 60-81%) was significantly higher than VE for partially vaccinated children (55%, 33-70%). Significant cross-season protection from prior IIV3 was noted, including VE of 31% (8-48%) from IIV3 received in 2010-2011 against influenza illness in 2012--2013 without subsequent boosting doses.

  11. 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.

  12. Safety and persistence of the humoral and cellular immune responses induced by 2 doses of an AS03-adjuvanted A(H1N1)pdm09 pandemic influenza vaccine administered to infants, children and adolescents: Two open, uncontrolled studies

    PubMed Central

    Garcia-Sicilia, José; Arístegui, Javier; Omeñaca, Félix; Carmona, Alfonso; Tejedor, Juan C; Merino, José M; García-Corbeira, Pilar; Walravens, Karl; Bambure, Vinod; Moris, Philippe; Caplanusi, Adrian; Gillard, Paul; Dieussaert, Ilse

    2015-01-01

    In children, 2 AS03-adjuvanted A(H1N1)pdm09 vaccine doses given 21 days apart were previously shown to induce a high humoral immune response and to have an acceptable safety profile up to 42 days following the first vaccination. Here, we analyzed the persistence data from 2 open-label studies, which assessed the safety, and humoral and cell-mediated immune responses induced by 2 doses of this vaccine. The first study was a phase II, randomized trial conducted in 104 children aged 6–35 months vaccinated with the A(H1N1)pdm09 vaccine containing 1.9 µg haemagglutinin antigen (HA) and AS03B (5.93 mg tocopherol) and the second study, a phase III, non-randomized trial conducted in 210 children and adolescents aged 3–17 years vaccinated with the A(H1N1)pdm09 vaccine containing 3.75 µg HA and AS03A (11.86 mg tocopherol). Approximately one year after the first dose, all children with available data were seropositive for haemagglutinin inhibition and neutralising antibody titres, but a decline in geometric mean antibody titres was noted. The vaccine induced a cell-mediated immune response in terms of antigen-specific CD4+ T-cells, which persisted up to one year post-vaccination. The vaccine did not raise any safety concern, though these trials were not designed to detect rare events. In conclusion, 2 doses of the AS03-adjuvanted A(H1N1)pdm09 vaccine at 2 different dosages had a clinically acceptable safety profile, and induced high and persistent humoral and cell-mediated immune responses in children aged 6–35 months and 3–17 years. These studies have been registered at www.clinicaltrials.gov NCT00971321 and NCT00964158. PMID:26176592

  13. Safety and Immunogenicity of a Monovalent 2009 Influenza A/H1N1v Vaccine Adjuvanted With AS03A or Unadjuvanted in HIV-Infected Adults: A Randomized, Controlled Trial

    PubMed Central

    Desaint, Corinne; Durier, Christine; Loulergue, Pierre; Duval, Xavier; Jacomet, Christine; Pialoux, Gilles; Ghosn, Jade; Raffi, François; Rey, David; Ajana, Faiza; Colin de Verdière, Nathalie; Reynes, Jacques; Foubert, Valérie; Roman, François; Devaster, Jeanne-Marie; Delfraissy, Jean-François; Aboulker, Jean-Pierre

    2011-01-01

    Background. Human immunodeficiency virus (HIV)–infected patients have decreased immune response to vaccines. Few data are available about pandemic flu vaccination in this population. Methods. We conducted a multicenter, patient-blinded, randomized trial in a cohort of HIV-infected adults. Patients received 2 injections 21 days apart of a AS03A-adjuvanted H1N1v vaccine containing 3.75 μg hemagglutinin (HA) or a nonadjuvanted H1N1v vaccine containing 15 μg HA to assess hemagglutination inhibition (HI) response and safety. Results. A total of 309 patients were randomized, and 306 were vaccinated. After the first vaccine dose, HI titers ≥1:40 were observed in 93.4% of the patients in the adjuvanted group (A group) (n = 155) and in 75.5% in the nonadjuvanted group (B group) (n = 151) (P < .001); seroconversion rates were 88.8% and 71.2%, and factor increases in geometric mean titers (GMT) of 21.9 and 15.1, respectively. After 2 injections, 98.6% of patients of the A group and 92.1% of the B group demonstrated HI titers ≥1:40 (P = .018); seroconversion rates were 96.5% and 87.1%, respectively, and factor increases in GMT were 45.5 and 21.2, respectively. The majority of adverse events were mild to moderate in severity; no impact on CD4+ cell count or viral load has been detected. Conclusions. In HIV-1–infected adults, the AS03A-adjuvanted H1N1v vaccine yielded a higher immune response than did the nonadjuvanted one, with no impact on HIV infection. PMID:21628666

  14. 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

  15. Establishment of Vero cell RNA polymerase I-driven reverse genetics for Influenza A virus and its application for pandemic (H1N1) 2009 influenza virus vaccine production.

    PubMed

    Song, Min-Suk; Baek, Yun Hee; Pascua, Philippe Noriel Q; Kwon, Hyeok-Il; Park, Su-Jin; Kim, Eun-Ha; Lim, Gyo-Jin; Choi, Young-Ki

    2013-06-01

    The constant threat of newly emerging influenza viruses with pandemic potential requires the need for prompt vaccine production. Here, we utilized the Vero cell polymerase I (PolI) promoter, rather than the commonly used human PolI promoter, in an established reverse-genetics system to rescue viable influenza viruses in Vero cells, an approved cell line for human vaccine production. The Vero PolI promoter was more efficient in Vero cells and demonstrated enhanced transcription levels and virus rescue rates commensurate with that of the human RNA PolI promoter in 293T cells. These results appeared to be associated with more efficient generation of A(H1N1)pdm09- and H5N1-derived vaccine seed viruses in Vero cells, whilst the rescue rates in 293T cells were comparable. Our study provides an alternative means for improving vaccine preparation by using a novel reverse-genetics system for generating influenza A viruses.

  16. Risk of confirmed Guillain-Barre syndrome following receipt of monovalent inactivated influenza A (H1N1) and seasonal influenza vaccines in the Vaccine Safety Datalink Project, 2009-2010.

    PubMed

    Greene, Sharon K; Rett, Melisa; Weintraub, Eric S; Li, Lingling; Yin, Ruihua; Amato, Anthony A; Ho, Doreen T; Sheikh, Sarah I; Fireman, Bruce H; Daley, Matthew F; Belongia, Edward A; Jacobsen, Steven J; Baxter, Roger; Lieu, Tracy A; Kulldorff, Martin; Vellozzi, Claudia; Lee, Grace M

    2012-06-01

    An increased risk of Guillain-Barré syndrome (GBS) following administration of the 1976 swine influenza vaccine led to a heightened focus on GBS when monovalent vaccines against a novel influenza A (H1N1) virus of swine origin were introduced in 2009. GBS cases following receipt of monovalent inactivated (MIV) and seasonal trivalent inactivated (TIV) influenza vaccines in the Vaccine Safety Datalink Project in 2009-2010 were identified in electronic data and confirmed by medical record review. Within 1-42 days following vaccination, 9 cases were confirmed in MIV recipients (1.48 million doses), and 8 cases were confirmed in TIV-only recipients who did not also receive MIV during 2009-2010 (1.72 million doses). Five cases following MIV and 1 case following TIV-only had an antecedent respiratory infection, a known GBS risk factor; furthermore, unlike TIV, MIV administration was concurrent with heightened influenza activity. In a self-controlled risk interval analysis comparing GBS onset within 1-42 days following MIV with GBS onset 43-127 days following MIV, the risk difference was 5.0 cases per million doses (95% confidence interval: 0.5, 9.5). No statistically significant increased GBS risk was found within 1-42 days following TIV-only vaccination versus 43-84 days following vaccination (risk difference = 1.1 cases per million doses, 95% confidence interval: -3.1, 5.4). Further evaluation to assess GBS risk following both vaccination and respiratory infection is warranted.

  17. [Influenza pandemic (H1N1) 2009].

    PubMed

    Oshitani, Hitoshi

    2009-12-01

    In the past, influenza pandemics have been occurring every 20 to 30 years. Highly pathogenic avian influenza A(H5N1) has been causing unprecedented global outbreaks since 2003 and many human cases with a high case fatality rate have also been reported. But the virus that caused a pandemic in 2009 was A(H1N1) that was originated from swine influenza. The same subtype, A(H1N1) has been circulating in human population since 1977. This pandemic (H1N1) 2009 is also not as virulent as A(H5N1) in humans. Many aspects of pandemic (H1N1) 2009 are different from what we had been expecting. We should reconsider the concepts and the strategies for influenza pandemic by reviewing current pandemic (H1N1).

  18. 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.

  19. The 2009 H1N1 Pandemic Influenza in Korea

    PubMed Central

    2016-01-01

    In late March of 2009, an outbreak of influenza in Mexico, was eventually identified as H1N1 influenza A. In June 2009, the World Health Organization raised a pandemic alert to the highest level. More than 214 countries have reported confirmed cases of pandemic H1N1 influenza A. In Korea, the first case of pandemic influenza A/H1N1 infection was reported on May 2, 2009. Between May 2009 and August 2010, 750,000 cases of pandemic influenza A/H1N1 were confirmed by laboratory test. The H1N1-related death toll was estimated to reach 252 individuals. Almost one billion cases of influenza occurs globally every year, resulting in 300,000 to 500,000 deaths. Influenza vaccination induces virus-neutralizing antibodies, mainly against hemagglutinin, which provide protection from invading virus. New quadrivalent inactivated influenza vaccine generates similar immune responses against the three influenza strains contained in two types of trivalent vaccines and superior responses against the additional B strain. PMID:27066083

  20. Exploring Communication, Trust in Government, and Vaccination Intention Later in the 2009 H1N1 Pandemic: Results of a National Survey

    PubMed Central

    Parmer, John; Freimuth, Vicki S.; Hilyard, Karen M.; Musa, Donald; Kim, Kevin H.

    2013-01-01

    With the growing recognition of the critical role that risk communication plays in a public health emergency, a number of articles have provided prescriptive best practices to enhance such communication. However, little empirical research has examined perceptions of the quality of communication, the impact of uncertainty on changing communication, use of information sources, and trust in specific government spokespersons. Similarly, although there is significant conceptual focus on trust and communication as important in vaccination intent and acceptance, little research has explored these relationships empirically. We conducted an online survey in late January 2010 with a nationally representative sample (N=2,079) that included Hispanic and African American oversamples. The completion rate was 56%. We found that public health officials were the most trusted spokespersons, with President Obama being the most highly trusted elected official. Demographic variables, including race, accounted for 21% of the variance in trust of the president. Perceptions of the quality of communication were high, including significant understanding of uncertainty and appreciation for officials' openness about evolving information. Other factors that contributed to vaccination acceptance were quality of communication, closely following the news, and confidence in the vaccine because of a role model effect of the Obama daughters' immunizations; these factors significantly increased trust in government actions. Because the challenges of communication often vary over the course of a pandemic, there is a consistent need to pay close attention to both communication content and delivery and prepare public health officials at all levels to be effective communicators. PMID:23617721

  1. Exploring communication, trust in government, and vaccination intention later in the 2009 H1N1 pandemic: results of a national survey.

    PubMed

    Quinn, Sandra Crouse; Parmer, John; Freimuth, Vicki S; Hilyard, Karen M; Musa, Donald; Kim, Kevin H

    2013-06-01

    With the growing recognition of the critical role that risk communication plays in a public health emergency, a number of articles have provided prescriptive best practices to enhance such communication. However, little empirical research has examined perceptions of the quality of communication, the impact of uncertainty on changing communication, use of information sources, and trust in specific government spokespersons. Similarly, although there is significant conceptual focus on trust and communication as important in vaccination intent and acceptance, little research has explored these relationships empirically. We conducted an online survey in late January 2010 with a nationally representative sample (N=2,079) that included Hispanic and African American oversamples. The completion rate was 56%. We found that public health officials were the most trusted spokespersons, with President Obama being the most highly trusted elected official. Demographic variables, including race, accounted for 21% of the variance in trust of the president. Perceptions of the quality of communication were high, including significant understanding of uncertainty and appreciation for officials' openness about evolving information. Other factors that contributed to vaccination acceptance were quality of communication, closely following the news, and confidence in the vaccine because of a role model effect of the Obama daughters' immunizations; these factors significantly increased trust in government actions. Because the challenges of communication often vary over the course of a pandemic, there is a consistent need to pay close attention to both communication content and delivery and prepare public health officials at all levels to be effective communicators.

  2. 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

  3. Moderate influenza vaccine effectiveness against hospitalisation with A(H3N2) and A(H1N1) influenza in 2013–14: Results from the InNHOVE network

    PubMed Central

    Rondy, M.; Castilla, J.; Launay, O.; Costanzo, S.; Ezpeleta, C.; Galtier, F.; de Gaetano Donati, K.; Moren, A.

    2016-01-01

    ABSTRACT We conducted a multicentre test negative case control study to estimate the 2013–14 influenza vaccine effectiveness (IVE) against hospitalised laboratory confirmed influenza in 12 hospitals in France, Italy and Spain. We included all ≥18 years hospitalised patients targeted by local influenza vaccination campaign reporting an influenza-like illness within 7 days before admission. We defined as cases patients RT-PCR positive for influenza and as controls those negative for all influenza virus. We used a logistic regression to calculate IVE adjusted for country, month of onset, chronic diseases and age. We included 104 A(H1N1)pdm09, 157 A(H3N2) cases and 585 controls. The adjusted IVE was 42.8% (95%CI: 6.3;65;0) against A(H1N1)pdm09. It was respectively 61.4% (95%CI: −1.9;85.4), 39.4% (95%CI: −32.2;72.2) and 19.7% (95%CI:-148.1;74.0) among patients aged 18–64, 65–79 and ≥80 years. The adjusted IVE against A(H3N2) was 38.1% (95%CI: 8.3;58.2) overall. It was respectively 7.8% (95%CI: −145.3;65.4), 25.6% (95%CI: −36.0;59.2) and 55.2% (95%CI: 15.4;76.3) among patients aged 18–64, 65–79 and ≥80 years. These results suggest a moderate and age varying effectiveness of the 2013–14 influenza vaccine to prevent hospitalised laboratory-confirmed influenza. While vaccination remains the most effective prevention measure, developing more immunogenic influenza vaccines is needed to prevent severe outcomes among target groups. PMID:27065000

  4. Two types of antibodies are induced by vaccination with A/California/2009 pdm virus: binding near the sialic acid-binding pocket and neutralizing both H1N1 and H5N1 viruses.

    PubMed

    Ohshima, Nobuko; Kubota-Koketsu, Ritsuko; Iba, Yoshitaka; Okuno, Yoshinobu; Kurosawa, Yoshikazu

    2014-01-01

    Many people have a history of catching the flu several times during childhood but no additional flu in adulthood, even without vaccination. We analyzed the total repertoire of antibodies (Abs) against influenza A group 1 viruses induced in such a flu-resistant person after vaccination with 2009 H1N1 pandemic influenza virus. They were classified into two types, with no exceptions. The first type, the products of B cells newly induced through vaccination, binds near the sialic acid-binding pocket. The second type, the products of long-lived memory B cells established before vaccination, utilizes the 1-69 VH gene, binds to the stem of HA, and neutralizes both H1N1 and H5N1 viruses with few exceptions. These observations indicate that the sialic acid-binding pocket and its surrounding region are immunogenically very potent and majority of the B cells whose growth is newly induced by vaccination produce Abs that recognize these regions. However, they play a role in protection against influenza virus infection for a short period since variant viruses that have acquired resistance to these Abs become dominant. On the other hand, although the stem of HA is immunogenically not potent, the second type of B cells eventually becomes dominant. Thus, a selection system should function in forming the repertoire of long-lived memory B cells and the stability of the epitope would greatly affect the fate of the memory cells. Acquisition of the ability to produce Abs that bind to the stable epitope could be a major factor of flu resistance.

  5. Changes in and shortcomings of control strategies, drug stockpiles, and vaccine development during outbreaks of avian influenza A H5N1, H1N1, and H7N9 among humans.

    PubMed

    Mei, Lin; Song, Peipei; Tang, Qi; Shan, Ke; Tobe, Ruoyan Gai; Selotlegeng, Lesego; Ali, Asghar Hammad; Cheng, Yangyang; Xu, Lingzhong

    2013-04-01

    The purpose of this review is to provide a reference for the future prevention and control of emerging infectious diseases by summarizing the control strategies, the status of drugs and vaccines, and shortcomings during three major outbreaks of avian influenza among humans (H5N1 in 2003, H1N1 in 2009, and H7N9 in 2013). Data on and documents regarding the three influenza outbreaks have been reviewed. Results indicated that the response to pandemic influenza outbreaks has improved markedly in terms of control strategies, stockpiles of antivirals, and vaccine development. These improvements also suggest advances in disease surveillance, transparency in reporting, and regional collaboration and cooperation. These trends also foreshadow better prospects for prevention and control of emerging infectious diseases. However, there are shortcomings since strategies failed to focus on high-risk groups, quantitative and measurable results (both direct and indirect) were unclear, and quantitative assessment is still lacking.

  6. Supplementation of H1N1pdm09 split vaccine with heterologous tandem repeat M2e5x virus-like particles confers improved cross-protection in ferrets

    PubMed Central

    Music, Nedzad; Reber, Adrian J.; Kim, Min-Chul; York, Ian A.; Kang, Sang-Moo

    2015-01-01

    Current influenza vaccines induce strain-specific immunity to the highly variable hemagglutinin (HA) protein. It is therefore a high priority to develop vaccines that induce broadly cross-protective immunity to different strains of influenza. Since influenza A M2 proteins are highly conserved among different strains, five tandem repeats of the extracellular peptide of M2 in a membrane-anchored form on virus-like particles (VLPs) have been suggested to be a promising candidate for universal influenza vaccine. In this study, ferrets were intramuscularly immunized with 2009 H1N1 split HA vaccine (“Split”) alone, influenza split vaccine supplemented with M2e5x VLP (“Split+M2e5x”), M2e5x VLP alone (“M2e5x”), or mock immunized. Vaccine efficacy was measured serologically and by protection against a serologically distinct viral challenge. Ferrets immunized with Split+M2e5x induced HA strain specific and conserved M2e immunity. Supplementation of M2e5x VLP to split vaccination significantly increased the immunogenicity of split vaccine compared to split alone. The Split+M2e5x ferret group showed evidence of cross-reactive protection, including faster recovery from weight loss, and reduced inflammation, as inferred from changes in peripheral leukocyte subsets, compared to mock-immunized animals. In addition, ferrets immunized with Split+M2e5x shed lower viral nasal-wash titers than the other groups. Ferrets immunized with M2e5x alone also show some protective effects, while those immunized with split vaccine alone induced no protective effects compared to mock-immunized ferrets. These studies suggest that supplementation of split vaccine with M2e5x-VLP may provide broader and improved cross-protection than split vaccine alone. PMID:26709639

  7. A novel bivalent vaccine based on a PB2-knockout influenza virus protects mice from pandemic H1N1 and highly pathogenic H5N1 virus challenges.

    PubMed

    Uraki, Ryuta; Kiso, Maki; Iwatsuki-Horimoto, Kiyoko; Fukuyama, Satoshi; Takashita, Emi; Ozawa, Makoto; Kawaoka, Yoshihiro

    2013-07-01

    Vaccination is an effective means to protect against influenza virus. Although inactivated and live-attenuated vaccines are currently available, each vaccine has disadvantages (e.g., immunogenicity and safety issues). To overcome these problems, we previously developed a replication-incompetent PB2-knockout (PB2-KO) influenza virus that replicates only in PB2 protein-expressing cells. Here, we generated two PB2-KO viruses whose PB2-coding regions were replaced with the HA genes of either A/California/04/2009 (H1N1pdm09) or A/Vietnam/1203/2004 (H5N1). The resultant viruses comparably, or in some cases more efficiently, induced virus-specific antibodies in the serum, nasal wash, and bronchoalveolar lavage fluid of mice relative to a conventional formalin-inactivated vaccine. Furthermore, mice immunized with these PB2-KO viruses were protected from lethal challenges with not only the backbone virus strain but also strains from which their foreign HAs originated, indicating that PB2-KO viruses with antigenically different HAs could serve as bivalent influenza vaccines.

  8. H1N1 Preparedness and Recent Lessons Learned

    DTIC Science & Technology

    2011-01-25

    elderly, no change in virulence, no significant genetic drift 2011 MHS Conference 2009 H1N1  Sensitive to Oseltamivir & Zanamivir – Rare... Oseltamivir resistance identified ~ 1%  No protection from seasonal influenza vaccine per CDC but – DoD data suggests vaccine effectiveness up to 50% for... Oseltamivir represented bulk of DoD stockpile – 8M treatment courses • 1M @ MTFs • 7M @ Depots  Funding received for – More Zanamivir - Will

  9. 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.

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

    PubMed

    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.

  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. Enhancing community partnerships during a public health emergency: the school-located vaccination clinics model in Kanawha County, WV during the 2009 influenza A (H1N1) pandemic.

    PubMed

    Gupta, Rahul

    2011-01-01

    Broad based community support is vital in developing a comprehensive national strategy to protect the public's health prior to, during and after a disaster such as pandemic influenza. When disaster strikes, the successful response is often dependent upon the degree of collaboration, coordination, and shared decision making occurring among a wide-ranging group of public and private stakeholders in the community. Since these preparedness and response activities must occur at a local level, the degree to which a certain community can become resilient after an event is directly dependent upon the success of the response activities. In order to protect its citizens, the Kanawha-Charleston Health Department (KCHD) led a comprehensive community based response to the 2009 Influenza A (H1N1) pandemic. By organizing a high level strategic team consisting of major community stakeholders, KCHD was able to develop broad based community support for its mitigation and countermeasure delivery strategies. The timely enhancement of the existing community partnerships enabled us to successfully conduct several response activities with local community support including school-located vaccination (SLV) clinics. We describe the process, results and challenges faced during our SLV clinics campaign which resulted in exceptionally high vaccination rates for school aged children compared to other jurisdictions across the nation. We also discuss how such partnerships can be sustained resulting in resilient communities and mention some strategies for those contemplating such partnerships in future public health emergency.

  13. Enhanced Pneumonia and Proinflammatory Cytokine Response in Pigs Challenged with Pandemic 2009 A/H1N1 Influenza Virus Following Vaccination with an Inactivated delta-Cluster H1N2 Virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Endemic strains of swine influenza A virus (IAV) in North America consist of the subtypes H1N1, H1N2, and H3N2. These circulating strains contain the triple reassortant internal gene (TRIG) cassette resulting from incorporation of genes from swine, avian, and human IAV’s. Genetic drift and reassortm...

  14. A dose-ranging study of MF59®-adjuvanted and non-adjuvanted A/H1N1 pandemic influenza vaccine in young to middle-aged and older adult populations to assess safety, immunogenicity, and antibody persistence one year after vaccination

    PubMed Central

    Reisinger, Keith S; Holmes, Sandra J; Pedotti, Paola; Arora, Ashwani Kumar; Lattanzi, Maria

    2014-01-01

    Background During development of an A/H1N1 pandemic influenza vaccine, this study was performed to identify the antigen and adjuvant content which would provide optimal antibody response and persistence in adults and the elderly. Dose-sparing strategies, such as inclusion of adjuvants, are critical in ensuring the widest possible population coverage in the event of an influenza pandemic, despite a limited global capacity for vaccine manufacture. Methods Healthy subjects aged 18−64 years (n = 1240) and ≥65 years (n = 1352) were vaccinated with 1 of 8 investigational vaccine formulations varying in antigen quantity (3.75 µg to 30 µg of hemagglutinin) and MF59® adjuvant (none, half dose, or full dose). All subjects received 2 vaccine doses administered 3 weeks apart. Antibody response was assessed by hemagglutination inhibition assay 1 and 3 weeks after administration of first and second doses. Antibody persistence was assessed after 6 and 12 mo. Vaccine safety was monitored over 12 mo. Results All 8 investigational A/H1N1 vaccine formulations were well tolerated, and rapidly induced high antibody titers which met all of the Center for Biologics Evaluation and Research (CBER) and Committee for Medicinal Products for Human Use (CHMP) licensure criteria 3 weeks after one dose. The highest antibody titers were observed in participants vaccinated with higher quantities of antigen and adjuvant. Conclusion A single vaccine dose containing 3.75 µg of A/California/7/2009 (H1N1) antigen with MF59 adjuvant was identified as optimal for young to middle-aged (18−64 years) and older (≥65 years) adult populations. PMID:25424947

  15. Host Modulators of H1N1 Cytopathogenicity

    PubMed Central

    Ward, Samuel E.; Kim, Hyun Seok; Komurov, Kakajan; Mendiratta, Saurabh; Tsai, Pei-Ling; Schmolke, Mirco; Satterly, Neal; Manicassamy, Balaji; Forst, Christian V.; Roth, Michael G.; García-Sastre, Adolfo; Blazewska, Katarzyna M.; McKenna, Charles E.; Fontoura, Beatriz M.; White, Michael A.

    2012-01-01

    Influenza A virus infects 5–20% of the population annually, resulting in ∼35,000 deaths and significant morbidity. Current treatments include vaccines and drugs that target viral proteins. However, both of these approaches have limitations, as vaccines require yearly development and the rapid evolution of viral proteins gives rise to drug resistance. In consequence additional intervention strategies, that target host factors required for the viral life cycle, are under investigation. Here we employed arrayed whole-genome siRNA screening strategies to identify cell-autonomous molecular components that are subverted to support H1N1 influenza A virus infection of human bronchial epithelial cells. Integration across relevant public data sets exposed druggable gene products required for epithelial cell infection or required for viral proteins to deflect host cell suicide checkpoint activation. Pharmacological inhibition of representative targets, RGGT and CHEK1, resulted in significant protection against infection of human epithelial cells by the A/WS/33 virus. In addition, chemical inhibition of RGGT partially protected against H5N1 and the 2009 H1N1 pandemic strain. The observations reported here thus contribute to an expanding body of studies directed at decoding vulnerabilities in the command and control networks specified by influenza virulence factors. PMID:22876275

  16. H1N1 Flu (Swine Flu)

    MedlinePlus

    ... prevent or treat swine flu. There is a vaccine available to protect against swine flu. You can help prevent the spread of germs that cause respiratory illnesses like influenza by Covering your nose and mouth with a ...

  17. 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.

  18. 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

  19. Pandemic H1N1 influenza A directly induces a robust and acute inflammatory gene signature in primary human bronchial epithelial cells downstream of membrane fusion

    SciTech Connect

    Paquette, Stéphane G.; Banner, David; Chi, Le Thi Bao; Leon, Alberto J.; Xu, Luoling; Ran, Longsi; Huang, Stephen S.H.; Farooqui, Amber; and others

    2014-01-05

    Pandemic H1N1 influenza A (H1N1pdm) elicits stronger pulmonary inflammation than previously circulating seasonal H1N1 influenza A (sH1N1), yet mechanisms of inflammatory activation in respiratory epithelial cells during H1N1pdm infection are unclear. We investigated host responses to H1N1pdm/sH1N1 infection and virus entry mechanisms in primary human bronchial epithelial cells in vitro. H1N1pdm infection rapidly initiated a robust inflammatory gene signature (3 h post-infection) not elicited by sH1N1 infection. Protein secretion inhibition had no effect on gene induction. Infection with membrane fusion deficient H1N1pdm failed to induce robust inflammatory gene expression which was rescued with restoration of fusion ability, suggesting H1N1pdm directly triggered the inflammatory signature downstream of membrane fusion. Investigation of intra-virion components revealed H1N1pdm viral RNA (vRNA) triggered a stronger inflammatory phenotype than sH1N1 vRNA. Thus, our study is first to report H1N1pdm induces greater inflammatory gene expression than sH1N1 in vitro due to direct virus–epithelial cell interaction. - Highlights: • We investigated H1N1pdm/sH1N1 infection in primary epithelial cells. • H1N1pdm directly initiated a robust inflammatory gene signature, sH1N1 did not. • H1N1pdm viral RNA triggered a stronger response than sH1N1. • H1N1pdm induces greater response due to direct virus–cell interaction. • These results have potential to impact vaccine and therapeutic development.

  20. 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

  1. Differential influenza H1N1-specific humoral and cellular response kinetics in kidney transplant patients.

    PubMed

    Rambal, Vinay; Müller, Karin; Dang-Heine, Chantip; Sattler, Arne; Dziubianau, Mikalai; Weist, Benjamin; Luu, Si-Hong; Stoyanova, Alexandra; Nickel, Peter; Thiel, Andreas; Neumann, Avidan; Schweiger, Brunhilde; Reinke, Petra; Babel, Nina

    2014-02-01

    Renal transplant recipients (RTR) are considered at high risk for influenza-associated complications due to immunosuppression. The efficacy of standard influenza vaccination in RTRs is unclear. Hence, we evaluated activation of the adaptive immunity by the pandemic influenza A(H1N1) 2009 (A(H1N1)pdm09) vaccine in RTRs as compared to healthy controls. To determine cross-reactivity and/or bystander activation, seasonal trivalent influenza vaccine and tetanus/diphteria toxoid (TT/DT) vaccine-specific T cells along with allospecific T cells were quantified before and after A(H1N1)pdm09 vaccination. Vaccination-induced alloimmunity was additionally determined by quantifying serum creatinine and proinflammatory protein IP-10. Contrary to healthy controls, RTRs required a booster vaccination to achieve seroconversion (13.3 % day 21; 90 % day 90). In contrast to humoral immunity, sufficient A(H1N1)pdm09-specific T-cell responses were mounted in RTRs already after the first immunization with a magnitude comparable with healthy controls. Interestingly, vaccination simultaneously boosted T cells reacting to seasonal flu but not to TT/DT, suggesting cross-activation. No alloimmune effects were recorded. In conclusion, protective antibody responses required booster vaccination. However, sufficient cellular immunity is established already after the first vaccination, demonstrating differential kinetics of humoral and cellular immunity.

  2. 2009 Pandemic Influenza A (H1N1): Diagnosis, Management, and Prevention- Lessons Learned.

    PubMed

    Swedish, Kristin A

    2011-04-01

    The 2009 pandemic influenza A (H1N1) was responsible for the first influenza pandemic of the 21st century. The virus- a previously unknown triple-reassortant virus containing segments of avian, human, and swine origins- generally caused mild disease. Unlike seasonal influenza, 2009 pandemic influenza A (H1N1) primarily affected adults 18 to 64 years of age. During the course of the pandemic, public health officials tried to facilitate diagnostic procedures and share information about treatment modalities globally. Efforts to contain the spread of 2009 pandemic influenza A (H1N1) included personal protective mechanisms and the 2009 H1N1 vaccine, which was not produced quickly enough or in large enough quantities. The lessons learned from this pandemic should be applied to ensure better preparedness in case of future pandemics.

  3. Symmetric Peripheral Gangrene Associated with H1N1 Infection

    PubMed Central

    Kaulgud, Ram S.; Kamath, Vasantha; Patil, Vijayalaxmi; Desai, Sagar

    2013-01-01

    More and more cases of H1N1 influenza are being detected in India and so also the variety of complications this virus can cause. Here, we report a case of symmetric peripheral gangrene following H1N1 infection. PMID:24319562

  4. Seroprevalence following the first wave of pandemic influenza A (H1N1) in Turkey, 2009.

    PubMed

    Gözalan, Ayşegül; Altaş, Ayşe Başak; Sevencan, Funda; Akın, Levent; Korukluoğlu, Gülay; Kara, Sükran; Sevindi, Demet Furkan; Ertek, Mustafa

    2012-01-01

    In this study, we sought to describe the community seropositivity of pandemic influenza A (H1N1) in order to estimate immunity shortly after the peak of the first pandemic wave in two provinces in Turkey. This cross-sectional study was conducted in the provinces of Diyarbakir and Ankara, after the first wave of H1N1 incidences in 2009. It was designed to evaluate 276 houses in Diyarbakir and 455 houses in Ankara. Everyone living in these houses was included in the study. An antibody titer of ≥1:40 was considered as a positive result for all age groups. Antibody titers of ≤1:20 were considered as 1 while calculating the log titer and geometric mean. The pandemic H1N1 seropositivity was found to be 24.1% for Ankara and 27.7% for Diyarbakir. In Ankara, seropositivity was statistically associated with the 15-24 age group (odds ratio [OR] = 11.47), pandemic influenza A (H1N1) vaccination (OR = 20.95), and influenza-like illness history (OR = 1.60). In Diyarbakir, H1N1 seropositivity was associated with the 15-24 age group (OR = 8.99) and pandemic influenza A (H1N1) vaccination (OR = 9.94). Because individuals less than 25 years old played an important role in the community transmission of infection and were largely protected against the pandemic influenza A (H1N1) virus, these individuals should be given a high priority for pandemic influenza vaccination in the event of the emergence of another novel pandemic strain.

  5. H1N1pdm in the Americas.

    PubMed

    Lessler, Justin; dos Santos, Thais; Aguilera, Ximena; Brookmeyer, Ron; Cummings, Derek A T

    2010-09-01

    In late April 2009 the emergence of 2009 pandemic influenza A (H1N1pdm) virus was detected in humans. From its detection through July 18th, 2009, confirmed cases of H1N1pdm in the Americas were periodically reported to the Pan American Health Organization (PAHO) by member states. Because the Americas span much of the world's latitudes, this data provides an excellent opportunity to examine variation in H1N1pdm transmission by season. Using reports from PAHO member states from April 26th, 2009 through July 18th, 2009, we characterize the early spread of the H1N1 pandemic in the Americas. For a geographically representative sample of member states we estimate the reproductive number (R) of H1N1pdm over the reporting period. The association between these estimates and latitude, temperature, humidity and population age structure was estimated. Estimates of the peak reproductive number of H1N1pdm ranged from 1.3 (for Panama, Colombia) to 2.1 (for Chile). We found that reproductive number estimates were most associated with latitude in both univariate and multivariate analyses. To the extent that latitude is a proxy for seasonal changes in climate and behavior, this association suggests a strong seasonal component to H1N1pdm transmission. However, the reasons for this seasonality remain unclear.

  6. Swine influenza H1N1 virus induces acute inflammatory immune responses in pig lungs: a potential animal model for human H1N1 influenza virus.

    PubMed

    Khatri, Mahesh; Dwivedi, Varun; Krakowka, Steven; Manickam, Cordelia; Ali, Ahmed; Wang, Leyi; Qin, Zhuoming; Renukaradhya, Gourapura J; Lee, Chang-Won

    2010-11-01

    Pigs are capable of generating reassortant influenza viruses of pandemic potential, as both the avian and mammalian influenza viruses can infect pig epithelial cells in the respiratory tract. The source of the current influenza pandemic is H1N1 influenza A virus, possibly of swine origin. This study was conducted to understand better the pathogenesis of H1N1 influenza virus and associated host mucosal immune responses during acute infection in humans. Therefore, we chose a H1N1 swine influenza virus, Sw/OH/24366/07 (SwIV), which has a history of transmission to humans. Clinically, inoculated pigs had nasal discharge and fever and shed virus through nasal secretions. Like pandemic H1N1, SwIV also replicated extensively in both the upper and lower respiratory tracts, and lung lesions were typical of H1N1 infection. We detected innate, proinflammatory, Th1, Th2, and Th3 cytokines, as well as SwIV-specific IgA antibody in lungs of the virus-inoculated pigs. Production of IFN-γ by lymphocytes of the tracheobronchial lymph nodes was also detected. Higher frequencies of cytotoxic T lymphocytes, γδ T cells, dendritic cells, activated T cells, and CD4+ and CD8+ T cells were detected in SwIV-infected pig lungs. Concomitantly, higher frequencies of the immunosuppressive T regulatory cells were also detected in the virus-infected pig lungs. The findings of this study have relevance to pathogenesis of the pandemic H1N1 influenza virus in humans; thus, pigs may serve as a useful animal model to design and test effective mucosal vaccines and therapeutics against influenza virus.

  7. North American Triple Reassortant and Eurasian H1N1 Swine Influenza Viruses Do Not Readily Reassort to Generate a 2009 Pandemic H1N1-Like Virus

    PubMed Central

    Ma, Wenjun; Liu, Qinfang; Qiao, Chuanling; del Real, Gustavo; García-Sastre, Adolfo; Webby, Richard J.; Richt, Jürgen A.

    2014-01-01

    ABSTRACT 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. PMID:24618255

  8. 'Rhyme or reason?' Saying no to mass vaccination: subjective re-interpretation in the context of the A(H1N1) influenza pandemic in Sweden 2009-2010.

    PubMed

    Lundgren, Britta

    2015-12-01

    During the swine flu pandemic of 2009-2010, all Swedish citizens were recommended to be vaccinated with the influenza vaccine Pandemrix. However, a very serious and unexpected side effect emerged during the summer of 2010: more than 200 children and young adults were diagnosed with narcolepsy after vaccination. Besides the tragic outcome for these children and their families, this adverse side effect suggests future difficulties in obtaining trust in vaccination in cases of emerging pandemics, and thus there is a growing need to find ways to understand the complexities of vaccination decision processes. This article explores written responses to a questionnaire from a Swedish folk life archive as an unconventional source for analysing vaccine decisions. The aim is to investigate how laypersons responded to and re-interpreted the message about the recommended vaccination in their answers. The answers show the confusion and complex circumstances and influences in everyday life that people reflect on when making such important decisions. The issue of confusion is traced back to the initial communications about the vaccination intervention in which both autonomy and solidarity were expected from the population. Common narratives and stories about the media or 'big pharma capitalism' are entangled with private memories, accidental coincidences and serendipitous associations. It is obvious that vaccination interventions that require compliance from large groups of people need to take into account the kind of personal experience narratives that are produced by the complex interplay of the factors described by the informants.

  9. ‘Rhyme or reason?’ Saying no to mass vaccination: subjective re-interpretation in the context of the A(H1N1) influenza pandemic in Sweden 2009–2010

    PubMed Central

    Lundgren, Britta

    2015-01-01

    During the swine flu pandemic of 2009–2010, all Swedish citizens were recommended to be vaccinated with the influenza vaccine Pandemrix. However, a very serious and unexpected side effect emerged during the summer of 2010: more than 200 children and young adults were diagnosed with narcolepsy after vaccination. Besides the tragic outcome for these children and their families, this adverse side effect suggests future difficulties in obtaining trust in vaccination in cases of emerging pandemics, and thus there is a growing need to find ways to understand the complexities of vaccination decision processes. This article explores written responses to a questionnaire from a Swedish folk life archive as an unconventional source for analysing vaccine decisions. The aim is to investigate how laypersons responded to and re-interpreted the message about the recommended vaccination in their answers. The answers show the confusion and complex circumstances and influences in everyday life that people reflect on when making such important decisions. The issue of confusion is traced back to the initial communications about the vaccination intervention in which both autonomy and solidarity were expected from the population. Common narratives and stories about the media or ‘big pharma capitalism’ are entangled with private memories, accidental coincidences and serendipitous associations. It is obvious that vaccination interventions that require compliance from large groups of people need to take into account the kind of personal experience narratives that are produced by the complex interplay of the factors described by the informants. PMID:26077985

  10. A Set of Novel Monoclonal Antibodies Against Swine-Origin Pandemic H1N1 Differentiate Swine H1N1 and Human Seasonal H1N1

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In April 2009, a novel H1N1 influenza virus (S-OIV) emerged in North America and caused the first influenza pandemic of the 21st century. The new pandemic strain is a triple reassortant influenza virus of swine origin containing genes from avian, swine and human influenza viruses. It is genetically ...

  11. Modeling control strategies for concurrent epidemics of seasonal and pandemic H1N1 influenza.

    PubMed

    Prosper, Olivia; Saucedo, Omar; Thompson, Doria; Torres-Garcia, Griselle; Wang, Xiaohong; Castillo-Chavez, Carlos

    2011-01-01

    The lessons learned from the 2009-2010 H1N1 influenza pandemic, as it moves out of the limelight, should not be under-estimated, particularly since the probability of novel influenza epidemics in the near future is not negligible and the potential consequences might be huge. Hence, as the world, particularly the industrialized world, responded to the potentially devastating effects of this novel A-H1N1 strain with substantial resources, reminders of the recurrent loss of life from a well established foe, seasonal influenza, could not be ignored. The uncertainties associated with the reported and expected levels of morbidity and mortality with this novel A-H1N1 live in a backdrop of deaths, over 200,000 hospitalizations, and millions of infections (20% of the population) attributed to seasonal influenza in the USA alone, each year. So, as the Northern Hemisphere braced for the possibility of a potentially "lethal" second wave of the novel A-H1N1 without a vaccine ready to mitigate its impact, questions of who should be vaccinated first if a vaccine became available, came to the forefront of the discussion. Uncertainty grew as we learned that the vaccine, once available, would be unevenly distributed around the world. Nations capable of acquiring large vaccine supplies soon became aware that those who could pay would have to compete for a limited vaccine stockpile. The challenges faced by nations dealing jointly with seasonal and novel A-H1N1 co-circulating strains under limited resources, that is, those with no access to novel A-H1N1 vaccine supplies, limited access to the seasonal influenza vaccine, and limited access to antivirals (like Tamiflu) are explored in this study. One- and two-strain models are introduced to mimic the influenza dynamics of a single and co-circulating strains, in the context of a single epidemic outbreak. Optimal control theory is used to identify and evaluate the "best" control policies. The controls account for the cost associated with

  12. Classical swine H1N1 influenza viruses confer cross protection from swine-origin 2009 pandemic H1N1 influenza virus infection in mice and ferrets.

    PubMed

    Min, Ji-Young; Chen, Grace L; Santos, Celia; Lamirande, Elaine W; Matsuoka, Yumiko; Subbarao, Kanta

    2010-12-05

    The hemagglutinin of the 2009 pandemic H1N1 influenza virus is a derivative of and is antigenically related to classical swine but not to seasonal human H1N1 viruses. We compared the A/California/7/2009 (CA/7/09) virus recommended by the WHO as the reference virus for vaccine development, with two classical swine influenza viruses A/swine/Iowa/31 (sw/IA/31) and A/New Jersey/8/1976 (NJ/76) to establish the extent of immunologic cross-reactivity and cross-protection in animal models. Primary infection with 2009 pandemic or NJ/76 viruses elicited antibodies against the CA/7/09 virus and provided complete protection from challenge with this virus in ferrets; the response in mice was variable and conferred partial protection. Although ferrets infected with sw/IA/31 virus developed low titers of cross-neutralizing antibody, they were protected from pulmonary replication of the CA/7/09 virus. The data suggest that prior exposure to antigenically related H1N1 viruses of swine-origin provide some protective immunity against the 2009 pandemic H1N1 virus.

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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. Vaccine effectiveness in preventing laboratory-confirmed influenza in primary care patients in a season of co-circulation of influenza A(H1N1)pdm09, B and drifted A(H3N2), I-MOVE Multicentre Case-Control Study, Europe 2014/15.

    PubMed

    Valenciano, Marta; Kissling, Esther; Reuss, Annicka; Rizzo, Caterina; Gherasim, Alin; Horváth, Judit Krisztina; Domegan, Lisa; Pitigoi, Daniela; Machado, Ausenda; Paradowska-Stankiewicz, Iwona Anna; Bella, Antonino; Larrauri, Amparo; Ferenczi, Annamária; Lazar, Mihaela; Pechirra, Pedro; Korczyńska, Monika Roberta; Pozo, Francisco; Moren, Alain

    2016-01-01

    Influenza A(H3N2), A(H1N1)pdm09 and B viruses co-circulated in Europe in 2014/15. We undertook a multicentre case-control study in eight European countries to measure 2014/15 influenza vaccine effectiveness (VE) against medically-attended influenza-like illness (ILI) laboratory-confirmed as influenza. General practitioners swabbed all or a systematic sample of ILI patients. We compared the odds of vaccination of ILI influenza positive patients to negative patients. We calculated adjusted VE by influenza type/subtype, and age group. Among 6,579 ILI patients included, 1,828 were A(H3N2), 539 A(H1N1)pdm09 and 1,038 B. VE against A(H3N2) was 14.4% (95% confidence interval (CI): -6.3 to 31.0) overall, 20.7% (95%CI: -22.3 to 48.5), 10.9% (95%CI -30.8 to 39.3) and 15.8% (95% CI: -20.2 to 41.0) among those aged 0-14, 15-59 and  ≥60  years, respectively. VE against A(H1N1)pdm09 was 54.2% (95%CI: 31.2 to 69.6) overall, 73.1% (95%CI: 39.6 to 88.1), 59.7% (95%CI: 10.9 to 81.8), and 22.4% (95%CI: -44.4 to 58.4) among those aged 0-14, 15-59 and  ≥60 years respectively. VE against B was 48.0% (95%CI: 28.9 to 61.9) overall, 62.1% (95%CI: 14.9 to 83.1), 41.4% (95%CI: 6.2 to 63.4) and 50.4% (95%CI: 14.6 to 71.2) among those aged 0-14, 15-59 and ≥60 years respectively. VE against A(H1N1)pdm09 and B was moderate. The low VE against A(H3N2) is consistent with the reported mismatch between circulating and vaccine strains.

  15. Risk factors for death from pandemic (H1N1) 2009, southern Brazil.

    PubMed

    Yokota, Renata T C; Skalinski, Lacita M; Igansi, Cristine N; de Souza, Libia R O; Iser, Betine P M; Reis, Priscilleyne O; Barros, Eliana N C; Macário, Eduardo M; Bercini, Marilina A; Ranieri, Tani M S; Araújo, Wildo N

    2011-08-01

    To identify risk factors for death from pandemic (H1N1) 2009, we obtained data for 157 hospitalized patients with confirmed cases of this disease. Multivariate analysis showed that diabetes and class III obesity were associated with death. These findings helped define priority vaccination groups in Brazil.

  16. Epidemiology and full genome sequence analysis of H1N1pdm09 from Northeast China.

    PubMed

    Li, Xiaoyan; Kong, Mei; Chen, Jinying; Su, Xu; Zou, Ming; Guo, Liru; Li, Lin; Ding, Jianqing

    2013-10-01

    Pandemic influenza A (H1N1) 2009 virus (H1N1pdm09) was a novel tri-assortment virus that emerged in Mexico and North America in 2009 and caused the first influenza pandemic in the 21st century. This study investigated the prevalence pattern and molecular characteristics of H1N1pdm09 in three continuous years from April 2009 to March 2012 in populations of Tianjin, Northeast China. Totally, 3,068 influenza viruses (25.4 %) were detected from 12,089 respiratory specimens. Among them, 41.4 % (1,269/3,068) were H1N1pdm09 positive. 15.1 % (192/1,269) severe respiratory infection cases were H1N1pdm09 positive. H1N1pdm09 was the predominant prevalence subtype in October 2009-March 2010 (69.1 %, 930/1,346) and October 2010-March 2011 (42.1 %, 220/523). Eight isolated H1N1pdm09 viruses from severe infection/death cases in three different years were selected to sequence the whole genome through splicing the sequences following 46 PCRs. HA sequences of seven H1N1pdm09 isolates from mild infection cases were detected. Phylogenetic analysis showed that HA, NA, M, NP and NS genes of H1N1pdm09 viruses gathered together with swine influenza A (H1N1), whereas PB2 and PA genes originated from avian influenza virus, and PB1 gene originated from human seasonal influenza virus. Identity analysis indicated that all the genes were highly conserved. Compared with vaccine strain A/California/07/2009(H1N1), the maximal mutation gene was HA (0.7-2.6 %), then NA (0.6-1.7 %), last one was M (mutation rate 0-0.6 %). More site substitutions were observed in 2011 isolates than in 2009 and 2010 isolates of HA (p = 0.002), NA (p = 0.003) and PA (p = 0.001) proteins. The amino acid substitution rates were varied among eight gene segments, ranging from 7.39 × 10(-4) for PB2 to 7.40 × 10(-3) for NA. The higher d N / d S rates were observed in HA, PA and NS segments in H1N1pdm09 in Tianjin. Three HA amino acid site substitutions occurred at the HA receptor-binding sites and

  17. H1N1, globalization and the epidemiology of inequality.

    PubMed

    Sparke, Matthew; Anguelov, Dimitar

    2012-07-01

    This paper examines the lessons learned from the 2009 H1N1 pandemic in relation to wider work on globalization and the epidemiology of inequality. The media attention and economic resources diverted to the threats posed by H1N1 were significant inequalities themselves when contrasted with weaker responses to more lethal threats posed by other diseases associated with global inequality. However, the multiple inequalities revealed by H1N1 itself in 2009 still provide important insights into the future of global health in the context of market-led globalization. These lessons relate to at least four main forms of inequality: (1) inequalities in blame for the outbreak in the media; (2) inequalities in risk management; (3) inequalities in access to medicines; and (4) inequalities encoded in the actual emergence of new flu viruses.

  18. Outbreaks of 2009 pandemic influenza A (H1N1) among long-term-care facility residents - three states, 2009.

    PubMed

    2010-01-29

    Hospitalization and death from seasonal influenza are more common among older adults and in long-term--care facilities (LTCFs). Early data from the 2009 pandemic influenza A (H1N1) outbreak indicated that attack rates among persons aged >or=65 years were lower than in other age groups, and anti-influenza A antibodies that cross-react with 2009 H1N1 could be detected in up to one third of healthy adults aged >60 years. Based on these early data and anticipation of limited initial supplies of 2009 H1N1 vaccine, the Advisory Committee on Immunization Practices (ACIP) identified priority groups for vaccination, which did not include persons aged >or=65 years who did not have higher risk for influenza or its complications. During October and November 2009, CDC received reports of 2009 H1N1 outbreaks in LTCFs in Colorado, Maine, and New York. This report summarizes the three outbreaks, which involved facilities primarily housing older patients. These outbreaks illustrate that, despite the lower risk for infection with 2009 H1N1 among persons aged >or=65 years compared with seasonal influenza, 2009 H1N1 outbreaks still can occur in LTCFs. These outbreaks also underscore the importance of respiratory illness surveillance and recommended infection-control procedures in LTCFs. All health-care personnel should be vaccinated against seasonal influenza and 2009 H1N1. LTCF residents should receive seasonal influenza vaccination, and should be vaccinated against 2009 H1N1 after assessment of vaccine availability at the local level indicates that demand for vaccine among younger age groups is being met.

  19. Pandemic (H1N1) 2009 in captive cheetah.

    PubMed

    Crossley, Beate; Hietala, Sharon; Hunt, Tania; Benjamin, Glenn; Martinez, Marie; Darnell, Daniel; Rubrum, Adam; Webby, Richard

    2012-02-01

    We describe virus isolation, full genome sequence analysis, and clinical pathology in ferrets experimentally inoculated with pandemic (H1N1) 2009 virus recovered from a clinically ill captive cheetah that had minimal human contact. Evidence of reverse zoonotic transmission by fomites underscores the substantial animal and human health implications of this virus.

  20. 2009 H1N1 fatalities: the New Mexico experience.

    PubMed

    Brooks, Erin G; Bryce, Clare H; Avery, Catherine; Smelser, Chad; Thompson, Deborah; Nolte, Kurt B

    2012-11-01

    Histopathologic features of New Mexico 2009 H1N1 fatalities have not been representative of those reported nationwide. We retrospectively reviewed medical records of all New Mexico 2009 pandemic influenza A (pH1N1) fatalities (n = 50). In cases in which autopsy was performed (n = 12), histologic sections and culture results were examined. In contrast to previously published studies, the majority of our fatalities did not have diffuse alveolar damage (DAD) (2/12; 16.7%). Common findings included pulmonary interstitial inflammation and edema, tracheobronchitis, and pneumonia. Two cases had significant extra-pulmonary manifestations: myocarditis and cerebral edema with herniation. The majority had a rapid disease course: range from 1 to 12 days (median, 2 days), and Native Americans were disproportionately represented among fatalities. These findings suggest that New Mexico H1N1 fatalities generally did not survive long enough to develop the classic picture of DAD. Pathologists should be aware that H1N1 may cause extra-pulmonary pathology and perform postmortem cultures and histologic sampling accordingly.

  1. 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.

  2. Detection of Extensive Cross-Neutralization between Pandemic and Seasonal A/H1N1 Influenza Viruses Using a Pseudotype Neutralization Assay

    PubMed Central

    Labrosse, Béatrice; Tourdjman, Mathieu; Porcher, Raphaël; LeGoff, Jérôme; de Lamballerie, Xavier; Simon, François; Molina, Jean-Michel; Clavel, François

    2010-01-01

    Background Cross-immunity between seasonal and pandemic A/H1N1 influenza viruses remains uncertain. In particular, the extent that previous infection or vaccination by seasonal A/H1N1 viruses can elicit protective immunity against pandemic A/H1N1 is unclear. Methodology/Principal Findings Neutralizing titers against seasonal A/H1N1 (A/Brisbane/59/2007) and against pandemic A/H1N1 (A/California/04/2009) were measured using an HIV-1-based pseudovirus neutralization assay. Using this highly sensitive assay, we found that a large fraction of subjects who had never been exposed to pandemic A/H1N1 express high levels of pandemic A/H1N1 neutralizing titers. A significant correlation was seen between neutralization of pandemic A/H1N1 and neutralization of a standard seasonal A/H1N1 strain. Significantly higher pandemic A/H1N1 neutralizing titers were measured in subjects who had received vaccination against seasonal influenza in 2008–2009. Higher pandemic neutralizing titers were also measured in subjects over 60 years of age. Conclusions/Significance Our findings reveal that the extent of protective cross-immunity between seasonal and pandemic A/H1N1 influenza viruses may be more important than previously estimated. This cross-immunity could provide a possible explanation of the relatively mild profile of the recent influenza pandemic. PMID:20543954

  3. Molecular character of influenza A/H1N1 2009: Implications for spread and control.

    PubMed

    Aras, Siddhesh; Aiyar, Ashok; Amedee, Angela M; Gallaher, William R

    2009-12-01

    The world is experiencing a pandemic of influenza that emerged in March 2009, due to a novel strain designated influenza A/H1N1 2009. This strain is closest in molecular sequence to swine influenza viruses, but differs from all previously known influenza by a minimum of 6.1%, and from prior "seasonal" H1N1 by 27.2%, giving it great potential for widespread human infection. While spread into India was delayed for two months by an aggressive interdiction program, since 1 August 2009 most cases in India have been indigenous. H1N1 2009 has differentially struck younger patients who are naïve susceptibles to its antigenic subtype, while sparing those >60 who have crossreactive antibody from prior experience with influenza decades ago and the 1977 "swine flu" vaccine distributed in the United States. It also appears to more severely affect pregnant women. It emanated from a single source in central Mexico, but its precise geographical and circumstantial origins, from either Eurasia or the Americas, remain uncertain. While currently a mild pandemic by the standard of past pandemics, the seriousness of H1N1 2009 especially among children should not be underestimated. There is potential for the virus, which continues to adapt to humans, to change over time into a more severe etiologic agent by any of several foreseeable mutations. Mass acceptance of the novel H1N1 2009 vaccine worldwide will be essential to its control. Having spread globally in a few months, affecting millions of people, it is likely to remain circulating in the human population for a decade or more.

  4. Academics and competing interests in H1N1 influenza media reporting

    PubMed Central

    Mandeville, Kate L; O'Neill, Sam; Brighouse, Andrew; Walker, Alice; Yarrow, Kielan; Chan, Kenneth

    2014-01-01

    Background 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. Methods 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. Results 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). Conclusions 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. PMID:24218071

  5. Nosocomial Pandemic (H1N1) 2009, United Kingdom, 2009–2010

    PubMed Central

    Myles, Puja R.; Openshaw, Peter J.M.; Gadd, Elaine M.; Lim, Wei Shen; Semple, Malcolm G.; Read, Robert C.; Taylor, Bruce L.; McMenamin, James; Armstrong, Colin; Bannister, Barbara; Nicholson, Karl G.; Nguyen-Van-Tam, Jonathan S.

    2011-01-01

    To determine clinical characteristics of patients hospitalized in the United Kingdom with pandemic (H1N1) 2009, we studied 1,520 patients in 75 National Health Service hospitals. We characterized patients who acquired influenza nosocomially during the pandemic (H1N1) 2009 outbreak. Of 30 patients, 12 (80%) of 15 adults and 14 (93%) of 15 children had serious underlying illnesses. Only 12 (57%) of 21 patients who received antiviral therapy did so within 48 hours after symptom onset, but 53% needed escalated care or mechanical ventilation; 8 (27%) of 30 died. Despite national guidelines and standardized infection control procedures, nosocomial transmission remains a problem when influenza is prevalent. Health care workers should be routinely offered influenza vaccine, and vaccination should be prioritized for all patients at high risk. Staff should remain alert to the possibility of influenza in patients with complex clinical problems and be ready to institute antiviral therapy while awaiting diagnosis during influenza outbreaks. PMID:21470446

  6. Monitoring and Characterization of Oseltamivir-Resistant Pandemic (H1N1) 2009 Virus, Japan, 2009–2010

    PubMed Central

    Ujike, Makoto; Ejima, Miho; Anraku, Akane; Shimabukuro, Kozue; Obuchi, Masatsugu; Kishida, Noriko; Hong, Xu; Takashita, Emi; Fujisaki, Seiichiro; Yamashita, Kazuyo; Horikawa, Hiroshi; Kato, Yumiko; Oguchi, Akio; Fujita, Nobuyuki; Tashiro, Masato

    2011-01-01

    To monitor and characterize oseltamivir-resistant (OR) pandemic (H1N1) 2009 virus with the H275Y mutation, we analyzed 4,307 clinical specimens from Japan by neuraminidase (NA) sequencing or inhibition assay; 61 OR pandemic (H1N1) 2009 viruses were detected. NA inhibition assay and M2 sequencing indicated that OR pandemic (H1N1) 2009 virus was resistant to M2 inhibitors, but sensitive to zanamivir. Full-genome sequencing showed OR and oseltamivir-sensitive (OS) viruses had high sequence similarity, indicating that domestic OR virus was derived from OS pandemic (H1N1) 2009 virus. Hemagglutination inhibition test demonstrated that OR and OS pandemic (H1N1) 2009 viruses were antigenically similar to the A/California/7/2009 vaccine strain. Of 61 case-patients with OR viruses, 45 received oseltamivir as treatment, and 10 received it as prophylaxis, which suggests that most cases emerged sporadically from OS pandemic (H1N1) 2009, due to selective pressure. No evidence of sustained spread of OR pandemic (H1N1) 2009 was found in Japan; however, 2 suspected incidents of human-to-human transmission were reported. PMID:21392439

  7. Trust during the early stages of the 2009 H1N1 pandemic.

    PubMed

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

    2014-01-01

    Distrust of the government often stands in the way of cooperation with public health recommendations in a crisis. The purpose of this article is to describe the public's trust in government recommendations during the early stages of the H1N1 pandemic and to identify factors that might account for these trust levels. The authors surveyed 1,543 respondents about their experiences and attitudes related to H1N1 influenza between June 3, 2009, and July 6, 2009, during the first wave of the pandemic using the Knowledge Networks online panel. This panel is representative of the U.S. population and uses a combination of random digit dialing and address-based probability sampling frames covering 99% of the U.S. household population to recruit participants. To ensure participation of low-income individuals and those without Internet access, Knowledge Networks provides hardware and access to the Internet if needed. Measures included standard demographics, a trust scale, trust ratings for individual spokespersons, involvement with H1N1, experience with H1N1, and past discrimination in health care. The authors found that trust of government was low (2.3 out of 4) and varied across demographic groups. Blacks and Hispanics reported higher trust in government than did Whites. Of the spokespersons included, personal health professionals received the highest trust ratings and religious leaders the lowest. Attitudinal and experience variables predicted trust better than demographic characteristics. Closely following the news about the flu virus, having some self-reported knowledge about H1N1, self-reporting of local cases, and previously experiencing discrimination were the significant attitudinal and experience predictors of trust. Using a second longitudinal survey, trust in the early stages of the pandemic predicted vaccine acceptance later but only for White, non-Hispanic individuals.

  8. Predominance of heterosubtypic IFN-γ-only-secreting effector memory T cells in pandemic H1N1 naive adults

    PubMed Central

    Sridhar, Saranya; Begom, Shaima; Bermingham, Alison; Ziegler, Thedi; Roberts, Kim L.; Barclay, Wendy S.; Openshaw, Peter; Lalvani, Ajit

    2015-01-01

    The 2009/10 pandemic (pH1N1) highlighted the need for vaccines conferring heterosubtypic immunity against antigenically shifted influenza strains. Although cross-reactive T cells are strong candidates for mediating heterosubtypic immunity, little is known about the population-level prevalence, frequency, and cytokine-secretion profile of heterosubtypic T cells to pH1N1. To assess this, pH1N1 sero-negative adults were recruited. Single-cell IFN-γ and IL-2 cytokine-secretion profiles to internal proteins of pH1N1 or live virus were enumerated and characterised. Heterosubtypic T cells recognising pH1N1 core proteins were widely prevalent, being detected in 90% (30 of 33) of pH1N1-näive individuals. Although the last exposure to influenza was greater than 6 months ago, the frequency and proportion of the IFN-γ-only-secreting T-cell subset was significantly higher than the IL-2-only-secreting subset. CD8+ IFN-γ-only-secreting heterosubtypic T cells were predominantly CCR7−CD45RA− effector-memory phenotype, expressing the tissue-homing receptor CXCR3 and degranulation marker CD107. Receipt of the 2008–09 influenza vaccine did not alter the frequency of these heterosubtypic T cells, highlighting the inability of current vaccines to maintain this heterosubtypic T-cell pool. The surprisingly high prevalence of pre-existing circulating pH1N1-specific CD8+ IFN-γ-only-secreting effector memory T cells with cytotoxic and lung-homing potential in pH1N1-seronegative adults may partly explain the low case fatality rate despite high rates of infection of the pandemic in young adults. PMID:22777887

  9. Neurological events related to influenza A (H1N1) pdm09

    PubMed Central

    Cárdenas, Graciela; Soto-Hernández, José Luis; Díaz-Alba, Alexandra; Ugalde, Yair; Mérida-Puga, Jorge; Rosetti, Marcos; Sciutto, Edda

    2014-01-01

    Objectives To review neurological complications after the influenza A (H1N1) pdm09, highlighting the clinical differences between patients with post-vaccine or viral infection. Design A search on Medline, Ovid, EMBASE, and PubMed databases using the keywords “neurological complications of Influenza AH1N1” or “post-vaccine Influenza AH1N1.” Setting Only papers written in English, Spanish, German, French, Portuguese, and Italian published from March 2009 to December 2012 were included. Sample We included 104 articles presenting a total of 1636 patient cases. In addition, two cases of influenza vaccine-related neurological events from our neurological care center, arising during the period of study, were also included. Main outcome measures Demographic data and clinical diagnosis of neurological complications and outcomes: death, neurological sequelae or recovery after influenza A (H1N1) pdm09 vaccine or infection. Results The retrieved cases were divided into two groups: the post-vaccination group, with 287 patients, and the viral infection group, with 1349 patients. Most patients in the first group were adults. The main neurological complications were Guillain-Barre syndrome (GBS) or polyneuropathy (125), and seizures (23). All patients survived. Pediatric patients were predominant in the viral infection group. In this group, 60 patients (4.7%) died and 52 (30.1%) developed permanent sequelae. A wide spectrum of neurological complications was observed. Conclusions Fatal cases and severe, permanent, neurological sequelae were observed in the infection group only. Clinical outcome was more favorable in the post-vaccination group. In this context, the relevance of an accurate neurological evaluation is demonstrated for all suspicious cases, as well as the need of an appropriate long-term clinical and imaging follow-up of infection and post-vaccination events related to influenza A (H1N1) pdm09, to clearly estimate the magnitude of neurological complications

  10. Evaluation of safety and immunogenicity of HNVAC, an MDCK-based H1N1 pandemic influenza vaccine, in Phase I single centre and Phase II/III multi-centre, double-blind, randomized, placebo-controlled, parallel assignment studies.

    PubMed

    Basavaraj, V H; Sampath, G; Hegde, Nagendra R; Mohan, V Krishna; Ella, Krishna M

    2014-07-31

    The clinical evaluation of the MDCK-based H1N1 pandemic influenza vaccine HNVAC in adults aged 18-65 years is reported. In the Phase I randomized, double-blind, placebo-controlled, single-centre study, 160 subjects were parallelly assigned 3:1 to vaccine:placebo groups (n=60:20) with both the aluminium hydroxide adjuvanted and non-adjuvanted vaccine formulations. A single dose of both the formulations containing 15 μg of haemagglutinin protein showed minimal adverse reactions, the most common of which were pain at injection site (11.67%) and fever (10.00%). Both formulations produced 74-81% seroprotection (SRP: titre of ≥40), 67-70% seroconversion (SRC: four-fold increase in titres between days 0 and 21), and a four-fold increase in geometric mean titres (GMT). Aluminium hydroxide did not have a significant effect either on immunogenicity or on reactogenicity. Nevertheless, based on its recognized positive effects on the stability and immunogenicity of many vaccines, and its marginal benefit in both pre-clinical and Phase I studies of HNVAC, alum adjuvanted HNVAC was further tested in a staggered Phase II/III randomized, double-blind, placebo-controlled, multi-centre study of 200 and 195 subjects, respectively, parallelly assigned 4:1 to adjuvanted vaccine and placebo groups. In these studies, the most common adverse reactions were pain at injection site (6.88% and 5.77% in Stage 1 and Stage 2, respectively) and fever (7.50% and 7.05%, respectively), and a single dose resulted in 87-90% SRP, 85-86% SRC, and a nearly six-fold increase in GMT, meeting or exceeding licensing criteria. It is concluded that HNVAC is safe and immunogenic to adults of 18-65 years.

  11. Protecting the Public from H1N1 through Points of Dispensing (PODs).

    PubMed

    Rinchiuso-Hasselmann, Anne; McKay, Ryan L; Williams, Christopher A; Starr, David T; Morgenthau, Beth Maldin; Zucker, Jane R; Raphael, Marisa

    2011-03-01

    In fall 2009, the New York City Department of Health and Mental Hygiene (DOHMH) operated 58 points of dispensing (PODs) over 5 weekends to provide influenza A (H1N1) 2009 monovalent vaccination to New Yorkers. Up to 7 sites were opened each day across the 5 boroughs, with almost 50,000 New Yorkers being vaccinated. The policies and protocols used were based on those developed for New York City's POD Plan, the cornerstone of the city's mass prophylaxis planning. Before the H1N1 experience, NYC had not opened more than 5 PODs simultaneously and had only experienced the higher patient volume seen with the H1N1 PODs on 1 prior occasion. Therefore, DOHMH identified factors that contributed to the success of POD operations, as well as areas for improvement to inform future mass prophylaxis planning and response. Though this was a relatively small-scale, preplanned operation, during which a maximum of 7 PODs were operated on a given day, the findings have implications for larger-scale mass prophylaxis planning for emergencies.

  12. [Mass communication during the "H1N1 flu"].

    PubMed

    Pellegrino, E; Martino, G; Balli, M; Puggelli, F; Tiscione, E; Bonaccorsi, G; Bonanni, P

    2012-01-01

    Nowadays communication plays a key role in healthcare, especially when a detailed risk analysis is important for correct information, as in the case of the H1N1 flu virus A. Through our study we have analyzed how the event "H1N1 flu" was addressed by the media, considering the period April 2009-June 2010. We collected the information from "Il Corriere della Sera", "La Repubblica" and "City", in addition to an online site for general information such as "TGCOM". The analyzed peak of daily news was seen a few weeks before the pandemic peak; in addition, after the peak of the pandemic, the interest of the press has completely collapsed, and eventually disappeared altogether. The media can influence the thought and consequentially how the recipients act, leading to a misperception of risk ('risk') and danger ('hazard'). Moreover the institutions and health professionals are not always able to communicate effectively to meet the needs for correct information. It is desirable in the future a greater degree of collaboration between media and authorities to have a clearer simpler and less misleading communication in the health field, helping recipients to act properly.

  13. 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.

  14. Human swine influenza A [H1N1]: practical advice for clinicians early in the pandemic.

    PubMed

    Fitzgerald, Dominic A

    2009-09-01

    The influenza pandemic the world was waiting for may have arrived, but the early indications are that the first wave of human swine influenza A [H1N1], also referred to as H1N1 Mexico 09 or "swine flu", is highly transmissible but of no greater virulence than seasonal influenza to date. The new swine flu H1N1 virus is a mixture of avian, porcine and human influenza RNA. With twenty thousand confirmed cases worldwide and 117 deaths within 7 weeks of the first acknowledgement of a possible pandemic by Mexican and WHO experts, the mortality rate is less than 0.1% and the majority of deaths centred upon the origin of the epidemic in Mexico [83%]. Swine flu is thus far a relatively mild illness seen predominantly in those who are healthy and under 25 years of age, perhaps reflecting protection from previous human influenza exposure in older people. As the virus spreads internationally, border protection issues have surfaced and public health initiatives are being progressively rolled out to minimise the transmission. Vaccines are being developed which will be trialled in the coming months with a likely availability by August 2009, in time for the northern hemisphere autumn and winter. Vigilance without alarm appears to be the recommendation so far.

  15. Induction of cell surface human leukocyte antigen-G expression in pandemic H1N1 2009 and seasonal H1N1 influenza virus-infected patients.

    PubMed

    Chen, Hai-Xiao; Chen, Bao-Guo; Shi, Wei-Wu; Zhen, Rui; Xu, Dan-Ping; Lin, Aifen; Yan, Wei-Hua

    2011-02-01

    A novel H1N1 virus of swine origin (H1N1v) recently caused a pandemic; however, knowledge of immunologic aspects of the virus infection are limited. Human leukocyte antigen-G (HLA-G) was speculated to play critical roles in viral infection, although its clinical relevance in H1N1 infection remains unknown. In this study, HLA-G expression in peripheral T lymphocytes, monocytes, and CD4(+) CD25(+) FoxP3+ regulatory T (Treg) cells (in 50 H1N1v-infected and 41 seasonal H1N1-infected patients and 27 control subjects) were analyzed by flow cytometry. Plasma-soluble HLA-G (sHLA-G, in 28 H1N1v-infected, 29 seasonal H1N1-infected patients and 85 control subjects) were determined with enzyme-linked immunosorbent assay. The percentage of HLA-G-positive T lymphocytes and monocytes among patients with H1N1v and seasonal H1N1 infections was dramatically increased compared with controls (all p < 0.001). Treg was markedly increased among H1N1v- infected patients compared with normal controls (p = 0.041), but not for the seasonal H1N1-infected patients. Meanwhile, no significant difference was observed for sHLA-G levels between the groups. Together, cell surface HLA-G expression was markedly induced in H1N1v-infected and seasonal H1N1-infected patients, and increased Treg was observed only in H1N1v-infected patients. Given its immune-suppressive property, elevated cell surface HLA-G expression may help to explain the virus escaping from host immune responses.

  16. Influenza A H1N1 2009 (Swine Flu) and Pregnancy.

    PubMed

    Lim, Boon H; Mahmood, Tahir A

    2011-08-01

    The Influenza A H1N1 pandemic (A H1N1) occurred between June 2009 and August 2010. Although the pandemic is now over, the virus has emerged as the predominant strain in the current seasonal influenza phase in the northern hemisphere. The A H1N1 influenza is a novel strain of the influenza A virus and is widely known as swine flu. The virus contains a mixture of genetic material from human, pig and bird flu virus. It is a new variety of flu which people have not had much immunity to. Much has been learnt from the Pandemic of 2009/2010 but the messages about vaccination and treatment seem to be taken slowly by the clinical profession. Most people affected by the virus, including pregnant women, suffer a mild viral illness, and make a full recovery. The median duration of illness is around seven days. This influenza typically affects the younger age group i.e. from the ages of 5-65 years. Current experience shows that the age group experiencing increased morbidity and mortality rates are in those under 65 years of age. Pregnant women, because of their altered immunity and physiological adaptations, are at higher risk of developing pulmonary complications, especially in the second and third trimesters. In the United Kingdom, twelve maternal deaths were reported to be associated with the H1N1 virus during the pandemic and clear avoidable factors were identified (Modder, Review of Maternal Deaths in the UK related to A H1N1 2009 influenza (CMACE). www.cmace.org.uk, 2010). The pregnancy outcomes were also poor for women who were affected by the virus with a fivefold increase in the perinatal mortality rate and threefold increase in the preterm delivery rate (Yates et al. Health Technol Assess 14(34):109-182, 2010). There continues to be a low uptake of the flu vaccine and commencement of antiviral treatment for pregnant women.

  17. Cytotoxic T lymphocytes established by seasonal human influenza cross-react against 2009 pandemic H1N1 influenza virus.

    PubMed

    Tu, Wenwei; Mao, Huawei; Zheng, Jian; Liu, Yinping; Chiu, Susan S; Qin, Gang; Chan, Ping-Lung; Lam, Kwok-Tai; Guan, Jing; Zhang, Lijuan; Guan, Yi; Yuen, Kwok-Yung; Peiris, J S Malik; Lau, Yu-Lung

    2010-07-01

    While few children and young adults have cross-protective antibodies to the pandemic H1N1 2009 (pdmH1N1) virus, the illness remains mild. The biological reasons for these epidemiological observations are unclear. In this study, we demonstrate that the bulk memory cytotoxic T lymphocytes (CTLs) established by seasonal influenza viruses from healthy individuals who have not been exposed to pdmH1N1 can directly lyse pdmH1N1-infected target cells and produce gamma interferon (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha). Using influenza A virus matrix protein 1 (M1(58-66)) epitope-specific CTLs isolated from healthy HLA-A2(+) individuals, we further found that M1(58-66) epitope-specific CTLs efficiently killed both M1(58-66) peptide-pulsed and pdmH1N1-infected target cells ex vivo. These M1(58-66)-specific CTLs showed an effector memory phenotype and expressed CXCR3 and CCR5 chemokine receptors. Of 94 influenza A virus CD8 T-cell epitopes obtained from the Immune Epitope Database (IEDB), 17 epitopes are conserved in pdmH1N1, and more than half of these conserved epitopes are derived from M1 protein. In addition, 65% (11/17) of these epitopes were 100% conserved in seasonal influenza vaccine H1N1 strains during the last 20 years. Importantly, seasonal influenza vaccination could expand the functional M1(58-66) epitope-specific CTLs in 20% (4/20) of HLA-A2(+) individuals. Our results indicated that memory CTLs established by seasonal influenza A viruses or vaccines had cross-reactivity against pdmH1N1. These might explain, at least in part, the unexpected mild pdmH1N1 illness in the community and also might provide some valuable insights for the future design of broadly protective vaccines to prevent influenza, especially pandemic influenza.

  18. Bayesian coalescent analysis of pandemic H1N1 influenza A virus circulating in the South American region.

    PubMed

    Goñi, Natalia; Moratorio, Gonzalo; Coppola, Leticia; Ramas, Viviana; Comas, Victoria; Soñora, Martin; Chiparelli, Hector; Cristina, Juan

    2012-12-01

    The first influenza pandemic of this century was declared in April of 2009, with the emergence of a novel H1N1 influenza A virus strain (H1N1pdm). Understanding the evolution of H1N1pdm populations within the South American region is essential for studying global diversification, emergence, resistance and vaccine efficacy. In order to gain insight into these matters, we have performed a Bayesian coalescent Markov Chain Monte Carlo analysis of hemagglutinin (HA) and neuraminidase (NA) gene sequences of all available and comparable HA and NA sequences obtained from H1N1pdm IAV circulating in the South American region. High evolutionary rates and fast population growths characterize the population dynamics of H1N1pdm strains in this region of the world. A significant contribution of first codon position to the mean evolutionary rate was found for both genes studied, revealing a high contribution of non-synonymous substitutions to the mean substitution rate. In the 178days period covered by these studies, substitutions in all HA epitope regions can be observed. HA substitutions D239G/N and Q310H have been observed only in Brazilian patients. While substitution D239G/N is not particularly associated to a specific genetic lineage, all strains bearing substitution Q310H were assigned to clade 6, suggesting a founder effect. None of the substitutions found in the NA proteins of H1N1pdm strains isolated in South America appears sufficiently close to affect the drug binding pocket for the three NA inhibitor antivirals tested. A more detailed analysis of NA proteins revealed epitope differences among 2010 vaccine and H1N1pdm IAV strains circulating in the South American region.

  19. Modeling influenza epidemics and pandemics: insights into the future of swine flu (H1N1).

    PubMed

    Coburn, Brian J; Wagner, Bradley G; Blower, Sally

    2009-06-22

    Here we present a review of the literature of influenza modeling studies, and discuss how these models can provide insights into the future of the currently circulating novel strain of influenza A (H1N1), formerly known as swine flu. We discuss how the feasibility of controlling an epidemic critically depends on the value of the Basic Reproduction Number (R0). The R0 for novel influenza A (H1N1) has recently been estimated to be between 1.4 and 1.6. This value is below values of R0 estimated for the 1918-1919 pandemic strain (mean R0 approximately 2: range 1.4 to 2.8) and is comparable to R0 values estimated for seasonal strains of influenza (mean R0 1.3: range 0.9 to 2.1). By reviewing results from previous modeling studies we conclude it is theoretically possible that a pandemic of H1N1 could be contained. However it may not be feasible, even in resource-rich countries, to achieve the necessary levels of vaccination and treatment for control. As a recent modeling study has shown, a global cooperative strategy will be essential in order to control a pandemic. This strategy will require resource-rich countries to share their vaccines and antivirals with resource-constrained and resource-poor countries. We conclude our review by discussing the necessity of developing new biologically complex models. We suggest that these models should simultaneously track the transmission dynamics of multiple strains of influenza in bird, pig and human populations. Such models could be critical for identifying effective new interventions, and informing pandemic preparedness planning. Finally, we show that by modeling cross-species transmission it may be possible to predict the emergence of pandemic strains of influenza.

  20. Antibody recognition of the pandemic H1N1 Influenza virus hemagglutinin receptor binding site.

    PubMed

    Hong, Minsun; Lee, Peter S; Hoffman, Ryan M B; Zhu, Xueyong; Krause, Jens C; Laursen, Nick S; Yoon, Sung-Il; Song, Langzhou; Tussey, Lynda; Crowe, James E; Ward, Andrew B; Wilson, Ian A

    2013-11-01

    Influenza virus is a global health concern due to its unpredictable pandemic potential. This potential threat was realized in 2009 when an H1N1 virus emerged that resembled the 1918 virus in antigenicity but fortunately was not nearly as deadly. 5J8 is a human antibody that potently neutralizes a broad spectrum of H1N1 viruses, including the 1918 and 2009 pandemic viruses. Here, we present the crystal structure of 5J8 Fab in complex with a bacterially expressed and refolded globular head domain from the hemagglutinin (HA) of the A/California/07/2009 (H1N1) pandemic virus. 5J8 recognizes a conserved epitope in and around the receptor binding site (RBS), and its HCDR3 closely mimics interactions of the sialic acid receptor. Electron microscopy (EM) reconstructions of 5J8 Fab in complex with an HA trimer from a 1986 H1 strain and with an engineered stabilized HA trimer from the 2009 H1 pandemic virus showed a similar mode of binding. As for other characterized RBS-targeted antibodies, 5J8 uses avidity to extend its breadth and affinity against divergent H1 strains. 5J8 selectively interacts with HA insertion residue 133a, which is conserved in pandemic H1 strains and has precluded binding of other RBS-targeted antibodies. Thus, the RBS of divergent HAs is targeted by 5J8 and adds to the growing arsenal of common recognition motifs for design of therapeutics and vaccines. Moreover, consistent with previous studies, the bacterially expressed H1 HA properly refolds, retaining its antigenic structure, and presents a low-cost and rapid alternative for engineering and manufacturing candidate flu vaccines.

  1. Extreme evolutionary conservation of functionally important regions in H1N1 influenza proteome.

    PubMed

    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

  2. rapidSTRIPE H1N1 test for detection of the pandemic swine origin influenza A (H1N1) virus.

    PubMed

    Patel, Pranav; Graser, Elmara; Robst, Stephan; Hillert, Roger; Meye, Axel; Hillebrand, Timo; Niedrig, Matthias

    2011-04-01

    The rapidSTRIPE H1N1 test, based on a nucleic acid lateral-flow assay, has been developed for diagnosis of a swine-origin influenza A (H1N1) virus. This test is simple and cost-effective and allows specific detection of the S-OIV A (H1N1) virus from swab sampling to final detection on a lateral-flow stripe within 2 to 3 h.

  3. Cross-reactive CD8+ T-cell immunity between the pandemic H1N1-2009 and H1N1-1918 influenza A viruses.

    PubMed

    Gras, Stephanie; Kedzierski, Lukasz; Valkenburg, Sophie A; Laurie, Karen; Liu, Yu Chih; Denholm, Justin T; Richards, Michael J; Rimmelzwaan, Guus F; Kelso, Anne; Doherty, Peter C; Turner, Stephen J; Rossjohn, Jamie; Kedzierska, Katherine

    2010-07-13

    Preexisting T-cell immunity directed at conserved viral regions promotes enhanced recovery from influenza virus infections, with there being some evidence of cross-protection directed at variable peptides. Strikingly, many of the immunogenic peptides derived from the current pandemic A(H1N1)-2009 influenza virus are representative of the catastrophic 1918 "Spanish flu" rather than more recent "seasonal" strains. We present immunological and structural analyses of cross-reactive CD8(+) T-cell-mediated immunity directed at a variable (although highly cross-reactive) immunodominant NP(418-426) peptide that binds to a large B7 family (HLA-B*3501/03/0702) found throughout human populations. Memory CD8(+) T-cell specificity was probed for 12 different NP(418) mutants that emerged over the 9 decades between the 1918 and 2009 pandemics. Although there is evidence of substantial cross-reactivity among seasonal NP(418) mutants, current memory T-cell profiles show no preexisting immunity to the 2009-NP(418) variant or the 1918-NP(418) variant. Natural infection with the A(H1N1)-2009 virus, however, elicits CD8(+) T cells specific for the 2009-NP(418) and 1918-NP(418) epitopes. This analysis points to the potential importance of cross-reactive T-cell populations that cover the possible spectrum of T-cell variants and suggests that the identification of key residues/motifs that elicit cross-reactive T-cell sets could facilitate the evolution of immunization protocols that provide a measure of protection against unpredicted pandemic influenza viruses. Thus, it is worth exploring the potential of vaccines that incorporate peptide variants with a proven potential for broader immunogenicity, especially to those that are not recognized by the current memory T-cell pool generated by exposure to influenza variants that cause successive seasonal epidemics.

  4. Agglutination of human O erythrocytes by influenza A(H1N1) viruses freshly isolated from patients.

    PubMed

    Murakami, T; Haruki, K; Seto, Y; Kimura, T; Minoshiro, S; Shibe, K

    1991-04-01

    The hemagglutinin titers of 10 influenza A (H1N1) viruses were examined using the erythrocytes of several species. Human O erythrocytes showed the highest agglutination titer to the viruses, whereas chicken erythrocytes showed a low titer. These findings were noted for at least 10 passages by serial dilutions of the viruses in Madin-Darby canine kidney (MDCK) cells. All influenza A(H1N1) viruses, plaque-cloned directly from throat-washing specimens of patients, also agglutinated human O but not chicken erythrocytes. The results of a hemadsorption test indicated that chicken erythrocytes possess less affinity to MDCK cells infected with the A/Osaka City/2/88(H1N1) stain than to those infected with the A/Yamagata/120/86(H1N1) strain which is used as an inactivated influenza vaccine in Japan. However, there were no significant differences between the A/Osaka City/2/88 and the A/Yamagata/120/86 strains in the hemagglutination inhibition test. Since human O erythrocytes have high agglutination activity to influenza A(H1N1) and also to A(H3N2) and B viruses in MDCK cells, these erythrocytes may be useful for the serological diagnosis of influenza.

  5. Pandemic influenza A(H1N1) 2009 virus in pregnancy.

    PubMed

    Liu, She-Lan; Wang, Jing; Yang, Xu-Hui; Chen, Jin; Huang, Ren-Jie; Ruan, Bing; He, Hong-Xuan; Wang, Cheng-Min; Zhang, Hong-Mei; Sun, Zhou; Xie, Li; Zhuang, Hui

    2013-01-01

    Two hundred fourteen abstracts and 87 full texts regarding pregnant women infected with pandemic influenza A(H1N1) 2009 virus were systematically reviewed by using a PubMed search and assessing pandemic, clinical, laboratory test, vaccine, and control experiences. Both policy and health education were excluded. This review counted the total number of pregnant cases from different countries and analyzed their epidemic features, including trimester distribution, morbidity, hospitalization, intensive care unit admissions, maternal mortality, underlying diseases, complications, high-risk factors for death, pregnancy outcome, and clinical symptoms compared with the previous pandemic seasonal influenza A/H1N1 as compared with the general population. Early identification and treatment were the most important factors in different countries and areas examined. The vaccine and antiviral drugs that have been the most efficient means to control the novel virus appear to be safe but require more extensive study. In the future, the focus should be placed on understanding vertical transmission and the severe mechanisms.

  6. Modelling during an emergency: the 2009 H1N1 influenza pandemic.

    PubMed

    Lee, B Y; Haidari, L A; Lee, M S

    2013-11-01

    During the 2009 H1N1 pandemic, decision-makers had access to mathematical and computational models that were not available in previous pandemics in 1918, 1957, and 1968. How did models contribute to policy and action during the 2009 H1N1 pandemic? Modelling encountered six primary challenges: (i) expectations of modelling were not clearly defined; (ii) appropriate real-time data were not readily available; (iii) modelling results were not generated, shared, or disseminated in time; (iv) decision-makers could not always decipher the structure and assumptions of the models; (v) modelling studies varied in intervention representations and reported results; and (vi) modelling studies did not always present the results or outcomes that are useful to decision-makers. However, there were also seven general successes: (i) modelling characterized the role of social distancing measures such as school closure; (ii) modelling helped to guide data collection; (iii) modelling helped to justify the value of the vaccination programme; (iv) modelling helped to prioritize target populations for vaccination; (v) modelling addressed the use of antiviral medications; (vi) modelling helped with health system preparedness planning; and (vii) modellers and decision-makers gained a better understanding of how to work with each other. In many ways, the 2009 pandemic served as practice and a learning opportunity for both modellers and decision-makers. Modellers can continue working with decision-makers and other stakeholders to help overcome these challenges, to be better prepared when the next emergency inevitably arrives.

  7. Modelling the transmission dynamics and control of the novel 2009 swine influenza (H1N1) pandemic.

    PubMed

    Sharomi, O; Podder, C N; Gumel, A B; Mahmud, S M; Rubinstein, E

    2011-03-01

    The paper presents a deterministic compartmental model for the transmission dynamics of swine influenza (H1N1) pandemic in a population in the presence of an imperfect vaccine and use of drug therapy for confirmed cases. Rigorous analysis of the model, which stratifies the infected population in terms of their risk of developing severe illness, reveals that it exhibits a vaccine-induced backward bifurcation when the associated reproduction number is less than unity. The epidemiological consequence of this result is that the effective control of H1N1, when the reproduction number is less than unity, in the population would then be dependent on the initial sizes of the subpopulations of the model. For the case where the vaccine is perfect, it is shown that having the reproduction number less than unity is necessary and sufficient for effective control of H1N1 in the population (in such a case, the associated disease-free equilibrium is globally asymptotically stable). The model has a unique endemic equilibrium when the reproduction number exceeds unity. Numerical simulations of the model, using data relevant to the province of Manitoba, Canada, show that it reasonably mimics the observed H1N1 pandemic data for Manitoba during the first (Spring) wave of the pandemic. Further, it is shown that the timely implementation of a mass vaccination program together with the size of the Manitoban population that have preexisting infection-acquired immunity (from the first wave) are crucial to the magnitude of the expected burden of disease associated with the second wave of the H1N1 pandemic. With an estimated vaccine efficacy of approximately 80%, it is projected that at least 60% of Manitobans need to be vaccinated in order for the effective control or elimination of the H1N1 pandemic in the province to be feasible. Finally, it is shown that the burden of the second wave of H1N1 is expected to be at least three times that of the first wave, and that the second wave would last

  8. Factors Influencing School Closure and Dismissal Decisions: Influenza A (H1N1), Michigan 2009

    ERIC Educational Resources Information Center

    Dooyema, Carrie A.; Copeland, Daphne; Sinclair, Julie R.; Shi, Jianrong; Wilkins, Melinda; Wells, Eden; Collins, Jim

    2014-01-01

    Background: In fall 2009, many US communities experienced school closures during the influenza A H1N1 pandemic (pH1N1) and the state of Michigan reported 567 closures. We conducted an investigation in Michigan to describe pH1N1-related school policies, practices, and identify factors related to school closures. Methods: We distributed an online…

  9. Characterization of H1N1 swine influenza viruses circulating in Canadian pigs in 2009

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The 2009 pandemic H1N1 (pH1N1), of apparent swine origin, may have evolved in pigs unnoticed because of insufficient surveillance. Consequently, the need for surveillance of influenza viruses circulating in pigs has received added attention. In this study we characterized H1N1 viruses isolated from ...

  10. Antibody-Dependent Cell-Mediated Cytotoxicity Epitopes on the Hemagglutinin Head Region of Pandemic H1N1 Influenza Virus Play Detrimental Roles in H1N1-Infected Mice

    PubMed Central

    Ye, Zi-Wei; Yuan, Shuofeng; Poon, Kwok-Man; Wen, Lei; Yang, Dong; Sun, Zehua; Li, Cun; Hu, Meng; Shuai, Huiping; Zhou, Jie; Zhang, Mei-Yun; Zheng, Bo-Jian; Chu, Hin; Yuen, Kwok-Yung

    2017-01-01

    Engaging the antibody-dependent cell-mediated cytotoxicity (ADCC) for killing of virus-infected cells and secretion of antiviral cytokines and chemokines was incorporated as one of the important features in the design of universal influenza vaccines. However, investigation of the ADCC epitopes on the highly immunogenic influenza hemagglutinin (HA) head region has been rarely reported. In this study, we determined the ADCC and antiviral activities of two putative ADCC epitopes, designated E1 and E2, on the HA head of a pandemic H1N1 influenza virus in vitro and in a lethal mouse model. Our data demonstrated that sera from the E1-vaccinated mice could induce high ADCC activities. Importantly, the induction of ADCC response modestly decreased viral load in the lungs of H1N1-infected mice. However, the elevated ADCC significantly increased mouse alveolar damage and mortality than that of the PBS-vaccinated group (P < 0.0001). The phenotype was potentially due to an exaggerated inflammatory cell infiltration triggered by ADCC, as an upregulated release of cytotoxic granules (perforin) was observed in the lung tissue of E1-vaccinated mice after H1N1 influenza virus challenge. Overall, our data suggested that ADCC elicited by certain domains of HA head region might have a detrimental rather than protective effect during influenza virus infection. Thus, future design of universal influenza vaccine shall strike a balance between the induction of protective immunity and potential side effects of ADCC. PMID:28377769

  11. 2009 H1N1 influenza: a twenty-first century pandemic with roots in the early twentieth century.

    PubMed

    Farley, Monica M

    2010-09-01

    A swine-origin H1N1 triple-reassortant influenza A virus found to be a distant relative of the 1918 "Spanish flu" virus emerged in April 2009 to give rise to the first influenza pandemic of the 21st century. Although disease was generally mild and similar to seasonal influenza, severe manifestations including respiratory failure were noted in some, particularly those with underlying conditions such as asthma, pregnancy and immunosuppression. Children and younger adults accounted for most cases, hospitalizations and deaths. A reverse transcriptase-polymerase chain reaction assay was superior to antigen-based rapid tests for diagnosis. All 2009 H1N1 pandemic influenza strains were susceptible to 1 or more neuraminidase inhibitors. Monovalent, unadjuvanted 2009 H1N1 vaccines were licensed in the United States in September 2009 and initially targeted to younger individuals, pregnant women, caretakers of infants and healthcare providers. The 2009 H1N1 pandemic highlights the need for modernization of influenza vaccines, improved diagnostics and more rigorous evaluation of mitigation strategies.

  12. Perspectives from Spanish infectious diseases professionals on 2009 A (H1N1) influenza: the third half.

    PubMed

    Paño-Pardo, J R; Martín-Quirós, A; Romero-Gómez, M; Maldonado, J; Martín-Vega, A; Rico-Nieto, A; Mora-Rillo, M; Grill, F; García-Rodríguez, J; Arribas, J R; Carratalá, J; Rodríguez-Baño, J

    2011-06-01

    The first influenza pandemic in more than 40 years was declared in 2009. We aimed to evaluate the beliefs of Spanish infectious diseases professionals regarding several aspects of 2009 A (H1N1) influenza once the epidemic waned. An online survey was designed and distributed among members of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC). The survey considered hospital organization and preparedness planning and conduct, as well as the opinion of the infectious diseases professionals regarding several key issues. Between 7 March and 22 March 2010, 303 responses, corresponding to 12.8% of the SEIMC membership, were received. Of the respondents, 48.2% were microbiologists and 42.3% were clinicians dealing with infectious diseases. Forty-one per cent of respondents did not believe that 2009 A (H1N1) influenza had a more severe presentation than other seasonal influenzas. Only 5% fully agreed that 2009 A (H1N1) influenza had a more severe presentation. Influenza planning was available in 69.7% of represented institutions before the arrival of 2009 A (H1N1) influenza, and was considered to be useful, to different extents, by most professionals. In most institutions (88.3%), a multidisciplinary team was created to coordinate local pandemic influenza actions. The most successful protocols were those provided by regional healthcare authorities, followed by those from the CDC. The most problematic issues regarding 2009 A (H1N1) influenza were the management of patients in the emergency room and the vaccination and awareness of healthcare professionals (HCPs) regarding infection control. Microbiological diagnosis and the availability of antivirals were the least problematic areas. Although the majority of surveyed infectious diseases professionals did not believe that 2009 A (H1N1) influenza had an especially severe presentation, most of them agreed with the way that this epidemic was managed in their institutions.

  13. Genetic Characteristics and Immunogenicity of Pandemic H1N1 Influenza Virus Isolate from Pig in Korea

    PubMed Central

    Moon, Hyoung Joon; Oh, Jin Sik; Na, Woonsung; Yeom, Minjoo; Han, Sang Yoon; Kim, Sung Jae; Park, Bong Kyun

    2016-01-01

    A pandemic influenza A (H1N1) virus strain was isolated from a pig farm in Korea in December 2009. The strain was propagated in and isolated from both the Madin-Darby canine kidney cell line and embryonated eggs. The partial and complete sequences of the strain were identical to those of A/California/04/2009, with >99% sequence similarity in the HA, NA, M, NS, NP, PA, PB1, and PB2 genes. The isolated strain was inactivated and used to prepare a swine influenza vaccine. This trial vaccine, containing the new isolate that has high sequence similarity with the pandemic influenza A (H1N1) virus, resulted in seroconversion in Guinea pigs and piglets. This strain could therefore be a potential vaccine candidate for swine influenza control in commercial farms. PMID:27799877

  14. Pathogenesis and transmission of triple-reassortant swine H1N1 influenza viruses isolated before the 2009 H1N1 pandemic.

    PubMed

    Belser, Jessica A; Gustin, Kortney M; Maines, Taronna R; Blau, Dianna M; Zaki, Sherif R; Katz, Jacqueline M; Tumpey, Terrence M

    2011-02-01

    The 2009 H1N1 pandemic influenza virus represents the greatest incidence of human infection with an influenza virus of swine origin to date. Moreover, triple-reassortant swine (TRS) H1N1 viruses, which share similar host and lineage origins with 2009 H1N1 viruses, have been responsible for sporadic human cases since 2005. Similar to 2009 H1N1 viruses, TRS viruses are capable of causing severe disease in previously healthy individuals and frequently manifest with gastrointestinal symptoms; however, their ability to cause severe disease has not been extensively studied. Here, we evaluated the pathogenicity and transmissibility of two TRS viruses associated with disease in humans in the ferret model. TRS and 2009 H1N1 viruses exhibited comparable viral titers and histopathologies following virus infection and were similarly unable to transmit efficiently via respiratory droplets in the ferret model. Utilizing TRS and 2009 H1N1 viruses, we conducted extensive hematologic and blood serum analyses on infected ferrets to identify lymphohematopoietic parameters associated with mild to severe influenza virus infection. Following H1N1 or H5N1 influenza virus infection, ferrets were found to recapitulate several laboratory abnormalities previously documented with human disease, furthering the utility of the ferret model for the assessment of influenza virus pathogenicity.

  15. Expression of recombinant HA1 protein for specific detection of influenza A/H1N1/2009 antibodies in human serum.

    PubMed

    Luo, Lizhong; Nishi, Krista; Macleod, Erin; Sabara, Marta I; Coleman, Brenda L; Gubbay, Jonathan B; Li, Yan

    2013-01-01

    The hemagglutinin genes (HA1 subunit) from human and animal 2009 pandemic H1N1 virus isolates were expressed with a baculovirus vector. Recombinant HA1 (rHA1) protein-based ELISA was evaluated for detection of specific influenza A(H1N1)pdm09 antibodies in serum samples from vaccinated humans. It was found that rHA1 ELISA consistently differentiated between antibodies recognizing the seasonal influenza H1N1 and pdm09 viruses, with a concordance of 94% as compared to the hemagglutination inhibition test. This study suggests the utility of rHA1 ELISA in serosurveillance.

  16. Fatal cases associated with pandemic influenza A (H1N1) reported in Greece.

    PubMed Central

    Athanasiou, Maria; Lytras, Theodore; Spala, Georgia; Triantafyllou, Eleni; Gkolfinopoulou, Kassiani; Theocharopoulos, Georgios; Patrinos, Stavros; Danis, Kostas; Detsis, Marios; Tsiodras, Sotirios; Bonovas, Stefanos; Panagiotopoulos, Takis

    2010-01-01

    ABSTRACT Between 18 May 2009 and 3 May 2010, a total of 149 fatal cases associated with pandemic influenza A (H1N1) were reported in Greece. Detailed case-based epidemiological information was available for the large majority of fatal cases. The time distribution follows an epidemic curve with a peak in the beginning of December 2009 and a second peak one month later. This is similar to that of laboratory confirmed cases and influenza-like illness cases from our sentinel surveillance system, with two weeks delay. The most commonly reported underlying conditions were chronic cardiovascular disease and immunosuppression, while the most frequently identified risk factor was obesity. These findings should be taken into consideration, when vaccination strategies are employed. PMID:21085493

  17. Fatal 2009 pandemic influenza A (H1N1) in a bone marrow transplant recipient.

    PubMed

    Abdo, Anselmo; Alfonso, Carlos; Diaz, Guillermo; Wilford, Mario; Rocha, Maykel; Verdecia, Niurka

    2011-03-02

    Conditions characterized by immunosuppression have been recently reported as risk factors for severe novel swine-origin influenza A (H1N1) virus (S-OIV) infection during the current 2009 pandemic.  We report clinical and virological findings, antiviral therapy, and post-mortem study of S-OIV in an adult bone marrow transplant recipient. The viral genome was amplified by real time reverse transcriptase polymerase chain reaction (RT-PCR) from a nasopharyngeal swab specimen. The patient developed acute respiratory distress syndrome, septic shock, and eventually succumbed with a severe pulmonary haemorrhage. To the best of our knowledge, the entire clinical/therapy management and pathological examination in a transplant recipient infected with the S-OIV has not been previously documented. The fatal ending in this bone marrow transplant recipient supports recommendations that call for education measures, S-OIV vaccination, early diagnosis and aggressive treatment in the transplant population.

  18. Influenza a (H1N1) outbreak and challenges for pharmacotherapy.

    PubMed

    Chawla, Raman; Sharma, Rakesh Kumar; Bhardwaj, Janak Raj

    2009-01-01

    Influenza A (H1N1) virus, a genetic reassortment of endemic strain of human, avian flu and swine flu, with an inherent ability to mutate continuously has developed a subtype which is causing present flu in humans. As on 10th May, 2009, twenty nine countries are affected with officially reported 4379 cases with Mexico--1626 affected (45 deaths), US 2254 affected (02 deaths); Canada 280 (01 deaths) and Costa Ricia -8 cases (01 death) respectively. Rest of 15 countries have reported less than 100 officially confirmed cases of H1N1 infection. WHO has already declared Pandemic Alert V on 29th April, 2009. If the present flu achieves equivalent virulence to that of 1918-19 pandemic flu, expected deaths will be 62 million people. Travel advisory, stockpiling of antiviral drugs--Tamiflu & Relenza; vaccine development, activation of business continuity planning for maintenance of essential serives etc., are some of the important mitigation approaches, being followed all over the world. WHO has a regional reserve of 10,000 million doses of anti-viral drugs. National Disaster Management Authority (NDMA), Government of India, an apex body for disaster management, in active coordination with Ministry of Health & other stakeholders/service providers is maintaining a constant state of vigil on the present Influenza A (H1N1) outbreak. In collaboration with UNDMT, NDMA has outlined a strategy for Pandemic Preparedness beyond Health in April, 2008. Various non-pharmaceutical interventions like detection, isolation and quarantine are required to contain the situation. Accordingly, stockpiling of 10 million doses of anti viral drugs, surveillance at airports, isolation with strict enforcement of quarantine procedures, sustained supply of respiratory masks & other personal protective equipment; deployment of rapid response teams are some of the activities being undertaken by Indian Government proactively. As situation goes to Phase VI, there will be a shift in strategy from active

  19. 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.

  20. Predicting the antigenic structure of the pandemic (H1N1) 2009 influenza virus hemagglutinin.

    PubMed

    Igarashi, Manabu; Ito, Kimihito; Yoshida, Reiko; Tomabechi, Daisuke; Kida, Hiroshi; Takada, Ayato

    2010-01-01

    The pandemic influenza virus (2009 H1N1) was recently introduced into the human population. The hemagglutinin (HA) gene of 2009 H1N1 is derived from "classical swine H1N1" virus, which likely shares a common ancestor with the human H1N1 virus that caused the pandemic in 1918, whose descendant viruses are still circulating in the human population with highly altered antigenicity of HA. However, information on the structural basis to compare the HA antigenicity among 2009 H1N1, the 1918 pandemic, and seasonal human H1N1 viruses has been lacking. By homology modeling of the HA structure, here we show that HAs of 2009 H1N1 and the 1918 pandemic virus share a significant number of amino acid residues in known antigenic sites, suggesting the existence of common epitopes for neutralizing antibodies cross-reactive to both HAs. It was noted that the early human H1N1 viruses isolated in the 1930s-1940s still harbored some of the original epitopes that are also found in 2009 H1N1. Interestingly, while 2009 H1N1 HA lacks the multiple N-glycosylations that have been found to be associated with an antigenic change of the human H1N1 virus during the early epidemic of this virus, 2009 H1N1 HA still retains unique three-codon motifs, some of which became N-glycosylation sites via a single nucleotide mutation in the human H1N1 virus. We thus hypothesize that the 2009 H1N1 HA antigenic sites involving the conserved amino acids will soon be targeted by antibody-mediated selection pressure in humans. Indeed, amino acid substitutions predicted here are occurring in the recent 2009 H1N1 variants. The present study suggests that antibodies elicited by natural infection with the 1918 pandemic or its early descendant viruses play a role in specific immunity against 2009 H1N1, and provides an insight into future likely antigenic changes in the evolutionary process of 2009 H1N1 in the human population.

  1. Predicting the Antigenic Structure of the Pandemic (H1N1) 2009 Influenza Virus Hemagglutinin

    PubMed Central

    Igarashi, Manabu; Ito, Kimihito; Yoshida, Reiko; Tomabechi, Daisuke; Kida, Hiroshi; Takada, Ayato

    2010-01-01

    The pandemic influenza virus (2009 H1N1) was recently introduced into the human population. The hemagglutinin (HA) gene of 2009 H1N1 is derived from “classical swine H1N1” virus, which likely shares a common ancestor with the human H1N1 virus that caused the pandemic in 1918, whose descendant viruses are still circulating in the human population with highly altered antigenicity of HA. However, information on the structural basis to compare the HA antigenicity among 2009 H1N1, the 1918 pandemic, and seasonal human H1N1 viruses has been lacking. By homology modeling of the HA structure, here we show that HAs of 2009 H1N1 and the 1918 pandemic virus share a significant number of amino acid residues in known antigenic sites, suggesting the existence of common epitopes for neutralizing antibodies cross-reactive to both HAs. It was noted that the early human H1N1 viruses isolated in the 1930s–1940s still harbored some of the original epitopes that are also found in 2009 H1N1. Interestingly, while 2009 H1N1 HA lacks the multiple N-glycosylations that have been found to be associated with an antigenic change of the human H1N1 virus during the early epidemic of this virus, 2009 H1N1 HA still retains unique three-codon motifs, some of which became N-glycosylation sites via a single nucleotide mutation in the human H1N1 virus. We thus hypothesize that the 2009 H1N1 HA antigenic sites involving the conserved amino acids will soon be targeted by antibody-mediated selection pressure in humans. Indeed, amino acid substitutions predicted here are occurring in the recent 2009 H1N1 variants. The present study suggests that antibodies elicited by natural infection with the 1918 pandemic or its early descendant viruses play a role in specific immunity against 2009 H1N1, and provides an insight into future likely antigenic changes in the evolutionary process of 2009 H1N1 in the human population. PMID:20049332

  2. Characterization of H1N1 swine influenza viruses circulating in Canadian pigs in 2009.

    PubMed

    Nfon, Charles K; Berhane, Yohannes; Hisanaga, Tamiko; Zhang, Shunzhen; Handel, Katherine; Kehler, Helen; Labrecque, Olivia; Lewis, Nicola S; Vincent, Amy L; Copps, John; Alexandersen, Soren; Pasick, John

    2011-09-01

    The 2009 pandemic H1N1 (pH1N1), of apparent swine origin, may have evolved in pigs unnoticed because of insufficient surveillance. Consequently, the need for surveillance of influenza viruses circulating in pigs has received added attention. In this study we characterized H1N1 viruses isolated from Canadian pigs in 2009. Isolates from May 2009 were comprised of hemagglutinin and neuraminidase (NA) genes of classical SIV origin in combination with the North American triple-reassortant internal gene (TRIG) cassette, here termed contemporary SIV (conSIV) H1N1. These conSIV H1N1 viruses were contiguous with the North American αH1 cluster, which was distinct from the pH1N1 isolates that were antigenically more related to the γH1 cluster. After the initial isolation of pH1N1 from an Alberta pig farm in early May 2009, pH1N1 was found several times in Canadian pigs. These pH1N1 isolates were genetically and antigenically homogeneous. In addition, H1N1 viruses bearing seasonal human H1 and N1 genes together with the TRIG cassette and an NA encoding an oseltamivir-resistance marker were isolated from pigs. The NS gene of one of these seasonal human-like SIV (shSIV) H1N1 isolates was homologous to pH1N1 NS, implicating reassortment between the two strains. Antigenic cross-reactivity was observed between pH1N1 and conSIV but not with shSIV H1N1. In summary, although there was cocirculation of pH1N1 with conSIV and shSIV H1N1 in Canadian pigs after May 2009, there was no evidence supporting the presence of pH1N1 in pigs prior to May 2009. The possibility for further reassortants being generated exists and should be closely monitored.

  3. Pre-existing cross-reactive antibodies to avian influenza H5N1 and 2009 pandemic H1N1 in US military personnel.

    PubMed

    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.

  4. 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

  5. Pandemic response lessons from influenza H1N1 2009 in Asia.

    PubMed

    Fisher, Dale; Hui, David S; Gao, Zhancheng; Lee, Christopher; Oh, Myoung-Don; Cao, Bin; Hien, Tran Tinh; Patlovich, Krista; Farrar, Jeremy

    2011-08-01

    During April 2009, a novel H1N1 influenza A virus strain was identified in Mexico and the USA. Within weeks the virus had spread globally and the first pandemic of the 21st Century had been declared. It is unlikely to be the last and it is crucial that real lessons are learned from the experience. Asia is considered a hot spot for the emergence of new pathogens including past influenza pandemics. On this occasion while preparing for an avian, highly virulent influenza virus (H5N1 like) originating in Asia in fact the pandemic originated from swine, and was less virulent. This discrepancy between what was planned for and what emerged created its own challenges. The H1N1 pandemic has tested national health-care infrastructures and exposed shortcomings in our preparedness as a region. Key health challenges include communication throughout the region, surge capacity, access to reliable information and access to quality care, health-care worker skills, quality, density and distribution, access to essential medicines and lack of organizational infrastructure for emergency response. Despite years of preparation the public health and clinical research community were not ready to respond and opportunities for an immediate research response were missed. Despite warm words and pledges efforts to engage the international community to ensure equitable sharing of limited resources such as antivirals and vaccines fell short and stockpiles in the main remained in the rich world. This manuscript with authors from across the region describes some of the major challenges faced by Asia in response to the pandemic and draws lessons for the future.

  6. An update on swine-origin influenza virus A/H1N1: a review.

    PubMed

    Schnitzler, Sebastian U; Schnitzler, Paul

    2009-12-01

    Influenza viruses cause annual epidemics and occasional pandemics that have claimed the lives of millions. The emergence of new strains will continue to pose challenges to public health and the scientific communities. The recent flu pandemic caused by a swine-origin influenza virus A/H1N1 (S-OIV) presents an opportunity to examine virulence factors, the spread of the infection and to prepare for major influenza outbreaks in the future. The virus contains a novel constellation of gene segments, the nearest known precursors being viruses found in swine and it probably arose through reassortment of two viruses of swine origin. Specific markers for virulence can be evaluated in the viral genome, PB1-F2 is a molecular marker of pathogenicity but is not present in the new S-OIV. While attention was focused on a threat of an avian influenza H5N1 pandemic emerging from Asia, a novel influenza virus of swine origin emerged in North America, and is now spreading worldwide. However, S-OIV demonstrates that even serotypes already encountered in past human pandemics may constitute new pandemic threats. There are concerns that this virus may mutate or reassort with existing influenza viruses giving rise to more transmissible or more pathogenic viruses. The 1918 Spanish flu pandemic virus was relatively mild in its first wave and acquired more virulence when it returned in the winter. Thus preparedness on a global scale against a potential more virulent strain is highly recommended. Most isolates of the new S-OIVs are susceptible to neuraminidase inhibitors, and currently a vaccine against the pandemic strain is being manufactured and will be available this fall. This review summarizes the current information on the new pandemic swine-origin influenza virus A/H1N1.

  7. Association of 2009 Pandemic Influenza A (H1N1) Infection and Increased Hospitalization With Parapneumonic Empyema in Children in Utah

    PubMed Central

    Ampofo, Krow; Herbener, Amy; Blaschke, Anne J.; Heyrend, Caroline; Poritz, Mark; Korgenski, Kent; Rolfs, Robert; Jain, Seema; Carvalho, Maria da Glória; Pimenta, Fabiana C.; Daly, Judy; Mason, Edward O.; Byington, Carrie L.; Pavia, Andrew T.

    2011-01-01

    Background During previous influenza pandemics, many deaths were associated with secondary bacterial infection. In April 2009, a previously unknown 2009 influenza A virus (2009 H1N1) emerged, causing a global influenza pandemic. We examined the relationship between circulating 2009 H1N1 and the occurrence of secondary bacterial parapneumonic empyema in children. Methods Children hospitalized with parapneumonic empyema from August 2004 to July 2009, including a period when the 2009 H1N1 circulated in Utah, were identified using International Classification of Diseases, Ninth Revision codes. We compared the average number of children diagnosed with influenza A and the number of admissions for empyema per month for the previous 4 seasons to rates of empyema during the 2009 H1N1 outbreak. We identified causative bacteria using culture and polymerase chain reaction (PCR). Results We observed an increase in hospitalization of children with pneumonia complicated by empyema during a severe outbreak of 2009 H1N1 during the spring and summer of 2009, compared with historical data for the previous 4 seasons. Streptococcus pneumoniae and Streptococcus pyogenes were the predominant bacteria identified. Conclusions Similar to previous pandemics, secondary bacterial infection with S. pneumoniae and S. pyogenes were associated with the 2009 H1N1 outbreak. There is an urgent need to better understand bacterial complications of pandemic influenza. In the interim, influenza vaccines, antiviral agents, and pneumococcal vaccines should be used to prevent cases of secondary bacterial pneumonia whenever possible. PMID:20407400

  8. H1N1 Flu & U.S. Schools: Answers to Frequently Asked Questions

    ERIC Educational Resources Information Center

    US Department of Education, 2009

    2009-01-01

    A severe form of influenza known as H1N1, commonly being called swine flu, has health officials around the world concerned. In the United States, the outbreak of H1N1 has prompted school closures and cancellation of school-related events. As the flu spreads, the Department of Education encourages school leaders, parents and students to know how to…

  9. Adoption of Preventive Measures and Attitudes toward the H1N1 Influenza Pandemic in Schools

    ERIC Educational Resources Information Center

    Pérez, Anna; Rodríguez, Tània; López, Maria José; Continente, Xavier; Nebot, Manel

    2016-01-01

    Background: This study describes the perceived impact of H1N1 influenza and the adoption of the recommended measures to address the pandemic in schools. Methods: A cross-sectional self-reported survey was conducted in 433 schools in Barcelona addressed to the school principal or the H1N1 influenza designated person. A descriptive analysis was…

  10. Generalized anhidrosis in a child following presumptive H1N1 influenza.

    PubMed

    Ghosh, Partha S; Mitra, Sudeshna; Fealey, Robert D

    2012-04-01

    We report an 8-year-old girl who developed generalized anhidrosis following presumptive H1N1 infection. Pure autonomic dysfunction is an unusual complication following H1N1 infection and specially generalized anhidrosis without other autonomic dysfunction have not been reported before.

  11. Novel route of exposure explains outbreaks of pH1N1 influenza in turkeys

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The presence of avian and swine influenza virus genes in the 2009 novel H1N1 pandemic virus (pH1N1) raises the potential for infection in poultry following exposure to infected humans or swine. This is especially true for turkeys because of their known susceptibility to type A influenza viruses and...

  12. Absence of Pandemic H1N1 Influenza A Virus in Fresh Pork

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Pigs experimentally infected with pandemic 2009 H1N1 influenza A virus developed respiratory disease; however, there was no evidence for systemic disease to suggest that pork from pigs infected with H1N1 influenza would contain infectious virus. These findings support the WHO recommendation that po...

  13. Isolation and characterization of pandemic H1N1 influenza viruses in pigs in Brazil

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Influenza A virus (IAV) infections are endemic diseases in pork producing countries around the world. The emergence of the pandemic 2009 human H1N1 influenza A virus (pH1N1) raised questions about the occurrence of this virus in Brazilian swine populations. During a 2009-2010 swine influenza virus r...

  14. Susceptibility of turkeys to pandemic H1N1 virus by reproductive tract insemination

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Beginning in April 2009, cases of acute respiratory disease were reported in humans caused by a novel H1N1 influenza A virus (pH1N1) in Mexico which has since spread globally in the human population and been declared a pandemic. Initial studies using intranasal route of inoculation failed to produc...

  15. Susceptibility of poultry to pandemic (H1N1) 2009 virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Beginning in April 2009, cases of acute respiratory disease were reported in humans caused by a novel H1N1 influenza A virus in Mexico. The causative agent was complex reassortant influenza A virus with gene segments from North American classic H1N1 swine viruses, North American avian viruses, huma...

  16. Rapid differentiation of seasonal and pandemic H1N1 influenza through proteotyping of viral neuraminidase with mass spectrometry.

    PubMed

    Schwahn, Alexander B; Wong, Jason W H; Downard, Kevin M

    2010-06-01

    Signature peptides of the neuraminidase antigen across all common circulating human subtypes of type A and B influenza are identified through the bioinformatic alignment of translated gene sequences. The detection of these peptides within the high-resolution mass spectra of whole antigen, virus, and vaccine digests enables the strains to be rapidly and directly typed and subtyped. Importantly, unique signature peptides for pandemic (H1N1) 2009 influenza are identified and detected that enable pandemic strains to be rapidly and directly differentiated from seasonal type A (H1N1) influenza strains. The detection of these peptides can enable the origins of the neuraminidase gene to be monitored in the case of reassorted strains.

  17. Initial psychological responses to Influenza A, H1N1 ("Swine flu")

    PubMed Central

    2009-01-01

    Background 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. Methods 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 Results 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. Conclusion Initial responses to Influenza A

  18. Antigenic drift of the pandemic 2009 A(H1N1) influenza virus in A ferret model.

    PubMed

    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.

  19. Epidemiology of pandemic H1N1 strains in a tertiary hospital of Maharashtra.

    PubMed

    Shrikhande, Sunanda; Bhoyar, S K; Tenpe, S H; Deogade, N G

    2012-01-01

    Swine-flu is a viral fever caused by a new mutated strain Influenza A virus subtype H1N1, which infects humans. Pandemic H1N1 (pH1N1/2009) virus was detected in the first quarter of 2009 in the west coastal region of North America and spread very rapidly to the other countries during April-June, 2009. This study was conducted to assess the epidemiology of pandemic H1N1 strains using a cross-sectional study design in a tertiary hospital. The symptomatic patients attending the flu outpatient department (OPD)/emergency from August 2009 to April 2011 at Indira Gandhi Government Medical College, Nagpur were included using a standard case definition. A total of 67 (27.01%) samples from 247 patients were pandemic influenza A/H1N1 positive. None of the patients had a history of foreign travel, whereas 23.88% of the patients gave history of travel to an endemic area. Overall, 22.38% of the patients came in contact with proven cases of pandemic H1N1. pH1N1 transmission activity has increased since May 2010.

  20. 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.

  1. Serological Evidence of Pandemic H1N1 Influenza Virus Infections in Greek Swine.

    PubMed

    Kyriakis, C S; Papatsiros, V G; Athanasiou, L V; Valiakos, G; Brown, I H; Simon, G; Van Reeth, K; Tsiodras, S; Spyrou, V; Billinis, C

    2016-08-01

    The introduction of the 2009 pandemic H1N1 (pH1N1) influenza virus in pigs changed the epidemiology of influenza A viruses (IAVs) in swine in Europe and the rest of the world. Previously, three IAV subtypes were found in the European pig population: an avian-like H1N1 and two reassortant H1N2 and H3N2 viruses with human-origin haemagglutinin (HA) and neuraminidase proteins and internal genes of avian decent. These viruses pose antigenically distinct HAs, which allow the retrospective diagnosis of infection in serological investigations. However, cross-reactions between the HA of pH1N1 and the HAs of the other circulating H1 IAVs complicate serological diagnosis. The prevalence of IAVs in Greek swine has been poorly investigated. In this study, we examined and compared haemagglutination inhibition (HI) antibody titres against previously established IAVs and pH1N1 in 908 swine sera from 88 herds, collected before and after the 2009 pandemic. While we confirmed the historic presence of the three IAVs established in European swine, we also found that 4% of the pig sera examined after 2009 had HI antibodies only against the pH1N1 virus. Our results indicate that pH1N1 is circulating in Greek pigs and stress out the importance of a vigorous virological surveillance programme.

  2. Adoption of preventive behaviors in response to the 2009 H1N1 influenza pandemic: a multiethnic perspective

    PubMed Central

    SteelFisher, Gillian K; Blendon, Robert J; Kang, Minah; Ward, Johanna R M; Kahn, Emily B; Maddox, Kathryn EW; Lubell, Keri M; Tucker, Myra; Ben-Porath, Eran N

    2015-01-01

    Background As public health leaders prepare for possible future influenza pandemics, the rapid spread of 2009 H1N1 influenza highlights the need to focus on measures the public can adopt to help slow disease transmission. Such measures may relate to hygiene (e.g., hand washing), social distancing (e.g., avoiding places where many people gather), and pharmaceutical interventions (e.g., vaccination). Given the disproportionate impact of public health emergencies on minority communities in the United States, it is important to understand whether there are differences in acceptance across racial/ethnic groups that could lead to targeted and more effective policies and communications. Objectives This study explores racial/ethnic differences in the adoption of preventive behaviors during the 2009 H1N1 influenza pandemic. Patients/Methods Data are from a national telephone poll conducted March 17 to April 11, 2010, among a representative sample of 1123 white, 330 African American, 317 Hispanic, 268 Asian, and 262 American Indian/Alaska Native adults in the USA. Results People in at least one racial/ethnic minority group were more likely than whites to adopt several behaviors related to hygiene, social distancing, and healthcare access, including increased hand washing and talking with a healthcare provider (P-values <0·05). Exceptions included avoiding others with influenza-like illnesses and receiving 2009 H1N1 and seasonal influenza vaccinations. After we controlled the data for socioeconomic status, demographic factors, healthcare access, and illness- and vaccine-related attitudes, nearly all racial/ethnic differences in behaviors persisted. Conclusions Minority groups appear to be receptive to several preventive behaviors, but barriers to vaccination are more pervasive. PMID:25688806

  3. Transplantation of solid organs procured from influenza A H1N1 infected donors.

    PubMed

    Cockbain, Andrew J; Jacob, Matthew; Ecuyer, Clare; Hostert, Lutz; Ahmad, Niaz

    2011-12-01

    Following the influenza A H1N1 (swine flu) pandemic, there remains little evidence informing the safety of transplanting organs from donors suspected or diagnosed with H1N1. Limited guidelines from the major transplant societies leave the use of such organs at the discretion of individual transplant centres, and practice varies considerably both nationally and internationally. We present the largest published series of outcome following transplantation of organs from H1N1 positive donors and demonstrate that these organs can be transplanted safely and with good short-term outcome. We discuss our local policy for treatment of recipients with Oseltamivir.

  4. [Virological characteristics of pandemic (H1N1) 2009 influenza virus].

    PubMed

    Horimoto, Taisuke; Yamada, Shinya; Kawaoka, Yoshihiro

    2010-06-01

    In the spring of 2009, a novel swine-origin H1N1 virus, whose antigenicity is quite different from those of seasonal human H1N1 strains, emerged in Mexico and readily transmitted and spread among humans, resulting in the first influenza pandemic in the 21st century. This novel H1N1 virus was shown to be a triple reassortant comprising genes derived from avian, human, and swine viruses. Here, we review our current knowledge of this pandemic influenza virus and discuss future aspects of the pandemic.

  5. 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.

  6. From where did the 2009 'swine-origin' influenza A virus (H1N1) emerge?

    PubMed

    Gibbs, Adrian J; Armstrong, John S; Downie, Jean C

    2009-11-24

    The swine-origin influenza A (H1N1) virus that appeared in 2009 and was first found in human beings in Mexico, is a reassortant with at least three parents. Six of the genes are closest in sequence to those of H1N2 'triple-reassortant' influenza viruses isolated from pigs in North America around 1999-2000. Its other two genes are from different Eurasian 'avian-like' viruses of pigs; the NA gene is closest to H1N1 viruses isolated in Europe in 1991-1993, and the MP gene is closest to H3N2 viruses isolated in Asia in 1999-2000. The sequences of these genes do not directly reveal the immediate source of the virus as the closest were from isolates collected more than a decade before the human pandemic started. The three parents of the virus may have been assembled in one place by natural means, such as by migrating birds, however the consistent link with pig viruses suggests that human activity was involved. We discuss a published suggestion that unsampled pig herds, the intercontinental live pig trade, together with porous quarantine barriers, generated the reassortant. We contrast that suggestion with the possibility that laboratory errors involving the sharing of virus isolates and cultured cells, or perhaps vaccine production, may have been involved. Gene sequences from isolates that bridge the time and phylogenetic gap between the new virus and its parents will distinguish between these possibilities, and we suggest where they should be sought. It is important that the source of the new virus be found if we wish to avoid future pandemics rather than just trying to minimize the consequences after they have emerged. Influenza virus is a very significant zoonotic pathogen. Public confidence in influenza research, and the agribusinesses that are based on influenza's many hosts, has been eroded by several recent events involving the virus. Measures that might restore confidence include establishing a unified international administrative framework coordinating

  7. Pediatric Healthcare Response to Pandemic (H1N1) 2009 Influenza Stakeholder Meeting - Summary of Proceedings

    SciTech Connect

    HCTT CHE

    2010-01-01

    The goal of the meeting was to bring together subject matter experts to develop tools and resources for use by the pediatric healthcare community in response to 2009 (H1N1) pandemic influenza activity during the 2009 influenza season.

  8. Structural Basis of Preexisting Immunity to the 2009 H1N1 Pandemic Influenza Virus

    SciTech Connect

    Xu, Rui; Ekiert, Damian C.; Krause, Jens C.; Hai, Rong; Crowe, Jr., James E.; Wilson, Ian A.

    2010-05-25

    The 2009 H1N1 swine flu is the first influenza pandemic in decades. The crystal structure of the hemagglutinin from the A/California/04/2009 H1N1 virus shows that its antigenic structure, particularly within the Sa antigenic site, is extremely similar to those of human H1N1 viruses circulating early in the 20th century. The cocrystal structure of the 1918 hemagglutinin with 2D1, an antibody from a survivor of the 1918 Spanish flu that neutralizes both 1918 and 2009 H1N1 viruses, reveals an epitope that is conserved in both pandemic viruses. Thus, antigenic similarity between the 2009 and 1918-like viruses provides an explanation for the age-related immunity to the current influenza pandemic.

  9. Measurement of Swine H1N1 Hemagglutinin Peptide binding with Piezoresistive Microcantilever Arrays

    SciTech Connect

    Bajwa, Navdeep K; Maldonado, Carlos J.; Thundat, Thomas George; Passian, Ali

    2014-03-24

    The effective detection of Swine H1N1 Hemagglutinin peptide is crucial as it could be used as a positive control to screen for highly infectious flu strains such as Swine-Origin Influenza A (H1N1). Piezoresistive microcantilever arrays present a pathway towards highly sensitive and label-free detection of biomolecules by transducing the antigen-antibody binding into change in resistivity via induced surface stress variation. We also demonstrate a mechanical transduction of Swine H1N1 Hemagglutinin peptide binding and suggest the employed technique may offer a potential platform for detection of the H1N1 virus, which could be clinically used to diagnose and provide subsequent relief.

  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. Piezoresistive measurement of Swine H1N1 Hemagglutinin peptide binding with microcantilever arrays

    NASA Astrophysics Data System (ADS)

    Bajwa, N.; Maldonado, C. J.; Thundat, T.; Passian, A.

    2014-03-01

    Effective detection of Swine H1N1 Hemagglutinin peptide is crucial as it could be used as a positive control to screen for highly infectious flu strains such as Swine-Origin Influenza A (H1N1). Piezoresistive microcantilever arrays present a pathway towards highly sensitive and label-free detection of biomolecules by transducing the antigen-antibody binding into change in resistivity via induced surface stress variation. We demonstrate a mechanical transduction of Swine H1N1 Hemagglutinin peptide binding and suggest the employed technique may offer a potential platform for detection of the H1N1 virus, which could be clinically used to diagnose and provide subsequent relief.

  12. Structural basis of preexisting immunity to the 2009 H1N1 pandemic influenza virus.

    PubMed

    Xu, Rui; Ekiert, Damian C; Krause, Jens C; Hai, Rong; Crowe, James E; Wilson, Ian A

    2010-04-16

    The 2009 H1N1 swine flu is the first influenza pandemic in decades. The crystal structure of the hemagglutinin from the A/California/04/2009 H1N1 virus shows that its antigenic structure, particularly within the Sa antigenic site, is extremely similar to those of human H1N1 viruses circulating early in the 20th century. The cocrystal structure of the 1918 hemagglutinin with 2D1, an antibody from a survivor of the 1918 Spanish flu that neutralizes both 1918 and 2009 H1N1 viruses, reveals an epitope that is conserved in both pandemic viruses. Thus, antigenic similarity between the 2009 and 1918-like viruses provides an explanation for the age-related immunity to the current influenza pandemic.

  13. Akt inhibitor MK2206 prevents influenza pH1N1 virus infection in vitro.

    PubMed

    Denisova, Oxana V; Söderholm, Sandra; Virtanen, Salla; Von Schantz, Carina; Bychkov, Dmitrii; Vashchinkina, Elena; Desloovere, Jens; Tynell, Janne; Ikonen, Niina; Theisen, Linda L; Nyman, Tuula A; Matikainen, Sampsa; Kallioniemi, Olli; Julkunen, Ilkka; Muller, Claude P; Saelens, Xavier; Verkhusha, Vladislav V; Kainov, Denis E

    2014-07-01

    The influenza pH1N1 virus caused a global flu pandemic in 2009 and continues manifestation as a seasonal virus. Better understanding of the virus-host cell interaction could result in development of better prevention and treatment options. Here we show that the Akt inhibitor MK2206 blocks influenza pH1N1 virus infection in vitro. In particular, at noncytotoxic concentrations, MK2206 alters Akt signaling and inhibits endocytic uptake of the virus. Interestingly, MK2206 is unable to inhibit H3N2, H7N9, and H5N1 viruses, indicating that pH1N1 evolved specific requirements for efficient infection. Thus, Akt signaling could be exploited further for development of better therapeutics against pH1N1 virus.

  14. H1N1-Induced Venous Thromboembolic Events? Results of a Single-Institution Case Series

    PubMed Central

    Dimakakos, Evangelos; Vathiotis, Ioannis; Papaspiliou, Aggeliki; Panagiotarakou, Meropi; Manolis, Emmanouil; Syrigos, Konstantinos

    2016-01-01

    We describe the clinical and imaging characteristics of 7 cases with polymerase chain reaction-confirmed novel influenza A H1N1 virus (pH1N1) infection who developed venous thromboembolic events (VTEs) while being hospitalized for influenza pneumonia. Pulmonary embolism (PE) without deep vein thrombosis (DVT) was observed in 6 of 7 cases (85.7%); PE with underlying DVT was found in 1 patient (14.3%). PMID:28018924

  15. Oseltamivir-Resistant Pandemic (H1N1) 2009 Virus, Mexico

    PubMed Central

    Ramirez-Gonzalez, José Ernesto; Gonzalez-Duran, Elizabeth; Alcantara-Perez, Patricia; Wong-Arambula, Claudia; Olivera-Diaz, Hiram; Cortez-Ortiz, Iliana; Barrera-Badillo, Gisela; Nguyen, Ha; Gubareva, Larisa; Lopez-Martinez, Irma; Díaz-Quiñonez, Jose Alberto; Lezana-Fernández, Miguel Angel; Gatell-Ramírez, Hugo Lopez; Villalobos, Jose Angel Cordova; Hernández-Avila, Mauricio

    2011-01-01

    During May 2009–April 2010, we analyzed 692 samples of pandemic (H1N1) 2009 virus from patients in Mexico. We detected the H275Y substitution of the neuraminidase gene in a specimen from an infant with pandemic (H1N1) 2009 who was treated with oseltamivir. This virus was susceptible to zanamivir and resistant to adamantanes and oseltamivir. PMID:21291607

  16. 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

  17. Experience of influenza A H1N1 in a paediatric emergency unit.

    PubMed

    Biçer, Suat; Ercan Sariçoban, Hülya; Özen, Ahmet Oğuzhan; Saf, Coşkun; Ergenekon Ulutaş, Pinar; Gürol, Yeşim; Yilmaz, Gülden; Vitrinel, Ayça; Özelgün, Berna

    2015-06-01

    This study was carried out to evaluate symptoms, clinical findings, treatment options and complications of H1N1 influenza infection in patients who applied to our emergency unit during the influenza season in 2009. The clinical and laboratory findings of children with influenza A (H1N1) during the influenza season in 2009 were evaluated retrospectively. Influenza A was diagnosed by polymerase chain reaction and/or rapid antigen test. Clinical and laboratory findings of the patients with H1N1 (group I) and without H1N1 (group II) were compared. Fever and myalgia were noted to be higher in group I (p <0.05). The mean body temperature in group I was 39.0?, which was statistically different from group II (p <0.001). Myalgia was observed only in group I (15.4%), but not in group II (p <0.05). There were three patients with diarrhoea, two of whom were in group I, and they had no significant respiratory symptoms. Lymphopenia was seen in 18 patients (81.8%) in group I and in four patients (23.5%) in group II (p <0.05). Oseltamivir treatment was applied to 28 patients, where 24 had severe symptoms, nine had comorbid factors and two did not have any of these. The fever was higher in group I and myalgia was present only in group I. In group I, the lymphocyte count was significantly lower than in group II. The fever was higher in patients of H1N1 (average of 39°C) and myalgia was present only in patients with H1N1. The lymphocyte count was significantly lower in patients with H1N1 than those without H1N1. While none of the patients required intensive care, three patients requiring hospitalization were discharged after referral and completion of their treatment.

  18. Influenza A(H1N1)pdm09 virus in pigs, Réunion Island.

    PubMed

    Cardinale, Eric; Pascalis, Hervé; Temmam, Sarah; Hervé, Séverine; Saulnier, Aure; Turpin, Magali; Barbier, Nicolas; Hoarau, Johny; Quéguiner, Stéphane; Gorin, Stéphane; Foray, Coralie; Roger, Matthieu; Porphyre, Vincent; André, Paul; Thomas, Thierry; de Lamballerie, Xavier; Dellagi, Koussay; Simon, Gaëlle

    2012-10-01

    During 2009, pandemic influenza A(H1N1)pdm09 virus affected humans on Réunion Island. Since then, the virus has sustained circulation among local swine herds, raising concerns about the potential for genetic evolution of the virus and possible retransmission back to humans of variants with increased virulence. Continuous surveillance of A(H1N1)pdm09 infection in pigs is recommended.

  19. Clinical Presentation of Novel Influenza A (H1N1) in Hospitalized Children

    PubMed Central

    Soleimani, Gholamreza; Akbarpour, Marzieh

    2011-01-01

    Objective Human pandemic influenza H1N1 virus as the cause of febrile respiratory infection ranging from self-limited to severe illness has spread globally during 2009. Signs and symptoms of upper and lower respiratory tract involvement, fever, sore throat, rhinitis, myalgia, malaise, headache, chills and fatigue are common. In this article we report the clinical presentation of Influenza A (H1N1) in our hospitalized children. Methods Between September and October 2009, all children requiring hospitalization for suspected H1N1 infection were transferred to Pediatric Infectious Diseases ward. For all patients the throat swab was taken for PCR testing to confirm or exclude the diagnosis of H1N1 Influenza A. Case patients consisted of H1N1-positive patients. Age, sex, symptoms, signs, laboratory data, CXR changes, details of therapy, duration of admission and patient outcome were documented. Findings Twenty patients were H1N1 positive. Mean age of the patients was 65.50±9.8 months. Fever and coughs were with 55% the most commonly reported symptoms. Other presentations included vomiting (55%), abdominal pain (25%), cyanosis and dyspnea (5%), body ache (40%), rhinorrhea (80%), sore throat (35%), head stiffness (5%) and loss of conciousness (5%). The median temperature of the patients was 38.5°C. Chest X-Ray changes were noted in 13 out of 20 patients (65%). Mean leukocyte and platelet was 6475 and 169000 respectively. Seventeen (85%) patients were treated with Oseltamivir, 3 patients received adjuvant antibiotics. The mean duration of admission was 3 days. Three patients required intensive care support and all of them expired due to superinfection. Conclusion Our data confirm that the presentation of influenza in children is variable and 2009 H1N1 influenza may cause leucopenia and thrombocytopenia. PMID:23056790

  20. 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.

  1. Framing of Influenza A (H1N1) pandemic in a Singaporean newspaper.

    PubMed

    Basnyat, Iccha; Lee, Seow Ting

    2015-12-01

    This study seeks to understand how public health messages provided by the government in Singapore during an Influenza A (H1N1) pandemic were framed by the news media for the public. News articles were analyzed to explore how the global pandemic was framed as a local event, providing a unique exploration of the dynamic involving public health communication, news media and the state. Thematic analysis (n = 309) included the government-issued press releases disseminating public health information about H1N1 that were directly linked to news stories (n = 56) and news stories about H1N1 generated by the newspaper (n = 253). Four themes were found: (i) imported disease, (ii) war/battle metaphors, (iii) social responsibility and (iv) lockdown policies. Frame analysis revealed that the news coverage during the H1N1 pandemic reflected how the newspaper framed and mediated the information flow, amplified a positive tone for the government response, emphasized individual responsibility and utilized gain frames to construct local messages about the global H1N1 pandemic that reified Singapore as a nation-state.

  2. Illinois department of public health H1N1/A pandemic communications evaluation survey.

    SciTech Connect

    Walsh, D.; Decision and Information Sciences

    2010-09-16

    Because of heightened media coverage, a 24-hour news cycle and the potential miscommunication of health messages across all levels of government during the onset of the H1N1 influenza outbreak in spring 2009, the Illinois Department of Public Health (IDPH) decided to evaluate its H1N1 influenza A communications system. IDPH wanted to confirm its disease information and instructions were helping stakeholders prepare for and respond to a novel influenza outbreak. In addition, the time commitment involved in preparing, issuing, monitoring, updating, and responding to H1N1 federal guidelines/updates and media stories became a heavy burden for IDPH staff. The process and results of the H1N1 messaging survey represent a best practice that other health departments and emergency management agencies can replicate to improve coordination efforts with stakeholder groups during both emergency preparedness and response phases. Importantly, the H1N1 survey confirmed IDPH's messages were influencing stakeholders decisions to activate their pandemic plans and initiate response operations. While there was some dissatisfaction with IDPH's delivery of information and communication tools, such as the fax system, this report should demonstrate to IDPH that its core partners believe it has the ability and expertise to issue timely and accurate instructions that can help them respond to a large-scale disease outbreak in Illinois. The conclusion will focus on three main areas: (1) the survey development process, (2) survey results: best practices and areas for improvement and (3) recommendations: next steps.

  3. Initial incursion of pandemic (H1N1) 2009 influenza A virus into European pigs.

    PubMed

    Welsh, M D; Baird, P M; Guelbenzu-Gonzalo, M P; Hanna, A; Reid, S M; Essen, S; Russell, C; Thomas, S; Barrass, L; McNeilly, F; McKillen, J; Todd, D; Harkin, V; McDowell, S; Choudhury, B; Irvine, R M; Borobia, J; Grant, J; Brown, I H

    2010-05-22

    The initial incursion of pandemic (H1N1) 2009 influenza A virus (pH1N1) into a European pig population is reported. Diagnosis of swine influenza caused by pandemic virus was made during September 2009 following routine submission of samples for differential diagnosis of causative agents of respiratory disease, including influenza A virus. All four pigs (aged six weeks) submitted for investigation from a pig herd of approximately 5000 animals in Northern Ireland, experiencing acute-onset respiratory signs in finishing and growing pigs, were positive by immunofluorescence for influenza A. Follow-up analysis of lung tissue homogenates by real-time RT-PCR confirmed the presence of pH1N1. The virus was subsequently detected on two other premises in Northern Ireland; on one premises, detection followed the pre-export health certification testing of samples from pigs presumed to be subclinically infected as no clinical signs were apparent. None of the premises was linked to another epidemiologically. Sequencing of the haemagglutinin and neuraminidase genes revealed high nucleotide identity (>99.4 per cent) with other pH1N1s isolated from human beings. Genotypic analyses revealed all gene segments to be most closely related to those of contemporary pH1N1 viruses in human beings. It is concluded that all three outbreaks occurred independently, potentially as a result of transmission of the virus from human beings to pigs.

  4. Emergence and characterisation of pandemic H1N1 influenza viruses in Hungarian swine herds.

    PubMed

    Bálint, Adám; Kiss, István; Bányai, Krisztián; Biksi, Imre; Szentpáli-Gavallér, Katalin; Magyar, Tibor; Jankovics, István; Rózsa, Mónika; Szalai, Bálint; Takács, Mária; Tóth, Adám György; Dán, Adám

    2013-03-01

    In 2010, two novel porcine H1N1 influenza viruses were isolated from pigs with influenza-like illness in Hungarian swine herds. Sequence and phylogenetic analysis of these strains revealed that they shared molecular features with the pandemic H1N1 influenza virus strains, which emerged globally during 2009. The PB2, HA and NA genes contained unique amino acid changes compared to the available new H1N1 influenza virus sequences of pig origin. Furthermore, the investigated strains could be separated with respect to parallel amino acid substitutions affecting the polymerase genes (PB2, PB1 and PA) and the nucleoprotein (NP) gene, supporting the proposed complementarities between these proteins, all required for the viral fitness. Molecular characterisation of two Hungarian human pandemic H1N1 isolates was also performed, so that we could compare contemporaneous strains of different host species origins. Shared molecular motifs in various genes of animal and human influenza strains suggested that the Hungarian porcine strains could have originated from humans through direct interspecies transmission. This study is among the few that support the natural human-to-pig transmission of the pandemic H1N1 influenza virus.

  5. Tracking the 2009 H1N1 influenza virus in the Italian region Campania.

    PubMed

    Esposito, Ciro; Di Spirito, Antimo; Cuomo, Nunzia; Di Nicuolo, Giuseppe; Flaminio, Giovanni; Altamura, Fabiana; Ambrosino, Daniele; Cantalupo, Federich; Costa, Caterina; Pentimalli, Francesca; Tarro, Giulio

    2012-07-01

    A novel swine-origin influenza A (H1N1) virus affecting humans was detected in April 2009 in Mexico, Canada, and USA. The S-OIV infection caused a mild to severe febrile respiratory disease throughout the world. Here, we briefly review the main features of influenza A viruses, which caused also other pandemics in the past, and focus in particular on the epidemiology data of the H1N1 influenza in the Italian region Campania, which resulted the most affected by the S-OIV and the one with more lethal cases. In Campania, the peak of influenza preceded of about 2 weeks the incidence peak at the national level. Moreover, the percentage of H1N1-positive patients was much higher in the main town Naples, compared to the other Campania provinces. The age group from 7 months to 17 years was the most affected by the H1N1 infection (43.45%), similarly to what reported at the national level. Here, we discuss the possible reasons of the high H1N1 incidence in Campania and the implications that these findings could have on the future prevention campaigns.

  6. Outcome of pandemic H1N1 infections in hematopoietic stem cell transplant recipients

    PubMed Central

    Ljungman, Per; de la Camara, Rafael; Perez-Bercoff, Lena; Abecasis, Manuel; Nieto Campuzano, Jose Bartolo; Cannata-Ortiz, M. Jimena; Cordonnier, Catherine; Einsele, Hermann; Gonzalez-Vicent, Marta; Espigado, Ildefonso; Halter, Jörg; Martino, Rodrigo; Mohty, Bilal; Sucak, Gülsan; Ullmann, Andrew J; Vázquez, Lourdes; Ward, Katherine N.; Engelhard, Dan

    2011-01-01

    During 2009, a new strain of A/H1N1 influenza appeared and became pandemic. A prospective study was performed to collect data regarding risk factors and outcome of A/H1N1 in hematopoietic stem cell transplant recipients. Only verified pandemic A/H1N1 influenza strains were included: 286 patients were reported, 222 allogeneic and 64 autologous recipients. The median age was 38.3 years and the median time from transplant was 19.4 months. Oseltamivir was administered to 267 patients and 15 patients received zanamivir. One hundred and twenty-five patients (43.7%) were hospitalized. Ninety-three patients (32.5%) developed lower respiratory tract disease. In multivariate analysis, risk factors were age (OR 1.025; 1.01–1.04; P=0.002) and lymphopenia (OR 2.49; 1.33–4.67; P<0.001). Thirty-three patients (11.5%) required mechanical ventilation. Eighteen patients (6.3%) died from A/H1N1 infection or its complications. Neutropenia (P=0.03) and patient age (P=0.04) were significant risk factors for death. The 2009 A/H1N1 influenza pandemic caused severe complications in stem cell transplant recipients. PMID:21546495

  7. Prophylaxis and therapy of pandemic H1N1 virus infection using egg yolk antibody.

    PubMed

    Yang, Yuan-e; Wen, Junlin; Zhao, Suqing; Zhang, Kun; Zhou, Yingliang

    2014-09-01

    Influenza A virus infects the human respiratory system and causes acute and fatal pulmonary diseases. The emergence of drug-resistant viral strains highlights the need for alternative therapeutic approaches. In this work, IgY antibody was raised in immunized laying hens, and its antiviral activity was evaluated in the context of passive immunization. With inactivated whole H1N1 virus, high-titer IgY antibody 9.18 mg/mL egg yolk was induced by the eighth week after immunization. Western blotting and the hemagglutination inhibition (HI) test demonstrated that the IgY antibody could specifically bind the neuraminidase and hemagglutinin of the H1N1 virus. In the plaque reduction assay, the IgY antibody reduced the H1N1 viral infection in MDCK (Madin-Darby canine kidney) cells. In a mouse model, the anti-H1N1 IgY antibody exhibited in vivo protection by reducing the infectious titer of the virus in the lung while maintaining the weight and normal structure of the lung tissue. Additionally, the anti-H1N1 IgY antibody exhibited protective activity comparable to the neuraminidase inhibitor oseltamivir. These results demonstrated that IgY can be easily produced and can offers an effective alternative approach for influenza control.

  8. Influenza A(H1N1)pdm09 during air travel.

    PubMed

    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

    2013-01-01

    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.

  9. Prevalence of Diabetes in the 2009 Influenza A (H1N1) and the Middle East Respiratory Syndrome Coronavirus: A Systematic Review and Meta-Analysis

    PubMed Central

    Badawi, Alaa; Ryoo, Seung Gwan

    2016-01-01

    and ~300 MERS-CoV cases indicated an overall prevalence of 14.6% and 54.4% for diabetes in H1N1 and MERS-CoV cases, respectively. This may suggest a possible etiological relationship between diabetes and each of the two infectious conditions. Introduction of effective public health vaccination intervention strategies against severe acute respiratory infections should be developed to target subjects with chronic disorders such as diabetes, obesity and cardiovascular conditions. PMID:28083520

  10. Novel swine-origin influenza virus A (H1N1): the first pandemic of the 21st century.

    PubMed

    Chang, Luan-Yin; Shih, Shin-Ru; Shao, Pei-Lan; Huang, Daniel Tsung-Ning; Huang, Li-Min

    2009-07-01

    An influenza epidemic was detected in April 2009 at the border between the United States and Mexico. The virus was identified soon after to be a swine-origin influenza virus A (S-OIV A) (H1N1). This virus has an HA gene that is derived from the 1918 swine influenza virus and other genes from human, avian, and Eurasian swine influenza viruses. Clinically, it behaves similarly to seasonal influenza. The only differentiating characteristics are vomiting and diarrhea in a quarter of infected patients, which are rare in seasonal influenza. On June 11, 2009, the World Health Organization declared the first pandemic of the 21st century, caused by S-OIV A (H1N1). Vaccination is the only way to dampen this pandemic. Many questions await answers, including the clinical impact of the pandemic, optimal doses of vaccine, and the future destiny of the virus. A breakthrough in vaccinology against influenza is needed to address the recurring influenza pandemic.

  11. Critical care services and the H1N1 (2009) influenza epidemic in Australia and New Zealand in 2010: the impact of the second winter epidemic

    PubMed Central

    2011-01-01

    Introduction During the first winter of exposure, the H1N1 2009 influenza virus placed considerable strain on intensive care unit (ICU) services in Australia and New Zealand (ANZ). We assessed the impact of the H1N1 2009 influenza virus on ICU services during the second (2010) winter, following the implementation of vaccination. Methods A prospective, cohort study was conducted in all ANZ ICUs during the southern hemisphere winter of 2010. Data on demographic and clinical characteristics, including vaccination status and outcomes, were collected. The characteristics of patients admitted during the 2010 and 2009 seasons were compared. Results From 1 June to 15 October 2010, there were 315 patients with confirmed influenza A, of whom 283 patients (90%) had H1N1 2009 (10.6 cases per million inhabitants; 95% confidence interval (CI), 9.4 to 11.9) which was an observed incidence of 33% of that in 2009 (P < 0.001). The maximum daily ICU occupancy was 2.4 beds (95% CI, 1.8 to 3) per million inhabitants in 2010 compared with 7.5 (95% CI, 6.5 to 8.6) in 2009, (P < 0.001). The onset of the epidemic in 2010 was delayed by five weeks compared with 2009. The clinical characteristics were similar in 2010 and 2009 with no difference in the age distribution, proportion of patients treated with mechanical ventilation, duration of ICU admission, or hospital mortality. Unlike 2009 the incidence of critical illness was significantly greater in New Zealand (18.8 cases per million inhabitants compared with 9 in Australia, P < 0.001). Of 170 patients with known vaccination status, 26 (15.3%) had been vaccinated against H1N1 2009. Conclusions During the 2010 ANZ winter, the impact of H1N1 2009 on ICU services was still appreciable in Australia and substantial in New Zealand. Vaccination failure occurred. PMID:21658233

  12. The influenza A (H1N1) pandemic in Reunion Island: knowledge, perceived risk and precautionary behaviour

    PubMed Central

    2013-01-01

    Background The effectiveness of preventive measures depends on prevailing attitudes and mindsets within a population. Perceived risk is central to a shift in mindset and behaviour. The present study aims to investigate the perceived severity, vulnerability and precautionary behaviour adopted in response to the influenza A (H1N1) epidemic that broke out in 2009 on Reunion Island (Indian Ocean). As no H1N1 vaccination was available at the time, non-medical interventions appeared of crucial importance to the control of the epidemic. Methods A cross sectional survey was conducted in Reunion Island between November 2009 and April 2010 within 2 months of the passage of the influenza A (H1N1) epidemic wave. Individual contacts representing 725 households (one contact per household) were interviewed by telephone using validated questionnaires on perceived risks. Mean scores were calculated for perceived severity, vulnerability, efficacy of preventive measures and precautionary behaviour. Univariate analysis was applied to identify preventive measures and attitudes and multivariate analysis was used to study the determinants of precautionary behaviour. Results More than 95% of contacted persons accepted to participate to the survey. Eighty seven percent of respondents believed that prevention was possible. On average, three out of six preventive measures were deemed effective. Spontaneously, 57% of the respondents reported that they took one or more preventive measures. This percentage increased to 87% after the interviewer detailed possible precautions one by one. The main precautions taken were frequent hand washing (59%) and avoidance of crowded places (34%). In multivariate logistic regression analysis the following factors were significantly associated with taking one or more preventive measures: young age, previous vaccination against seasonal influenza, having had seasonal influenza in the last five years, effectiveness of the preventive measures taken and low

  13. H1N1 infection in Pregnancy: clinical course in two women.

    PubMed

    Karabulut, Aysun; Calışkan, Alpaslan; Göncü, Ferzan; Uyar, Samet; Kutlu, Murat

    2011-01-01

    Pregnant women are one of the major risk groups for disease related morbidity and mortality from influenza A (H1N1, swine flu) pandemic. Healthy pregnant women are supposed to have 4 to 5 fold increased rate of serious illness and hospitalization compared to non-pregnant subjects. Herein, the clinical course of novel influenza A (H1N1) infection in two pregnant women was presented. One woman expired due to delay in treatment, while the other one was discharged on day six after prompt treatment. We would like to emphasize that obstetricians should be aware of the clinical and radiological manifestations of influenza A for prompt diagnosis and treatment. Obstetricians also should prepare themselves to provide adequate care for pregnancy related complications encountered by pregnant women with H1N1 infection.

  14. Social class based on occupation is associated with hospitalization for A(H1N1)pdm09 infection. Comparison between hospitalized and ambulatory cases.

    PubMed

    Pujol, J; Godoy, P; Soldevila, N; Castilla, J; González-Candelas, F; Mayoral, J M; Astray, J; Garcia, S; Martin, V; Tamames, S; Delgado, M; Domínguez, A

    2016-03-01

    This study aimed to analyse the existence of an association between social class (categorized by type of occupation) and the occurrence of A(H1N1)pmd09 infection and hospitalization for two seasons (2009-2010 and 2010-2011). This multicentre study compared ambulatory A(H1N1)pmd09 confirmed cases with ambulatory controls to measure risk of infection, and with hospitalized A(H1N1)pmd09 confirmed cases to asses hospitalization risk. Study variables were: age, marital status, tobacco and alcohol use, pregnancy, chronic obstructive pulmonary disease, chronic respiratory failure, cardiovascular disease, diabetes, chronic liver disease, body mass index >40, systemic corticosteroid treatment and influenza vaccination status. Occupation was registered literally and coded into manual and non-manual worker occupational social class groups. A conditional logistic regression analysis was performed. There were 720 hospitalized cases, 996 ambulatory cases and 1062 ambulatory controls included in the study. No relationship between occupational social class and A(H1N1)pmd09 infection was found [adjusted odds ratio (aOR) 0·97, 95% confidence interval (CI) 0·74-1·27], but an association (aOR 1·53, 95% CI 1·01-2·31) between occupational class and hospitalization for A(H1N1)pmd09 was observed. Influenza vaccination was a protective factor for A(H1N1)pmd09 infection (aOR 0·41, 95% CI 0·23-0·73) but not for hospitalization. We conclude that manual workers have the highest risk of hospitalization when infected by influenza than other occupations but they do not have a different probability of being infected by influenza.

  15. A Large Proportion of the Mexican Population Remained Susceptible to A(H1N1)pdm09 Infection One Year after the Emergence of 2009 Influenza Pandemic

    PubMed Central

    Veguilla, Vic; López-Gatell, Hugo; López-Martínez, Irma; Aparicio-Antonio, Rodrigo; Barrera-Badillo, Gisela; Rojo-Medina, Julieta; Gross, Felicia Liaini; Jefferson, Stacie N.; Katz, Jacqueline M.; Hernández-Ávila, Mauricio; Alpuche-Aranda, Celia M.

    2016-01-01

    Background The 2009 H1N1 influenza pandemic initially affected Mexico from April 2009 to July 2010. By August 2010, a fourth of the population had received the monovalent vaccine against the pandemic virus (A(H1N1)pdm09). To assess the proportion of the Mexican population who remained potentially susceptible to infection throughout the summer of 2010, we estimated the population seroprevalence to A(H1N1)pdm09 in a serosurvey of blood donors. Methods We evaluated baseline cross-reactivity to the pandemic strain and set the threshold for seropositivity using pre-pandemic (2005–2008) stored serum samples and sera from confirmed A(H1N1)pdm09 infected individuals. Between June and September 2010, a convenience sample serosurvey of adult blood donors, children, and adolescents was conducted in six states of Mexico. Sera were tested by the microneutralization (MN) and hemagglutination inhibition (HI) assays, and regarded seropositive if antibody titers were equal or exceeded 1:40 for MN and 1:20 for HI. Age-standardized seroprevalence were calculated using the 2010 National Census population. Results Sera from 1,484 individuals were analyzed; 1,363 (92%) were blood donors, and 121 (8%) children or adolescents aged ≤19 years. Mean age (standard deviation) was 31.4 (11.5) years, and 276 (19%) were women. A total of 516 (35%) participants declared history of influenza vaccination after April 2009. The age-standardized seroprevalence to A(H1N1)pdm09 was 48% by the MN and 41% by the HI assays, respectively. The youngest quintile, aged 1 to 22 years, had the highest the seroprevalence; 61% (95% confidence interval [CI]: 56, 66%) for MN, and 56% (95% CI: 51, 62%) for HI. Conclusions Despite high transmission of A(H1N1)pdm09 observed immediately after its emergence and extensive vaccination, over a half of the Mexican population remained potentially susceptible to A(H1N1)pdm09 infection. Subsequent influenza seasons with high transmission of A(H1N1)pdm09, as 2011–2012 and

  16. Diversifying Selection Analysis Predicts Antigenic Evolution of 2009 Pandemic H1N1 Influenza A Virus in Humans

    PubMed Central

    Lee, Alexandra J.; Das, Suman R.; Wang, Wei; Fitzgerald, Theresa; Pickett, Brett E.; Aevermann, Brian D.; Topham, David J.; Falsey, Ann R.

    2015-01-01

    ABSTRACT 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. IMPORTANCE 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

  17. Precipitation of new onset diabetes by H1N1 infection.

    PubMed

    Krishna, S V S; Sunil, K; Prasad, R Devi; Modi, K D

    2012-12-01

    Infectious diseases in type 2 diabetes can complicate diabetic ketoacidosis, derange hyperglycemia, or precipitate new onset diabetes. Pulmonary tuberculosis being the most common. High index of clinical suspicion is required for co-existing H1N1 virus, which if present has high mortality if not treated. A 63-year-old female, with no known chronic illness, was hospitalized in month of Aug 2010 with influenza-like symptoms and diabetes. Quick evaluation revealed tachycardia, tachypnea, p02 90% at room air, and normotensive. Clinical chest examination was normal. Further evaluation revealed NHO in both lung fields on chest X-ray, hyperglycemia 325 mg/dl, detected for first time. Her signs and symptoms were out of proportion to clinical findings and chest X-ray findings. Patient was managed with insulin infusion and empirical broad-spectrum antibiotic coverage in ICU. As her condition worsened over next 12 hrs, infection with H1N1 was suspected and empirically started on oseltamavir after taking throat swab for H1N1 test and later, the sample was tested positive for H1N1 influenza by RT-PCR. Clinical course in the hospital was complicated by oxygen dependence requiring 10-12 ltr/hr by nasal mask. She made an uneventful recovery. In a known diabetic, infection with H1N1 quadruples ICU hospitalization, and only few cases of new onset diabetes with H1N1 were reported. Two reported from Iran had fatal outcome. This case emphasis on clinical acumen in recognition, and prompt institution of therapy will reduce associated mortality.

  18. Influenza A/H1N1 Severe Pneumonia: Novel Morphocytological Findings in Bronchoalveolar Lavage

    PubMed Central

    Faverio, Paola; Messinesi, Grazia; Brenna, Ambrogio; Pesci, Alberto

    2014-01-01

    We present the results of bronchoalveolar lavage (BAL) performed in three patients with severe influenza A/H1N1 pneumonia complicated by acute respiratory distress syndrome (ARDS). Light microscopy analysis of BAL cytocentrifugates showed the presence of characteristic large, mononuclear, plasmoblastic/plasmocytoid-like cells never described before. Via transmission electron microscopy, these cells were classified as atypical type II pneumocytes and some of them showed cytoplasmic vesicles and inclusions. We concluded that plasmoblastic/plasmocytoid-like type II pneumocytes might represent a morphologic marker of A/H1N1 influenza virus infection as well as reparative cellular activation after diffuse alveolar damage. PMID:25383078

  19. Influenza A/H1N1 Severe Pneumonia: Novel Morphocytological Findings in Bronchoalveolar Lavage.

    PubMed

    Faverio, Paola; Aliberti, Stefano; Ezekiel, Clinton; Messinesi, Grazia; Brenna, Ambrogio; Pesci, Alberto

    2014-01-01

    We present the results of bronchoalveolar lavage (BAL) performed in three patients with severe influenza A/H1N1 pneumonia complicated by acute respiratory distress syndrome (ARDS). Light microscopy analysis of BAL cytocentrifugates showed the presence of characteristic large, mononuclear, plasmoblastic/plasmocytoid-like cells never described before. Via transmission electron microscopy, these cells were classified as atypical type II pneumocytes and some of them showed cytoplasmic vesicles and inclusions. We concluded that plasmoblastic/plasmocytoid-like type II pneumocytes might represent a morphologic marker of A/H1N1 influenza virus infection as well as reparative cellular activation after diffuse alveolar damage.

  20. Amino acids transitioning of 2009 H1N1pdm in Taiwan from 2009 to 2011.

    PubMed

    Chen, Guang-Wu; Tsao, Kuo-Chien; Huang, Chung-Guei; Gong, Yu-Nong; Chang, Shih-Cheng; Liu, Yi-Chun; Wu, Hsiao-Han; Yang, Shu-Li; Lin, Tzou-Yien; Huang, Yhu-Chering; Shih, Shin-Ru

    2012-01-01

    A swine-origin influenza A was detected in April 2009 and soon became the 2009 H1N1 pandemic strain (H1N1pdm). The current study revealed the genetic diversity of H1N1pdm, based on 77 and 70 isolates which we collected, respectively, during the 2009/2010 and 2010/2011 influenza seasons in Taiwan. We focused on tracking the amino acid transitioning of hemagglutinin (HA) and neuraminidase (NA) genes in the early diversification of the virus and compared them with H1N1pdm strains reported worldwide. We identified newly emerged mutation markers based on A/California/04/2009, described how these markers shifted from the first H1N1pdm season to the one that immediately followed, and discussed how these observations may relate to antigenicity, receptor-binding, and drug susceptibility. It was found that the amino acid mutation rates of H1N1pdm were elevated, from 9.29×10(-3) substitutions per site in the first season to 1.46×10(-2) in the second season in HA, and from 5.23×10(-3) to 1.10×10(-2) in NA. Many mutation markers were newly detected in the second season, including 11 in HA and 8 in NA, and some were found having statistical correlation to disease severity. There were five noticeable HA mutations made to antigenic sites. No significant titer changes, however, were detected based on hemagglutination inhibition tests. Only one isolate with H275Y mutation known to reduce susceptibility to NA inhibitors was detected. As limited Taiwanese H1N1pdm viruses were isolated after our sampling period, we gathered 8,876 HA and 6,017 NA H1N1pdm sequences up to April 2012 from NCBI to follow up the dynamics of mentioned HA mutations. While some mutations described in this study seemed to either settle in or die out in the 2011-2012 season, a number of them still showed signs of transitioning, prompting the importance of continuous monitoring of this virus for more seasons to come.

  1. Cross-reactive T cells are involved in rapid clearance of 2009 pandemic H1N1 influenza virus in nonhuman primates.

    PubMed

    Weinfurter, Jason T; Brunner, Kevin; Capuano, Saverio V; Li, Chengjun; Broman, Karl W; Kawaoka, Yoshihiro; Friedrich, Thomas C

    2011-11-01

    In mouse models of influenza, T cells can confer broad protection against multiple viral subtypes when antibodies raised against a single subtype fail to do so. However, the role of T cells in protecting humans against influenza remains unclear. Here we employ a translational nonhuman primate model to show that cross-reactive T cell responses play an important role in early clearance of infection with 2009 pandemic H1N1 influenza virus (H1N1pdm). To "prime" cellular immunity, we first infected 5 rhesus macaques with a seasonal human H1N1 isolate. These animals made detectable cellular and antibody responses against the seasonal H1N1 isolate but had no neutralizing antibodies against H1N1pdm. Four months later, we challenged the 5 "primed" animals and 7 naive controls with H1N1pdm. In naive animals, CD8+ T cells with an activated phenotype (Ki-67+ CD38+) appeared in blood and lung 5-7 days post inoculation (p.i.) with H1N1pdm and reached peak magnitude 7-10 days p.i. In contrast, activated T cells were recruited to the lung as early as 2 days p.i. in "primed" animals, and reached peak frequencies in blood and lung 4-7 days p.i. Interferon (IFN)-γ Elispot and intracellular cytokine staining assays showed that the virus-specific response peaked earlier and reached a higher magnitude in "primed" animals than in naive animals. This response involved both CD4+ and CD8+ T cells. Strikingly, "primed" animals cleared H1N1pdm infection significantly earlier from the upper and lower respiratory tract than the naive animals did, and before the appearance of H1N1pdm-specific neutralizing antibodies. Together, our results suggest that cross-reactive T cell responses can mediate early clearance of an antigenically novel influenza virus in primates. Vaccines capable of inducing such cross-reactive T cells may help protect humans against severe disease caused by newly emerging pandemic influenza viruses.

  2. The 2009 pandemic H1N1 and triple-reassortant swine H1N1 influenza viruses replicate efficiently but elicit an attenuated inflammatory response in polarized human bronchial epithelial cells.

    PubMed

    Zeng, Hui; Pappas, Claudia; Katz, Jacqueline M; Tumpey, Terrence M

    2011-01-01

    The pandemic H1N1 virus of 2009 (2009 H1N1) produced a spectrum of disease ranging from mild illness to severe illness and death. Respiratory symptoms were frequently associated with virus infection, with relatively high rate of gastrointestinal symptoms reported. To better understand 2009 H1N1 virus pathogenesis in humans, we studied virus and host responses following infection of two cell types: polarized bronchial and pharyngeal epithelial cells, which exhibit many features of the human airway epithelium, and colon epithelial cells to serve as a human intestinal cell model. Selected 2009 H1N1 viruses were compared to both seasonal H1N1 and triple-reassortant swine H1N1 influenza viruses that have circulated among North American pigs since before the 2009 pandemic. All H1N1 viruses replicated productively in airway cells; however, in contrast to seasonal H1N1 virus infection, infection with the 2009 H1N1 and triple-reassortant swine H1N1 viruses resulted in an attenuated inflammatory response, a weaker interferon response, and reduced cell death. Additionally, the H1N1 viruses of swine origin replicated less efficiently at the temperature of the human proximal airways (33°C). We also observed that the 2009 H1N1 viruses replicated to significantly higher titers than seasonal H1N1 virus in polarized colon epithelial cells. These studies reveal that in comparison to seasonal influenza virus, H1N1 viruses of swine origin poorly activate multiple aspects of the human innate response, which may contribute to the virulence of these viruses. In addition, their less efficient replication at human upper airway temperatures has implications for the understanding of pandemic H1N1 virus adaptation to humans.

  3. In Silico Functional and Structural Characterization of H1N1 Influenza A Viruses Hemagglutinin, 2010-2013, Shiraz, Iran.

    PubMed

    Moattari, Afagh; Dehghani, Behzad; Khodadad, Nastaran; Tavakoli, Forogh

    2015-06-01

    Hemagglutinin (HA) is a major virulence factor of influenza viruses and plays an important role in viral pathogenesis. Analysis of amino acid changes, epitopes' regions, glycosylation and phosphorylation sites have greatly contributed to the development of new generations of vaccine. The hemagglutinins of 10 selected isolates, 8 of 2010 and 2 of 2013 samples were sequenced and analyzed by several bioinformatic softwares and the results were compared with those of 3 vaccine isolates. The study detected several amino acid changes related to altered epitopes' sites, modification sites and physico-chemical properties. The results showed some conserved modification sites in HA structure. This study is the first analytical research on isolates obtained from Shiraz, Iran, and our results can be used to better understand the genetic diversity and antigenic variations in Iranian and Asian H1N1 pathogenic strains.

  4. Full-Genome Sequence of a Reassortant H1N1 Swine Influenza Virus Isolated from Pigs in Italy.

    PubMed

    Chiapponi, Chiara; Baioni, Laura; Luppi, Andrea; Moreno, Ana; Castellan, Alberto; Foni, Emanuela

    2013-10-03

    In this study, the full-genome sequence of a novel reassortant H1N1 swine influenza virus (SIV) is reported. The isolate has a hemagglutinin (HA) gene of the pandemic H1N1 influenza virus, but it carries the seven genome segments of the avian-origin H1N1 SIV currently circulating in European pig farms.

  5. Full-Genome Sequence of a Reassortant H1N1 Swine Influenza Virus Isolated from Pigs in Italy

    PubMed Central

    Chiapponi, Chiara; Baioni, Laura; Luppi, Andrea; Moreno, Ana; Castellan, Alberto

    2013-01-01

    In this study, the full-genome sequence of a novel reassortant H1N1 swine influenza virus (SIV) is reported. The isolate has a hemagglutinin (HA) gene of the pandemic H1N1 influenza virus, but it carries the seven genome segments of the avian-origin H1N1 SIV currently circulating in European pig farms. PMID:24092781

  6. Comparative virulence of wild-type H1N1pdm09 influenza A isolates in swine

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In 2009, a novel swine-origin H1N1 (H1N1pdm09) influenza A virus (IAV) reached pandemic status and was soon after detected in pigs worldwide. The objective of this study was to evaluate whether differences in the HA protein can affect pathogenicity and antigenicity of H1N1pdm09 in swine. We compared...

  7. WHO recommendations for the viruses used in the 2013-2014 Northern Hemisphere influenza vaccine: Epidemiology, antigenic and genetic characteristics of influenza A(H1N1)pdm09, A(H3N2) and B influenza viruses collected from October 2012 to January 2013.

    PubMed

    Barr, Ian G; Russell, Colin; Besselaar, Terry G; Cox, Nancy J; Daniels, Rod S; Donis, Ruben; Engelhardt, Othmar G; Grohmann, Gary; Itamura, Shigeyuki; Kelso, Anne; McCauley, John; Odagiri, Takato; Schultz-Cherry, Stacey; Shu, Yuelong; Smith, Derek; Tashiro, Masato; Wang, Dayan; Webby, Richard; Xu, Xiyan; Ye, Zhiping; Zhang, Wenqing

    2014-08-20

    In February the World Health Organisation (WHO) recommends influenza viruses to be included in influenza vaccines for the forthcoming winter in the Northern Hemisphere. These recommendations are based on data collected by National Influenza Centres (NICs) through the WHO Global Influenza Surveillance and Response System (GISRS) and a more detailed analysis of representative and potential antigenically variant influenza viruses from the WHO Collaborating Centres for Influenza (WHO CCs) and Essential Regulatory Laboratories (ERLs). This article provides a detailed summary of the antigenic and genetic properties of viruses and additional background data used by WHO experts during development of the recommendations of the 2013-2014 Northern Hemisphere influenza vaccine composition.

  8. The hemagglutinin structure of an avian H1N1 influenza A virus

    SciTech Connect

    Lin, Tianwei; Wang, Gengyan; Li, Anzhang; Zhang, Qian; Wu, Caiming; Zhang, Rongfu; Cai, Qixu; Song, Wenjun; Yuen, Kwok-Yung

    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/receptor 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.

  9. Zoonoses: USDA ARS Lessons Learned During Novel Influenza H1N1 Investigations

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Influenza illness was first recognized in pigs during the 1918 human Spanish flu pandemic, and influenza A virus has since remained of importance to the swine industry as a primary respiratory pathogen. Influenza virus H1N1 remained relatively stable in U.S. swine for nearly 80 years following 1918...

  10. Pandemic H1N1 influenza virus infection in a Canadian cat

    PubMed Central

    Knight, Cameron G.; Davies, Jennifer L.; Joseph, Tomy; Ondrich, Sarah; Rosa, Brielle V.

    2016-01-01

    A cat was presented for necropsy after being found dead at home. Histologic findings suggested viral pneumonia. Polymerase chain reaction and viral typing revealed influenza A(H1N1)pdm09. This is the first report of influenza in a Canadian cat and highlights the importance of considering influenza virus in the differential diagnosis for feline respiratory distress. PMID:27152036

  11. H1N1 Preventive Health Behaviors in a University Setting

    PubMed Central

    Katz, Rebecca; May, Larissa; Sanza, Megan; Johnston, Lindsay; Petinaux, Bruno

    2011-01-01

    Abstract Background: When H1N1 emerged in 2009, institutions of higher education were immediately faced with questions about how best to protect their community from the virus, yet limited information existed to help predict student preventive behaviors. Methods: The authors surveyed students at a large urban university in November 2009 to better understand how students perceived their susceptibility to and the severity of H1N1, which preventive behaviors they engaged in, and if policies impacted their preventive health decisions. Results: Preventive health behavior messaging had a mixed impact on students. Students made simple behavior changes to protect themselves from H1N1, especially if they perceived a high personal risk of contracting H1N1. Although policies were instituted to enable students to avoid classes when ill, almost no student self-isolated for the entire duration of their illness. Conclusions: These findings can help inform future decision making in a university setting to best influence preventive health behaviors. PMID:22171729

  12. Influenza virus A (H1N1) in giant anteaters (Myrmecophaga tridactyla).

    PubMed

    Nofs, Sally; Abd-Eldaim, Mohamed; Thomas, Kathy V; Toplon, David; Rouse, Dawn; Kennedy, Melissa

    2009-07-01

    In February 2007, an outbreak of respiratory disease occurred in a group of giant anteaters (Myrmecophaga tridactyla) at the Nashville Zoo. Isolates from 2 affected animals were identified in March 2007 as a type A influenza virus related to human influenza subtype H1N1.

  13. Evolutionary complexities of swine flu H1N1 gene sequences of 2009.

    PubMed

    Sinha, Niladri Kumar; Roy, Ayan; Das, Ballari; Das, Santasabuj; Basak, Surajit

    2009-12-18

    A recently emerged novel influenza A (H1N1) virus continues to spread globally. The pandemic caused by this new H1N1 swine influenza virus presents an opportunity to analyze the evolutionary significance of the origin of the new strain of swine flu. Our study clearly suggests that strong purifying selection is responsible for the evolution of the novel influenza A (H1N1) virus among human. We observed that the 2009 viral sequences are evolutionarily widely different from the past few years' sequences. Rather, the 2009 sequences are evolutionarily more similar to the most ancient sequence reported in the NCBI Influenza Virus Resource Database collected in 1918. Analysis of evolutionary rates also supports the view that all the genes in the pandemic strain of 2009 except NA and M genes are derived from triple reassorted swine viruses. Our study demonstrates the importance of using complete-genome approach as more sequences will become available to investigate the evolutionary origin of the 1918 influenza A (H1N1) swine flu strain and the possibility of future reassortment events.

  14. Pandemic (H1N1) 2009 outbreak at camp for children with hematologic and oncologic conditions.

    PubMed

    Morrison, Cori; Maurtua-Neumann, Paola; Myint, Myo Thwin; Drury, Stacy S; Bégué, Rodolfo E

    2011-01-01

    An outbreak of influenza A pandemic (H1N1) 2009 occurred among campers and staff at a summer camp attended by children with hematologic and oncologic conditions. The overall attack rate was 36% and was highest among children and adolescents (43%), persons with cancer (48%), and persons with sickle cell disease (82%).

  15. Influenza A(H1N1)pdm09 Virus Infection in Giant Pandas, China

    PubMed Central

    Li, Desheng; Zhu, Ling; Cui, Hengmin; Ling, Shanshan; Fan, Shengtao; Yu, Zhijun; Zhou, Yuancheng; Wang, Tiecheng; Qian, Jun; Xia, Xianzhu; Xu, Zhiwen; Wang, Chengdong

    2014-01-01

    We confirmed infection with influenza A(H1N1)pdm09 in giant pandas in China during 2009 by using virus isolation and serologic analysis methods. This finding extends the host range of influenza viruses and indicates a need for increased surveillance for and control of influenza viruses among giant pandas. PMID:24565026

  16. Rural Responses to H1N1: A Flexible Model for Community Collaboration

    ERIC Educational Resources Information Center

    O'Farrell, Denise; Aubrey, Debra Larsen

    2010-01-01

    This paper examines a regional 2009 H1N1 rural response model, which utilises community partnerships with local government, county emergency management, public health, private healthcare, Medical Reserve Corps volunteers, and other organisations in rural Southeast Idaho. Unique aspects of the collaborative use of federal, state, county, and…

  17. Phylogenetic evolution of swine-origin human influenza virus: a pandemic H1N1 2009.

    PubMed

    Kowalczyk, A; Markowska-Daniel, I

    2010-01-01

    The knowledge of the genome constellation in pandemic influenza A virus H1N1 2009 from different countries and different hosts is valuable for monitoring and understanding of the evolution and migration of these strains. The complete genome sequences of selected worldwide distributed influenza A viruses are publicly available and there have been few longitudinal genome studies of human, avian and swine influenza A viruses. All possible to download SIV sequences of influenza A viruses available at GISAID Platform (Global Initiative on Sharing Avian Influenza Data) were analyzed firstly through the web servers of the Influenza Virus Resource in NCBI. Phylogenetic study of circulating human pandemic H1N1 virus indicated that the new variant possesses a distinctive evolutionary trait. There is no one way the pandemic H1N1 have acquired new genes from other distinguishable viruses circulating recently in local human, pig or domestic poultry populations from various geographic regions. The extensive genetic diversity among whole segments present in pandemic H1N1 genome suggests that multiple introduction of virus have taken place during the period 1999-2009. The initial interspecies transmission could have occurred in the long-range past and after it the reassortants steps lead to three lineages: classical SIV prevalent in the North America, avian-like SIV in Europe and avian-like related SIV in Asia. This analysis contributes to the evidence that pigs are not the only hosts playing the role of "mixing vessel", as it was suggested for many years.

  18. H1N1 Flu (Swine Flu) - Multiple Languages: MedlinePlus

    MedlinePlus

    ... to Protect Your Child and Family from the Flu this School Year English 本学年家长预防子女和家人感染流感应采取的措施 - 简体中文 (Chinese - Simplified) PDF Centers for Disease Control and Prevention Spanish (español) Gripe H1N1 (gripe porcina) Characters not displaying ...

  19. Information Entropy Analysis of the H1N1 Genetic Code

    NASA Astrophysics Data System (ADS)

    Martwick, Andy

    2010-03-01

    During the current H1N1 pandemic, viral samples are being obtained from large numbers of infected people world-wide and are being sequenced on the NCBI Influenza Virus Resource Database. The information entropy of the sequences was computed from the probability of occurrence of each nucleotide base at every position of each set of sequences using Shannon's definition of information entropy, [ H=∑bpb,2( 1pb ) ] where H is the observed information entropy at each nucleotide position and pb is the probability of the base pair of the nucleotides A, C, G, U. Information entropy of the current H1N1 pandemic is compared to reference human and swine H1N1 entropy. As expected, the current H1N1 entropy is in a low entropy state and has a very large mutation potential. Using the entropy method in mature genes we can identify low entropy regions of nucleotides that generally correlate to critical protein function.

  20. Experimental Challenge with Two Isolates of 2009 A/H1N1 in Weaned Pigs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Introduction. The gene constellation of the 2009 pandemic H1N1 virus is a unique combination from swine influenza A viruses (SIV) of North American and Eurasian lineages, but prior to April 2009 had never before been identified in swine or other species (1). Although the hemagglutinin gene is relate...

  1. Research Updates: Experimental Evaluation of 2009 Pandemic A/H1N1 in Pigs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Introduction: In March 2009, a novel pandemic A/H1N1 emerged in the human population in North America (2). The gene constellation of the emerging virus was demonstrated to be a combination of genes from swine influenza A viruses (SIV) of North American and Eurasian lineages that had never before be...

  2. Enhanced Pneumonia With Pandemic 2009 A/H1N1 Swine Influenza Virus in Pigs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Introduction. Swine influenza A viruses (SIV) in the major swine producing regions of North America consist of multiple subtypes of endemic H1N1, H1N2, and H3N2 derived from swine, avian and human influenza viruses with a triple reassortant internal gene (TRIG) constellation (1). Genetic drift and r...

  3. Influenza A(H1N1)pdm09 virus infection in giant pandas, China.

    PubMed

    Li, Desheng; Zhu, Ling; Cui, Hengmin; Ling, Shanshan; Fan, Shengtao; Yu, Zhijun; Zhou, Yuancheng; Wang, Tiecheng; Qian, Jun; Xia, Xianzhu; Xu, Zhiwen; Gao, Yuwei; Wang, Chengdong

    2014-03-01

    We confirmed infection with influenza A(H1N1)pdm09 in giant pandas in China during 2009 by using virus isolation and serologic analysis methods. This finding extends the host range of influenza viruses and indicates a need for increased surveillance for and control of influenza viruses among giant pandas.

  4. Travel and age of influenza A (H1N1) 2009 virus infection.

    PubMed

    Nishiura, Hiroshi

    2010-01-01

    Age distribution of 4,986 cases of influenza A (H1N1) 2009 in Japan was analyzed. Cases with a travel history within 10 days preceding the illness onset were significantly older than indigenous cases (p < 0.01) reflecting age-specific travel patterns. Border controls should account for the high frequency of infection among adults.

  5. Increased virulence of neuraminidase inhibitor-resistant pandemic H1N1 virus in mice

    PubMed Central

    Song, Min-Suk; Hee Baek, Yun; Kim, Eun-Ha; Park, Su-Jin; Kim, Semi; Lim, Gyo-Jin; Kwon, Hyeok-il; Pascua, Philippe Noriel Q; Decano, Arun G; Lee, Byeong-Jae; Kim, Young-Il; Webby, Richard J; Choi, Young-Ki

    2013-01-01

    Pandemic H1N1 2009 (A[H1N1]pdm09) variants associated with oseltamivir resistance have emerged with a histidine-to-tyrosine substitution in the neuraminidase(NA) at position 274 (H274Y). To determine whether the H274Y variant has increased virulence potential, A(H1N1)pdm09 virus, with or without the H274Y mutation, was adapted by serial lung-to-lung passages in mice. The mouse-adapted H274Y (maCA04H274Y) variants showed increased growth properties and virulence in vitro and in vivo while maintaining high NA inhibitor resistance. Interestingly, most maCA04H274Y and maCA04 viruses acquired common mutations in HA (S183P and D222G) and NP (D101G), while only maCA04H274Y viruses had consensus additional K153E mutation in the HA gene, suggesting a potential association with the H274Y substitution. Collectively, our findings highlight the potential emergence of A(H1N1)pdm09 drug-resistant variants with increased virulence and the need for rapid development of novel antiviral drugs. PMID:23924955

  6. The resurgence of swine-origin influenza A (H1N1).

    PubMed

    Mossad, Sherif Beniameen

    2009-06-01

    Unexpectedly, swine-origin influenza A (H1N1) virus (S-OIV, informally known as swine flu) appeared in North America at the very end of the 2008-2009 influenza season and began to spread internationally. As the world mobilizes for a potential pandemic, this article summarizes the developments in diagnosis, treatment, and prevention.

  7. Antigenic and genetic analyses of H1N1 influenza A viruses from European pigs.

    PubMed

    Brown, I H; Ludwig, S; Olsen, C W; Hannoun, C; Scholtissek, C; Hinshaw, V S; Harris, P A; McCauley, J W; Strong, I; Alexander, D J

    1997-03-01

    H1N1 influenza A viruses isolated from pigs in Europe since 1981 were examined both antigenically and genetically and compared with H1N1 viruses from other sources. H1N1 viruses from pigs and birds could be divided into three groups: avian, classical swine and 'avian-like' swine viruses. Low or no reactivity of 'avian-like' swine viruses in HI tests with monoclonal antibodies raised against classical swine viruses was associated with amino acid substitutions within antigenic sites of the haemagglutinin (HA). Phylogenetic analysis of the HA gene revealed that classical swine viruses from European pigs are most similar to each other and are closely related to North American swine strains, whilst the 'avian-like' swine viruses cluster with avian viruses. 'Avian-like' viruses introduced into pigs in the UK in 1992 apparently originated directly from strains in pigs in continental Europe at that time. The HA genes of the swine viruses examined had undergone limited variation in antigenic sites and also contained fewer potential glycosylation sites compared to human H1N1 viruses. The HA exhibited antigenic drift which was more marked in 'avian-like' swine viruses than in classical swine strains. Genetic analyses of two recent 'avian-like' swine viruses indicated that all the RNA segments are related most closely to those of avian influenza A viruses.

  8. Predicting psychological responses to influenza A, H1N1 ("swine flu"): the role of illness perceptions.

    PubMed

    Williams, Lynn; Regagliolo, Anna; Rasmussen, Susan

    2012-01-01

    Previous research on H1N1 ("Swine flu") has demonstrated that although the public reported concern about H1N1, knowledge levels were low, as were reports of behavioural changes aimed at minimising the spread of H1N1. The current study had two main aims; (i) to ascertain levels of state anxiety and knowledge about H1N1, and (ii) to examine if illness perceptions predict anxiety about H1N1, perceived risk of contracting H1N1, and knowledge about H1N1. The study was cross-sectional in design, and involved 235 participants (100 males, 135 females, mean age 22.48 years) completing self-report measures of knowledge, anxiety, and perceived risk about H1N1, and illness perceptions (BIPQ). Analyses revealed low levels of knowledge about H1N1, 37.4% of participants could not identify any of the causes of H1N1. Correlation and multiple regression analyses demonstrated that illness perceptions were associated with responses to H1N1, with negative illness perceptions predicting state anxiety (β = 0.498, p < 0.01) and perceived risk of contracting H1N1 (β = 0.346, p < 0.01). In addition, females (M = 10.07, SD = 2.68) were found to have higher levels of knowledge about H1N1, compared to males (M = 8.29, SD = 2.65), t(233) = -5.08, p < 0.001. These findings suggest low levels of knowledge about the causes, symptoms and possible preventive measures associated with H1N1. In addition, the current study points to a key role for illness perceptions in predicting psychological responses to H1N1.

  9. The prevalance of respiratory viruses among healthcare workers serving pilgrims in Makkah during the 2009 influenza A (H1N1) pandemic.

    PubMed

    Memish, Ziad A; Assiri, Abdullah M; Alshehri, Mohammed; Hussain, Raheela; Alomar, Ibrahim

    2012-01-01

    Despite the high risk of acquiring respiratory infections, healthcare workers who treat pilgrims at Hajj have not been studied in previous research on respiratory diseases during Hajj. The objective of this study was to determine the prevalence of different respiratory viruses among healthcare workers who treated pilgrims during Hajj 2009, the year of the influenza A H1N1 pandemic. A cross-sectional study was performed just before and after Hajj (25-29 November, 2009). Nasal and throat swabs were tested for 18 respiratory virus types and subtypes. A total of 184 healthcare workers were examined. Most were men (85%) with an average age of 41 years. Before the Hajj, rates of seasonal influenza vaccination were higher (51%) than rates of pandemic influenza A H1N1 vaccination (22%). After the Hajj, participants reported high rates of maintaining hand hygiene (98%), cough etiquette (89%), and wearing a face mask (90%). Among all the viruses tested, only two were detected: rhinovirus was detected in 12.6% and Coronavirus 229E in 0.6%. Rhinovirus was detected in 21% of those who had respiratory symptoms during Hajj. Influenza A (including H1N1), influenza B. respiratory syncytial virus, other coronaviruses, parainfluenza viruses, human metapneumovirus, adenovirus, and human bocavirus were not detected. The finding of high rates of rhinovirus infection corresponds to their frequent occurrence in adults. None of the participants had influenza A H1N1 2009, possibly because it was also infrequent among the 2009 pilgrims.

  10. Prevalence of Seropositivity to Pandemic Influenza A/H1N1 Virus in the United States following the 2009 Pandemic

    PubMed Central

    Reed, Carrie; Katz, Jacqueline M.; Hancock, Kathy; Balish, Amanda; Fry, Alicia M.

    2012-01-01

    Background 2009 pandemic influenza A/H1N1 (A(H1N1)pdm09) was first detected in the United States in April 2009 and resulted in a global pandemic. We conducted a serologic survey to estimate the cumulative incidence of A(H1N1)pdm09 through the end of 2009 when pandemic activity had waned in the United States. Methods We conducted a pair of cross sectional serologic surveys before and after the spring/fall waves of the pandemic for evidence of seropositivity (titer ≥40) using the hemagglutination inhibition (HI) assay. We tested a baseline sample of 1,142 serum specimens from the 2007–2008 National Health and Nutrition Examination Survey (NHANES), and 2,759 serum specimens submitted for routine screening to clinical diagnostic laboratories from ten representative sites. Results The age-adjusted prevalence of seropositivity to A(H1N1)pdm09 by year-end 2009 was 36.9% (95%CI: 31.7–42.2%). After adjusting for baseline cross-reactive antibody, pandemic vaccination coverage and the sensitivity/specificity of the HI assay, we estimate that 20.2% (95%CI: 10.1–28.3%) of the population was infected with A(H1N1)pdm09 by December 2009, including 53.3% (95%CI: 39.0–67.1%) of children aged 5–17 years. Conclusions By December 2009, approximately one-fifth of the US population, or 61.9 million persons, may have been infected with A(H1N1)pdm09, including around half of school-aged children. PMID:23118949

  11. CD4+ T cell autoimmunity to hypocretin/orexin and cross-reactivity to a 2009 H1N1 influenza A epitope in narcolepsy.

    PubMed

    De la Herrán-Arita, Alberto K; Kornum, Birgitte Rahbek; Mahlios, Josh; Jiang, Wei; Lin, Ling; Hou, Tieying; Macaubas, Claudia; Einen, Mali; Plazzi, Giuseppe; Crowe, Catherine; Newell, Evan W; Davis, Mark M; Mellins, Elizabeth D; Mignot, Emmanuel

    2013-12-18

    Narcolepsy, a disorder strongly associated with human leukocyte antigen (HLA)-DQA1*01:02/DQB1*06:02 (DQ0602), is characterized by excessive daytime sleepiness, cataplexy, and rapid eye movement sleep abnormalities. It is caused by the loss of ~70,000 posterior hypothalamic neurons that produce the wake-promoting neuropeptide hypocretin (HCRT) (orexin). We identified two DQ0602-binding HCRT epitopes, HCRT56-68 and HCRT87-99, that activated a subpopulation of CD4(+) T cells in narcolepsy patients but not in DQ0602-positive healthy control subjects. Because of the established association of narcolepsy with the 2009 H1N1 influenza A strain (pH1N1), we administered a seasonal influenza vaccine (containing pH1N1) to patients with narcolepsy and found an increased frequency of circulating HCRT56-68- and HCRT87-99-reactive T cells. We also identified a hemagglutinin (HA) pHA1 epitope specific to the 2009 H1N1 strain, pHA1275-287, with homology to HCRT56-68 and HCRT87-99. In vitro stimulation of narcolepsy CD4(+) T cells with pH1N1 proteins or pHA1275-287 increased the frequency of HCRT56-68- and HCRT87-99-reactive T cells. Our data indicate the presence of CD4(+) T cells that are reactive to HCRT in narcolepsy patients and possible molecular mimicry between HCRT and a similar epitope in influenza pH1N1, pHA1275-287.

  12. Transmission of Pandemic Influenza A (H1N1) Virus in a Train in China

    PubMed Central

    Cui, Fuqiang; Luo, Huiming; Zhou, Lei; Yin, Dapeng; Zheng, Canjun; Wang, Dingming; Gong, Jian; Fang, Gang; He, Jianfeng; McFarland, Jeffrey; Yu, Hongjie

    2011-01-01

    Background Pandemic influenza A (H1N1) virus emerged in North America in April 2009 and spread globally. We describe the epidemiology and public health response to the first known outbreak of 2009 H1N1 in a train, which occurred in June 2009 in China. Methods After 2 provinces provided initial reports of 2009 H1N1 infection in 2 persons who had travelled on the same train, we conducted a retrospective epidemiologic investigation to collect information from the passengers, crew members, contacts, and health care providers. We explored the source of infection and possible routes of transmission in the train. All cases were confirmed by real-time reverse transcription polymerase chain reaction testing. Results Train #1223 traveled 40 hours, made 28 stops in 4 Chinese provinces, and boarded 2555 passengers, who logged a total of 59 144 person-hours of travel time. Nineteen confirmed 2009 H1N1 cases were identified. Of these, 13 were infected and developed symptoms on the train and 6 occurred among contacts who developed illness during medical monitoring. In addition, 3 asymptomatic cases were identified based on RT-PCR testing of respiratory swabs from contacts. The attack rate among contacts of confirmed cases in the same car was higher than that among contacts in other cars (3.15% vs. 0%, P < 0.001). Attack rates increased with exposure time. Conclusions Close contact and long exposure may have contributed to the transmission of 2009 H1N1 virus in the train. Trains may have played an important role in the 2009 influenza pandemic. PMID:21646746

  13. Inside the Outbreak of the 2009 Influenza A (H1N1)v Virus in Mexico

    PubMed Central

    Zepeda-Lopez, Hector M.; Perea-Araujo, Lizbeth; Miliar-García, Angel; Dominguez-López, Aarón; Xoconostle-Cázarez, Beatriz; Lara-Padilla, Eleazar; Ramírez Hernandez, Jorge A.; Sevilla-Reyes, Edgar; Orozco, Maria Esther; Ahued-Ortega, Armando; Villaseñor-Ruiz, Ignacio; Garcia-Cavazos, Ricardo J.; Teran, Luis M.

    2010-01-01

    Background Influenza viruses pose a threat to human health because of their potential to cause global disease. Between mid March and mid April a pandemic influenza A virus emerged in Mexico. This report details 202 cases of infection of humans with the 2009 influenza A virus (H1N1)v which occurred in Mexico City as well as the spread of the virus throughout the entire country. Methodology and Findings From May 1st to May 5th nasopharyngeal swabs, derived from 751 patients, were collected at 220 outpatient clinics and 28 hospitals distributed throughout Mexico City. Analysis of samples using real time RT-PCR revealed that 202 patients out of the 751 subjects (26.9%) were confirmed to be infected with the new virus. All confirmed cases of human infection with the strain influenza (H1N1)v suffered respiratory symptoms. The greatest number of confirmed cases during the outbreak of the 2009 influenza A (H1N1)v were seen in neighbourhoods on the northeast side of Mexico City including Iztapalapa, Gustavo A. Madero, Iztacalco, and Tlahuac which are the most populated areas in Mexico City. Using these data, together with data reported by the Mexican Secretariat of Health (MSH) to date, we plot the course of influenza (H1N1)v activity throughout Mexico. Conclusions Our data, which is backed up by MSH data, show that the greatest numbers of the 2009 influenza A (H1N1) cases were seen in the most populated areas. We speculate on conditions in Mexico which may have sparked this flu pandemic, the first in 41 years. We accept the hypothesis that high population density and a mass gathering which took in Iztapalapa contributed to the rapid spread of the disease which developed in three peaks of activity throughout the Country. PMID:20949040

  14. Influenza A(H1N1)pdm09 and postpandemic influenza in Lithuania

    PubMed Central

    Ambrozaitis, Arvydas; Radzišauskienė, Daiva; Kuprevičienė, Nerija; Gravenstein, Stefan; Jančorienė, Ligita

    2016-01-01

    Abstract The objective of this study is to describe the clinical and epidemiological characteristics of patients hospitalized in Lithuania who are infected with influenza A(H1N1)pdm09 and to compare pandemic A(H1N1) pdm09 infection with postpandemic. In total, 146 subjects hospitalized with influenza A(H1N1) pdm09 were identified from 2009–2011. There were 53 during the initial pandemic wave in the summer of 2009, 69 during the peak pandemic period, and 24 during the “postpandemic” period that we included in this study. There were 22 subjects who died after laboratory confirmation of influenza A(H1N1)pdm09. No deaths were documented during the first wave. Subjects presenting during the peak of pandemic influenza had a greater incidence of fever (100% vs 77.4%; p<0.001), dry cough (95.7% vs 82.7%; p=0.01), and vomiting (26.1% vs 1.9%, p<0.001) as compared with patients infected during the first wave. The rate of bacterial pneumonia was 18.8% (13/69) during the peak pandemic period and 12.5% (3/24, p=0.754) during the postpandemic period. None of the postpandemic influenza subjects’ intensive care unit stays were due to pneumonia. The hospitalized early 2009 H1N1 pandemic cases and postpandemic cases were milder compared with those at the peak of pandemic activity. PMID:28352819

  15. 2009 H1N1 flu pandemic among professional basketball players: data from 18 countries.

    PubMed

    Kousoulis, Antonis A; Sergentanis, Theodoros N; Tsiodras, Sotirios

    2014-12-01

    Although influenza may be propagated in innumerable occasions and daily situations involving exposure, basketball may create many chances for close contact in which influenza could spread. This study aims to quantify and assess the impact of the 2009 H1N1 influenza pandemic among professional basketball players. A multi-step strategy was followed to gather the relevant data during the 2009-10 basketball season. Possible risk factors were recorded; logistic regression was performed to assess the impact of the former. Where data were only available in the press, cases were also verified by subsequent communication with the national basketball federations. Relevant data were available for 18 countries (218 teams, 3,024 players). In all, 52 H1N1 cases in 19 teams were reported. A larger number of players presented as a risk factor for the emergence of H1N1 cases to a borderline extent (Odds Ratio, OR 1.19, 95% CI 1.00-1.41, p 0.056). A borderline association also implicated the population of the city-basis (OR 1.01, 95% CI 1.00-1.02, p 0.094). On the other hand, no significant association with risk of H1N1 emergence was demonstrated regarding latitude and longitude of the city-basis. Even in environments where the best possible preventive and other medical care is provided influenza continues to be a threat. The microenvironment (crowding index, players per team) seemed to represent the most meaningful predictor regarding H1N1 emergence in a basketball team.

  16. Receptor recognition mechanism of human influenza A H1N1 (1918), avian influenza A H5N1 (2004), and pandemic H1N1 (2009) neuraminidase.

    PubMed

    Jongkon, Nipa; Sangma, Chak

    2012-01-01

    Influenza A neuraminidase (NA) is a target for anti-influenza drugs. The function of this enzyme is to cleave a glycosidic linkage of a host cell receptor that links sialic acid (Sia) to galactose (Gal), to allow the virus to leave an infected cell and propagate. The receptor is an oligosaccharide on the host cell surface. There are two types of oligosaccharide receptor; the first, which is found mainly on avian epithelial cell surfaces, links Sia with Gal by an α2,3 glycosidic linkage; in the second, found mainly on human epithelial cell surfaces, linkage is via an α2,6 linkage. Some researchers believe that NAs from different viruses show selectivity for each type of linkage, but there is limited information available to confirm this hypothesis. To see if the linkage type is more specific to any particular NA, a number of NA-receptor complexes of human influenza A H1N1 (1918), avian influenza A H5N1 (2004), and a pandemic strain of H1N1 (2009) were constructed using homology modeling and molecular dynamics simulation. The results show that the two types of receptor analogues bound to NAs use different mechanisms. Moreover, it was found that a residue unique to avian virus NA is responsible for the recognition of the Siaα2,3Gal receptor, and a residue unique to human virus NA is responsible for the recognition of Siaα2,6Gal. We believe that this finding could explain how NAs of different virus origins always possess some unique residues.

  17. The Genomic Contributions of Avian H1N1 Influenza A Viruses to the Evolution of Mammalian Strains

    PubMed Central

    Wu, Gang; Zhang, Jinghui; Webster, Robert G.

    2015-01-01

    Among the influenza A viruses (IAVs) in wild aquatic birds, only H1, H2, and H3 subtypes have caused epidemics in humans. H1N1 viruses of avian origin have also caused 3 of 5 pandemics. To understand the reappearance of H1N1 in the context of pandemic emergence, we investigated whether avian H1N1 IAVs have contributed to the evolution of human, swine, and 2009 pandemic H1N1 IAVs. On the basis of phylogenetic analysis, we concluded that the polymerase gene segments (especially PB2 and PA) circulating in North American avian H1N1 IAVs have been reintroduced to swine multiple times, resulting in different lineages that led to the emergence of the 2009 pandemic H1N1 IAVs. Moreover, the similar topologies of hemagglutinin and nucleoprotein and neuraminidase and matrix gene segments suggest that each surface glycoprotein coevolved with an internal gene segment within the H1N1 subtype. The genotype of avian H1N1 IAVs of Charadriiformes origin isolated in 2009 differs from that of avian H1N1 IAVs of Anseriformes origin. When the antigenic sites in the hemagglutinin of all 31 North American avian H1N1 IAVs were considered, 60%-80% of the amino acids at the antigenic sites were identical to those in 1918 and/or 2009 pandemic H1N1 viruses. Thus, although the pathogenicity of avian H1N1 IAVs could not be inferred from the phylogeny due to the small dataset, the evolutionary process within the H1N1 IAV subtype suggests that the circulation of H1N1 IAVs in wild birds poses a continuous threat for future influenza pandemics in humans. PMID:26208281

  18. The Genomic Contributions of Avian H1N1 Influenza A Viruses to the Evolution of Mammalian Strains.

    PubMed

    Koçer, Zeynep A; Carter, Robert; Wu, Gang; Zhang, Jinghui; Webster, Robert G

    2015-01-01

    Among the influenza A viruses (IAVs) in wild aquatic birds, only H1, H2, and H3 subtypes have caused epidemics in humans. H1N1 viruses of avian origin have also caused 3 of 5 pandemics. To understand the reappearance of H1N1 in the context of pandemic emergence, we investigated whether avian H1N1 IAVs have contributed to the evolution of human, swine, and 2009 pandemic H1N1 IAVs. On the basis of phylogenetic analysis, we concluded that the polymerase gene segments (especially PB2 and PA) circulating in North American avian H1N1 IAVs have been reintroduced to swine multiple times, resulting in different lineages that led to the emergence of the 2009 pandemic H1N1 IAVs. Moreover, the similar topologies of hemagglutinin and nucleoprotein and neuraminidase and matrix gene segments suggest that each surface glycoprotein coevolved with an internal gene segment within the H1N1 subtype. The genotype of avian H1N1 IAVs of Charadriiformes origin isolated in 2009 differs from that of avian H1N1 IAVs of Anseriformes origin. When the antigenic sites in the hemagglutinin of all 31 North American avian H1N1 IAVs were considered, 60%-80% of the amino acids at the antigenic sites were identical to those in 1918 and/or 2009 pandemic H1N1 viruses. Thus, although the pathogenicity of avian H1N1 IAVs could not be inferred from the phylogeny due to the small dataset, the evolutionary process within the H1N1 IAV subtype suggests that the circulation of H1N1 IAVs in wild birds poses a continuous threat for future influenza pandemics in humans.

  19. Using sentinel surveillance system to monitor seasonal and novel H1N1 influenza infection in Houston, Texas: outcome analysis of 2008-2009 flu season.

    PubMed

    Khuwaja, Salma; Mgbere, Osaro; Awosika-Olumo, Adebowale; Momin, Fayaz; Ngo, Katherine

    2011-10-01

    The advent of the novel H1N1 virus prompted the Houston Department of Health and Human services (HDHHS) to use the existing sentinel surveillance system to effectively monitor the situation of novel H1N1 virus in the Houston metropolitan area. The objective of this study was to evaluate the demographic characteristics and common symptoms associated with confirmed cases of seasonal influenza and Novel H1N1 virus reported to HDHHS between October 2008 and October 2009. A total of 30 providers were randomly selected using the probability proportional to size (PPS) sampling technique to participate in a sentinel surveillance system. The system was used to effectively monitor both seasonal and novel H1N1 virus in the Houston metropolitan area. These providers collected and submitted specimens for testing at HDHHS laboratory from patients with influenza-like illness (ILI) symptoms who visited their clinics during the period, October 2008 and October 2009. These data formed the basis of the current study. Data obtained were subjected to both descriptive and inferential statistical analyses using SAS software version 9.1.3. Overall a total of 1,122 ILI cases were reported to HDHHS by sentinel providers and tested by HDHHS laboratory. Of this number 296 (67.5%) specimens tested positive for influenza A; 140 (32.0%) for influenza B, and 2 (0.46%) for influenza A/B. Two hundred and fifty-nine (59%) were confirmed cases of seasonal influenza and 179 (41%) were novel H1N1 subtype, respectively. The median ages for seasonal influenza and novel H1N1 virus were 7 and 8 years, with majority of the cases reported among children of age 5-9 years. Fever was the most common symptom reported among patients with seasonal flu and novel H1N1 virus, followed by cough. Twenty-three percent (23%) of patients who were vaccinated against seasonal flu prior to the epidemic were infected with seasonal flu virus. The sentinel surveillance system provided timely data on the circulating ILI that

  20. 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

  1. Phylogenetic analyses of influenza A (H1N1)pdm09 hemagglutinin gene during and after the pandemic event in Brazil.

    PubMed

    Resende, Paola Cristina; Motta, Fernando Couto; Born, Priscila Silva; Machado, Daniela; Caetano, Braulia Costa; Brown, David; Siqueira, Marilda Mendonça

    2015-12-01

    Pandemic influenza A H1N1 [A(H1N1)pdm09] was first detected in Brazil in May 2009, and spread extensively throughout the country causing a peak of infection during June to August 2009. Since then, it has continued to circulate with a seasonal pattern, causing high rates of morbidity and mortality. Over this period, the virus has continually evolved with the accumulation of new mutations. In this study we analyze the phylogenetic relationship in a collection of 220 A(H1N1)pdm09 hemagglutinin (HA) gene sequences collected during and after the pandemic period (2009 to 2014) in Brazil. In addition, we have looked for evidence of viral polymorphisms associated with severe disease and compared the range of viral variants with the vaccine strain (A/California/7/2009) used throughout this period. The phylogenetic analyses in this study revealed the circulation of at least eight genetic groups in Brazil. Two (G6-pdm and G7-pdm) co-circulated during the pandemic period, showing an early pattern of viral diversification with a low genetic distance from vaccine strain. Other phylogenetic groups, G5, G6 (including 6B, 6C and 6D subgroups), and G7 were found in the subsequent epidemic seasons from 2011 to 2014. These viruses exhibited more amino acid differences from the vaccine strain with several substitutions at the antigenic sites. This is associated with a theoretical decrease in the vaccine efficacy. Furthermore, we observed that the presence of any polymorphism at residue 222 of the HA gene was significantly associated with severe/fatal cases, reinforcing previous reports that described this residue as a potential virulence marker. This study provides new information about the circulation of some viral variants in Brazil, follows up potential genetic markers associated with virulence and allows infer if the efficacy of the current vaccine against more recent A(H1N1)pdm09 strains may be reduced.

  2. Passive immunity to pandemic H1N1 2009 by swine flu parties.

    PubMed

    Aggarwal, Nitish; Aggarwal, Pushkar

    2009-12-15

    The general population is concerned about the probable devastating effects of pandemic H1N1 2009. Based upon the 1918 Spanish flu pandemic, scientific publications and theories, the idea of swine flu parties to achieve passive immunity against pandemic H1N1 2009 has been proposed. Public health officials have asked the general public not to resort to this method. However, no concrete evidence of the reasoning behind the reco