Farrukh, Muhammad Junaid; Ming, Long Chiau; Zaidi, Syed Tabish Razi; Khan, Tahir Mehmood
Influenza vaccination is strongly recommended by World Health Organisation on a yearly basis. The rate of immunization in Pakistan is suboptimal. High cost, traditional norms, customs and low levels of education in Pakistan are preventing people from getting vaccinated. It is timely to include influenza vaccination in the expanded programme on immunization (EPI), which is a disease prevention programme aiming to eradicate preventable diseases through subsidized or free immunization. The Ministry of National Health Services, Regulation and Coordination, Government of Pakistan should launch a national influenza vaccine policy in view of this current situation and oversee its implementation. Healthcare professionals should promote influenza vaccination and focus on high risk groups such as the elderly, pregnant women and children. Convincing and educating family members regarding immunization of pregnant women and follow-up with parents regarding a second influenza shot for their children will further improve vaccination rates in Pakistan.
Tamura, Shin-Ichi; Ainai, Akira; Suzuki, Tadaki; Kurata, Takeshi; Hasegawa, Hideki
on this parameter. Data suggest that adjuvant-combined nasal-inactivated vaccines have advantages over the current injectable vaccine because the former induce both S-IgA and serum IgG Abs. In addition, nasal-inactivated vaccines seem to be superior to the LAIV vaccines, because non-infectious preparations could be used in high-risk groups. Thus, the development of intranasal inactivated vaccines is recommended, because such vaccines are expected to improve the efficacy of influenza vaccines.
Weber, David J; Orenstein, Walter; Rutala, William A
Influenza causes substantial morbidity and mortality worldwide each year. Healthcare-associated influenza is a frequent event. Health care personnel (HCP) may be the source for infecting patients and may propagate nosocomial outbreaks. All HCP should receive a dose of influenza vaccine each year to protect themselves and others. This commentary will discuss the study recently published in the IJHPR by Nutman and Yoeli which assessed the beliefs and attitudes of HCP in an Israel hospital regarding influenza and the influenza vaccine. Unfortunately, as noted by Nutman and Yoeli in this issue many HCP in Israel choose not to receive influenza immunization and many harbor misconceptions regarding their risk for influenza as well as the benefits of influenza vaccine. We also discuss proven methods to increase acceptance by HCP for receiving an annual influenza vaccine.
Shaw, Alan R
Influenza vaccines have been available since the 1950s and have seen increasingly wide use as public health authorities expanded recommendations. Recent events including shortages and avian influenza outbreaks have renewed interest in influenza vaccines, particularly improved vaccines.
Soleimani, Sina; Shahsavandi, Shahla; Maddadgar, Omid
Immunization with DNA vaccines as a novel alternative to conventional vaccination strategy requires adjuvant for improving vaccine efficacy. The conserved immunogenic HA2 subunit, which harbors neutralizing epitopes is a promising vaccine candidate against influenza viruses. In this study, for the first time we explore the idea of using host interferon inducible Mx protein to increase the immunogenicity of HA2 H9N2 influenza DNA vaccine. The potency and safety of the Mx adjuvanted-HA2 vaccine was evaluated in BALB/c mice by different prime-boost strategies. To assess the effect of the vaccination on the virus clearance rate, mice were challenged with homologous influenza virus. Administration of the adjuvanted vaccine and boosting with the same regimen could effectively enhance both humoral and cellular immune responses in treated mice. These data demonstrated that Mx as host defense peptide can be potentiated for improving influenza vaccine efficacy.
... the recombinant influenza vaccine (RIV). The nasal spray flu vaccine (live attenuated influenza vaccine or LAIV) should NOT ... to your doctor or pharmacist about the best flu vaccine option for you or your family.
Every year, Influenza virus infection is at the origin of substantial excess in morbidity and mortality in developed as well as developing countries. Influenza viruses undergo antigenic drift which cause annual replacement of strain included in classical trivalent vaccines. Less frequently, this virus can also undergo antigenic shift, which corresponds to a major antigenic change and can lead to an extra medical burden. Several vaccines have been made available to immunize individuals against seasonal as well as pandemic influenza viruses. For seasonal Influenza vaccines, live attenuated and classical inactivated trivalent vaccines have been licensed and are widely used. Additionally, several strategies are under investigations to improve further the efficacy of existing seasonal vaccines in children and elderly. These include the use of adjuvant, increase in antigen content, or alternative route of delivery. Similarly, several approaches have been licensed to address additional challenge posed by pandemic viruses. The different vaccination strategies used to maximise protection against seasonal as well as pandemic influenza will be reviewed and discussed in the perspective the current threat posed by the H1N1v pandemic Influenza.
Kim, Hyunsuh; Schoofs, Peter; Anderson, David A; Tannock, Gregory A; Rockman, Steven P
Gene reassortment has proved useful in improving yields of influenza A antigens of egg-based inactivated vaccines, but similar approaches have been difficult with influenza B antigens. Current regulations for influenza vaccine seed viruses limit the number of egg passages and as a result resultant yields from influenza B vaccine seed viruses are frequently inconsistent. Therefore, reliable approaches to enhance yields of influenza B vaccine seed viruses are required for efficient vaccine manufacture. In the present study three stable cold-adapted (ca) mutants, caF, caM and caB derived from seasonal epidemic strains, B/Florida/4/2006, B/Malaysia/2506/2004 and B/Brisbane/60/2008 were prepared, which produced high hemagglutinin antigen yields and also increased viral yields of reassortants possessing the desired 6:2 gene constellation. The results demonstrate that consistent improvements in yields of influenza B viruses can be obtained by cold adaptation following extended passage. Taken together, the three ca viruses were shown to have potential as donor viruses for the preparation of high-yielding influenza B vaccine viruses by reassortment.
Luke, Catherine J; Subbarao, Kanta
A variety of platforms are being explored for the development of vaccines for pandemic influenza. Observations that traditional inactivated subvirion vaccines and live-attenuated vaccines against H5 and some H7 influenza viruses were poorly immunogenic spurred efforts to evaluate new approaches, including whole virus vaccines, higher doses of antigen, addition of adjuvants and combinations of different vaccine modalities in heterologous prime-boost regimens to potentiate immune responses. Results from clinical trials of prime-boost regimens have been very promising. Further studies are needed to determine optimal combinations of platforms, intervals between doses of vaccines and the logistics of deployment in pre-pandemic and early pandemic settings.
Ambrose, Christopher S.; Levin, Myron J.
Two antigenically distinct lineages of influenza B viruses have circulated globally since 1985. However, licensed trivalent seasonal influenza vaccines contain antigens from only a single influenza B virus and thus provide limited immunity against circulating influenza B strains of the lineage not present in the vaccine. In recent years, predictions about which B lineage will predominate in an upcoming influenza season have been no better than chance alone, correct in only 5 of the 10 seasons from 2001 to 2011. Consequently, seasonal influenza vaccines could be improved by inclusion of influenza B strains of both lineages. The resulting quadrivalent influenza vaccines would allow influenza vaccination campaigns to respond more effectively to current global influenza epidemiology. Manufacturing capacity for seasonal influenza vaccines has increased sufficiently to supply quadrivalent influenza vaccines, and methods to identify the influenza B strains to include in such vaccines are in place. Multiple manufacturers have initiated clinical studies of quadrivalent influenza vaccines. Data from those studies, taken together with epidemiologic data regarding the burden of disease caused by influenza B infections, will determine the safety, effectiveness, and benefit of utilizing quadrivalent vaccines for the prevention of seasonal influenza disease. PMID:22252006
Rashid, Harunor; Yin, Jiehui Kevin; Ward, Kirsten; King, Catherine; Seale, Holly; Booy, Robert
Despite official recommendations for health care workers to receive the influenza vaccine, uptake remains low. This systematic review of randomized controlled trials was conducted to understand the evidence about interventions to improve influenza vaccine uptake among health care workers. We identified twelve randomized controlled trials that, collectively, assessed six major categories of interventions involving 193,924 health care workers in high-income countries. The categories were educational materials and training sessions, improved access to the vaccine, rewards following vaccination, organized efforts to raise vaccine awareness, reminders to get vaccinated, and the use of lead advocates for vaccination. Only one of the four studies that evaluated the effect of a single intervention in isolation demonstrated a significantly higher vaccine uptake rate in the intervention group, compared to controls. However, five of the eight studies that evaluated a combination of strategies showed significantly higher vaccine uptake. Despite the low quality of the studies identified, the data suggest that combined interventions can moderately increase vaccine uptake among health care workers. Further methodologically appropriate trials of combined interventions tailored to individual health care settings and incorporating less-studied strategies would enhance the evidence about interventions to improve immunization uptake among health care workers.
Alan, Hampson; Ian, Barr; Nancy, Cox; Ruben O, Donis; Siddhivinayak, Hirve; Daniel, Jernigan; Jacqueline, Katz; John, McCauley; Fernando, Motta; Takato, Odagiri; Tam, John S; Anthony, Waddell; Richard, Webby; Thedi, Ziegler; Wenqing, Zhang
Since 2010 the WHO has held a series of informal consultations to explore ways of improving the currently highly complex and time-pressured influenza vaccine virus selection and development process. In November 2015 experts from around the world met to review the current status of efforts in this field. Discussion topics included strengthening influenza surveillance activities to increase the availability of candidate vaccine viruses and improve the extent, timeliness and quality of surveillance data. Consideration was also given to the development and potential application of newer laboratory assays to better characterize candidate vaccine viruses, the potential importance of antibodies directed against influenza virus neuraminidase, and the role of vaccine effectiveness studies. Advances in next generation sequencing and whole genome sequencing of influenza viruses were also discussed, along with associated developments in synthetic genomics technologies, evolutionary analysis and predictive mathematical modelling. Discussions were also held on the late emergence of an antigenic variant influenza A(H3N2) virus in mid-2014 that could not be incorporated in time into the 2014-15 northern hemisphere vaccine. There was broad recognition that given the current highly constrained influenza vaccine development and production timeline it would remain impossible to incorporate any variant virus which emerged significantly long after the relevant WHO biannual influenza vaccine composition meetings. Discussions were also held on the development of pandemic and broadly protective vaccines, and on associated regulatory and manufacturing requirements and constraints. With increasing awareness of the health and economic burdens caused by seasonal influenza, the ever-present threat posed by zoonotic influenza viruses, and the significant impact of the 2014-15 northern hemisphere seasonal influenza vaccine mismatch, this consultation provided a very timely opportunity to share
Fiore, Anthony E; Bridges, Carolyn B; Cox, Nancy J
Influenza vaccines are the mainstay of efforts to reduce the substantial health burden from seasonal influenza. Inactivated influenza vaccines have been available since the 1940s and are administered via intramuscular injection. Inactivated vaccines can be given to anyone six months of age or older. Live attenuated, cold-adapted influenza vaccines (LAIV) were developed in the 1960s but were not licensed in the United States until 2003, and are administered via nasal spray. Both vaccines are trivalent preparations grown in eggs and do not contain adjuvants. LAIV is licensed for use in the United States for healthy nonpregnant persons 2-49 years of age.Influenza vaccination induces antibodies primarily against the major surface glycoproteins hemagglutinin (HA) and neuraminidase (NA); antibodies directed against the HA are most important for protection against illness. The immune response peaks at 2-4 weeks after one dose in primed individuals. In previously unvaccinated children <9 years of age, two doses of influenza vaccine are recommended, as some children in this age group have limited or no prior infections from circulating types and subtypes of seasonal influenza. These children require both an initial priming dose and a subsequent booster dose of vaccine to mount a protective antibody response.The most common adverse events associated with inactivated vaccines are sore arm and redness at the injection site; systemic symptoms such as fever or malaise are less commonly reported. Guillian-Barré Syndrome (GBS) was identified among approximately 1 per 100,000 recipients of the 1976 swine influenza vaccine. The risk of influenza vaccine-associated GBS from seasonal influenza vaccine is thought to be at most approximately 1-2 cases per 1 million vaccinees, based on a few studies that have found an association; other studies have found no association.The most common adverse events associated with LAIV are nasal congestion, headache, myalgias or fever. Studies of the
Tripp, Ralph A.; Tompkins, S. Mark
Despite the availability of an inactivated vaccine that has been licensed for >50 years, the influenza virus continues to cause morbidity and mortality worldwide. Constant evolution of circulating influenza virus strains and the emergence of new strains diminishes the effectiveness of annual vaccines that rely on a match with circulating influenza strains. Thus, there is a continued need for new, efficacious vaccines conferring cross-clade protection to avoid the need for biannual reformulation of seasonal influenza vaccines. Recombinant virus-vectored vaccines are an appealing alternative to classical inactivated vaccines because virus vectors enable native expression of influenza antigens, even from virulent influenza viruses, while expressed in the context of the vector that can improve immunogenicity. In addition, a vectored vaccine often enables delivery of the vaccine to sites of inductive immunity such as the respiratory tract enabling protection from influenza virus infection. Moreover, the ability to readily manipulate virus vectors to produce novel influenza vaccines may provide the quickest path toward a universal vaccine protecting against all influenza viruses. This review will discuss experimental virus-vectored vaccines for use in humans, comparing them to licensed vaccines and the hurdles faced for licensure of these next-generation influenza virus vaccines. PMID:25105278
Wahlen, Mongeon Kari J; Bessette, Richard R; Bernard, Matthew E; Springer, Donna J; Benson, Catherine A
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.
Wong, Sook-San; Webby, Richard J
The challenges in successful vaccination against influenza using conventional approaches lie in their variable efficacy in different age populations, the antigenic variability of the circulating virus, and the production and manufacturing limitations to ensure safe, timely, and adequate supply of vaccine. The conventional influenza vaccine platform is based on stimulating immunity against the major neutralizing antibody target, hemagglutinin (HA), by virus attenuation or inactivation. Improvements to this conventional system have focused primarily on improving production and immunogenicity. Cell culture, reverse genetics, and baculovirus expression technology allow for safe and scalable production, while adjuvants, dose variation, and alternate routes of delivery aim to improve vaccine immunogenicity. Fundamentally different approaches that are currently under development hope to signal new generations of influenza vaccines. Such approaches target nonvariable regions of antigenic proteins, with the idea of stimulating cross-protective antibodies and thus creating a "universal" influenza vaccine. While such approaches have obvious benefits, there are many hurdles yet to clear. Here, we discuss the process and challenges of the current influenza vaccine platform as well as new approaches that are being investigated based on the same antigenic target and newer technologies based on different antigenic targets.
Houser, Katherine; Subbarao, Kanta
Vaccination is the best method for the prevention and control of influenza. Vaccination can reduce illness and lessen severity of infection. This review focuses on how currently licensed influenza vaccines are generated in the U.S., why the biology of influenza poses vaccine challenges, and vaccine approaches on the horizon that address these challenges. PMID:25766291
Folkins, Chris; Li, Wilson; Zervas, John
Objectives: To describe the demographic characteristics and risk factors of patients receiving influenza vaccination in community pharmacies and to understand patient experiences and perceptions surrounding being vaccinated by a pharmacist. Methods: Survey data were collected by research pharmacists at 4 different community pharmacy locations in Toronto throughout a period of 8 weeks during October and November 2013. Participation in the survey was voluntary, and all patients vaccinated by pharmacists were invited to complete a survey following immunization. Results: During the course of the study, 2498 vaccine doses were administered among all study sites, and 1502 surveys were completed. Our data showed a high degree of patient satisfaction, with 92% of patients indicating they were very satisfied with the pharmacist’s injection technique and the services they received. Furthermore, 86% of patients were very comfortable with being vaccinated by a pharmacist, and 99% of patients reported they would recommend that friends and family be vaccinated by a pharmacist. Convenience and accessibility were major determinants of patient satisfaction, as shown by 46% of all written comments specifically addressing these factors. Of the patients surveyed, 25% were not regular annual vaccine recipients, and 47% were classified as being at high risk for influenza complications according to Public Health Agency of Canada criteria. Notably, 28% of total patients and 21% of high-risk patients reported that they would not have been immunized this year if pharmacy-based vaccination were not available. Conclusions: Our findings suggest that pharmacists provide a highly convenient and accessible option for seasonal flu vaccination that is viewed favourably by patients. Administration of the flu vaccine by pharmacists has the potential to positively affect public health by improving vaccination rates among high-risk patients, first-time or occasional vaccine recipients, and patients
Surveillance for influenza A viruses (IAV) circulating in pigs and other non-human mammals has been chronically underfunded and virtually nonexistent in many areas of the world. In March-April 2009, a novel pandemic H1N1 emerged and demonstrated in a very public forum the paucity of data on influenz...
Song, Jae-Min; Kim, Yeu-Chun; O, Eunju; Compans, Richard W; Prausnitz, Mark R; Kang, Sang-Moo
In this study, we tested the hypothesis that DNA vaccination in the skin using microneedles improves protective immunity compared to conventional intramuscular (IM) injection of a plasmid DNA vaccine encoding the influenza hemagglutinin (HA). In vivo fluorescence imaging demonstrated the expression of a reporter gene delivered to the skin using a solid microneedle patch coated with plasmid DNA. Vaccination at a low dose (3 µg HA DNA) using microneedles generated significantly stronger humoral immune responses and better protective responses post-challenge compared to IM vaccination at either low or high (10 µg HA DNA) dose. Vaccination using microneedles at a high (10 µg) dose further generated improved post-challenge protection, as measured by survival, recall antibody-secreting cell responses in spleen and bone marrow, and interferon (IFN)-γ cytokine T-cell responses. This study demonstrates that DNA vaccination in the skin using microneedles induces higher humoral and cellular immune responses as well as improves protective immunity compared to conventional IM injection of HA DNA vaccine. PMID:22508490
Vassilieva, Elena V.; Kalluri, Haripriya; McAllister, Devin; Taherbhai, Misha T.; Esser, E. Stein; Pewin, Winston P.; Pulit-Penaloza, Joanna A.; Prausnitz, Mark R.; Compans, Richard W.; Skountzou, Ioanna
Prevention of seasonal influenza epidemics and pandemics relies on widespread vaccination coverage to induce protective immunity. In addition to a good antigenic match with the circulating viruses, the effectiveness of individual strains represented in the trivalent vaccines depends on their immunogenicity. In this study we evaluated the immunogenicity of H1N1, H3N2 and B seasonal influenza virus vaccine strains delivered individually with a novel dissolving microneedle patch and the stability of this formulation during storage at 25°C. Our data demonstrate that all strains retained their antigenic activity after incorporation in the dissolving patches as measured by SRID assay and immune responses to vaccination in BALB/c mice. After a single immunization all three antigens delivered with microneedle patches induced superior neutralizing antibody titers compared to intramuscular immunization. Cutaneous antigen delivery was especially beneficial for the less immunogenic B strain. Mice immunized with dissolving microneedle patches encapsulating influenza A/Brisbane/59/07 (H1N1) vaccine were fully protected against lethal challenge by homologous mouse-adapted influenza virus. All vaccine components retained activity during storage at room temperature for at least three months as measured in vitro by SRID assay and in vivo by mouse immunization studies. Our data demonstrate that dissolving microneedle patches are a promising advance for influenza cutaneous vaccination due to improved immune responses using less immunogenic influenza antigens and enhanced stability. PMID:25895053
Vassilieva, Elena V; Kalluri, Haripriya; McAllister, Devin; Taherbhai, Misha T; Esser, E Stein; Pewin, Winston P; Pulit-Penaloza, Joanna A; Prausnitz, Mark R; Compans, Richard W; Skountzou, Ioanna
Prevention of seasonal influenza epidemics and pandemics relies on widespread vaccination coverage to induce protective immunity. In addition to a good antigenic match with the circulating viruses, the effectiveness of individual strains represented in the trivalent vaccines depends on their immunogenicity. In this study, we evaluated the immunogenicity of H1N1, H3N2, and B seasonal influenza virus vaccine strains delivered individually with a novel dissolving microneedle patch and the stability of this formulation during storage at 25 °C. Our data demonstrate that all strains retained their antigenic activity after incorporation in the dissolving patches as measured by single radial diffusion (SRID) assay and immune responses to vaccination in BALB/c mice. After a single immunization, all three antigens delivered with microneedle patches induced superior neutralizing antibody titers compared to intramuscular immunization. Cutaneous antigen delivery was especially beneficial for the less immunogenic B strain. Mice immunized with dissolving microneedle patches encapsulating influenza A/Brisbane/59/07 (H1N1) vaccine were fully protected against lethal challenge by homologous mouse-adapted influenza virus. All vaccine components retained activity during storage at room temperature for at least 3 months as measured in vitro by SRID assay and in vivo by mouse immunization studies. Our data demonstrate that dissolving microneedle patches are a promising advance for influenza cutaneous vaccination due to improved immune responses using less immunogenic influenza antigens and enhanced stability.
Medlock, Jan; Galvani, Alison P
The criteria to assess public health policies are fundamental to policy optimization. Using a model parametrized with survey-based contact data and mortality data from influenza pandemics, we determined optimal vaccine allocation for five outcome measures: deaths, infections, years of life lost, contingent valuation, and economic costs. We find that optimal vaccination is achieved by prioritization of schoolchildren and adults aged 30 to 39 years. Schoolchildren are most responsible for transmission, and their parents serve as bridges to the rest of the population. Our results indicate that consideration of age-specific transmission dynamics is paramount to the optimal allocation of influenza vaccines. We also found that previous and new recommendations from the U.S. Centers for Disease Control and Prevention both for the novel swine-origin influenza and, particularly, for seasonal influenza, are suboptimal for all outcome measures.
Tomar, Jasmine; Born, Philip A; Frijlink, Henderik W; Hinrichs, Wouter L J
Cold-chain requirements, limited stockpiling potential and the lack of potent immune responses are major challenges of parenterally formulated influenza vaccines. Decreased cold chain dependence and stockpiling can be achieved if vaccines are formulated in a dry state using suitable excipients and drying technologies. Furthermore, having the vaccine in a dry state enables the development of non-parenteral patient friendly dosage forms: microneedles for transdermal administration, tablets for oral administration, and powders for epidermal, nasal or pulmonary administration. Moreover, these administration routes have the potential to elicit an improved immune response. This review highlights the rationale for the development of dried influenza vaccines, as well as processes used for the drying and stabilization of influenza vaccines; it also compares the immunogenicity of dried influenza vaccines administered via non-invasive routes with that of parenterally administered influenza vaccines. Finally, it discusses unmet needs, challenges and future developments in the field of dried influenza vaccines.
Lin, Chyongchiou J; Nowalk, Mary Patricia; Toback, Seth L; Rousculp, Matthew D; Raymund, Mahlon; Ambrose, Christopher S; Zimmerman, Richard K
This randomized cluster trial was designed to improve workplace influenza vaccination rates using enhanced advertising, choice of vaccine type (intranasal or injectable) and an incentive. Workers aged 18-49 years were surveyed immediately following vaccination to determine factors associated with vaccination behavior and choice. The questionnaire assessed attitudes, beliefs and social support for influenza vaccine, demographics, and historical, current, and intentional vaccination behavior. Of the 2389 vaccinees, 83.3% received injectable vaccine and 16.7% received intranasal vaccine. Factors associated with previous influenza vaccination were older age, female sex, higher education and greater support for injectable vaccine (all P<.02). Current influenza vaccination with intranasal vaccine vs. injectable vaccine was associated with higher education, the study interventions, greater support for the intranasal vaccine and nasal sprays, less support of injectable vaccine, more negative attitudes about influenza vaccine, and a greater likelihood of reporting that the individual would not have been vaccinated had only injectable vaccine been offered (all P<.01). Intentional vaccine choice was most highly associated with previous vaccination behavior (P<.001). A key to long term improvements in workplace vaccination is to encourage first time influenza vaccination through interventions that include incentives, publicity and vaccine choice.
Mossad, Sherif B
Influenza vaccination remains our best measure to prevent epidemic and pandemic influenza. We must continue to improve vaccination rates for targeted populations. Antiviral options are currently limited to the neuraminidase inhibitors.
Costantino, Claudio; Mazzucco, Walter; Azzolini, Elena; Baldini, Cesare; Bergomi, Margherita; Biafiore, Alessio Daniele; Bianco, Manuela; Borsari, Lucia; Cacciari, Paolo; Cadeddu, Chiara; Camia, Paola; Carluccio, Eugenia; Conti, Andrea; De Waure, Chiara; Di Gregori, Valentina; Fabiani, Leila; Fallico, Roberto; Filisetti, Barbara; Flacco, Maria E; Franco, Elisabetta; Furnari, Roberto; Galis, Veronica; Gallea, Maria R; Gallone, Maria F; Gallone, Serena; Gelatti, Umberto; Gilardi, Francesco; Giuliani, Anna R; Grillo, Orazio C; Lanati, Niccolò; Mascaretti, Silvia; Mattei, Antonella; Micò, Rocco; Morciano, Laura; Nante, Nicola; Napoli, Giuseppe; Nobile, Carmelo; Palladino, Raffaele; Parisi, Salvatore; Passaro, Maria; Pelissero, Gabriele; Quarto, Michele; Ricciardi, Walter; Romano, Gabriele; Rustico, Ennio; Saponari, Anita; Schioppa, Francesco S; Signorelli, Carlo; Siliquini, Roberta; Trabacchi, Valeria; Triassi, Maria; Varetta, Alessia; Ziglio, Andrea; Zoccali, Angela; Vitale, Francesco; Amodio, Emanuele
Although influenza vaccination is recognized to be safe and effective, recent studies have confirmed that immunization coverage among health care workers remain generally low, especially among medical residents (MRs). Aim of the present multicenter study was to investigate attitudes and determinants associated with acceptance of influenza vaccination among Italian MRs. A survey was performed in 2012 on MRs attending post-graduate schools of 18 Italian Universities. Each participant was interviewed via an anonymous, self-administered, web-based questionnaire including questions on attitudes regarding influenza vaccination. A total of 2506 MRs were recruited in the survey and 299 (11.9%) of these stated they had accepted influenza vaccination in 2011–2012 season. Vaccinated MRs were older (P = 0.006), working in clinical settings (P = 0.048), and vaccinated in the 2 previous seasons (P < 0.001 in both seasons). Moreover, MRs who had recommended influenza vaccination to their patients were significantly more compliant with influenza vaccination uptake in 2011–2012 season (P < 0.001). “To avoid spreading influenza among patients” was recognized as the main reason for accepting vaccination by less than 15% of vaccinated MRs. Italian MRs seem to have a very low compliance with influenza vaccination and they seem to accept influenza vaccination as a habit that is unrelated to professional and ethical responsibility. Otherwise, residents who refuse vaccination in the previous seasons usually maintain their behaviors. Promoting correct attitudes and good practice in order to improve the influenza immunization rates of MRs could represent a decisive goal for increasing immunization coverage among health care workers of the future. PMID:24603089
Mooney, Alaina J; Tompkins, S Mark
Influenza A viruses continue to emerge and re-emerge, causing outbreaks, epidemics and occasionally pandemics. While the influenza vaccines licensed for public use are generally effective against seasonal influenza, issues arise with production, immunogenicity, and efficacy in the case of vaccines against pandemic and emerging influenza viruses, and highly pathogenic avian influenza virus in particular. Thus, there is need of improved influenza vaccines and vaccination strategies. This review discusses advances in alternative influenza vaccines, touching briefly on licensed vaccines and vaccine antigens; then reviewing recombinant subunit vaccines, virus-like particle vaccines and DNA vaccines, with the main focus on virus-vectored vaccine approaches. PMID:23440999
Strengthening the influenza vaccine virus selection and development process: Report of the 3rd WHO Informal Consultation for Improving Influenza Vaccine Virus Selection held at WHO headquarters, Geneva, Switzerland, 1-3 April 2014.
Ampofo, William K; Azziz-Baumgartner, Eduardo; Bashir, Uzma; Cox, Nancy J; Fasce, Rodrigo; Giovanni, Maria; Grohmann, Gary; Huang, Sue; Katz, Jackie; Mironenko, Alla; Mokhtari-Azad, Talat; Sasono, Pretty Multihartina; Rahman, Mahmudur; Sawanpanyalert, Pathom; Siqueira, Marilda; Waddell, Anthony L; Waiboci, Lillian; Wood, John; Zhang, Wenqing; Ziegler, Thedi
Despite long-recognized challenges and constraints associated with their updating and manufacture, influenza vaccines remain at the heart of public health preparedness and response efforts against both seasonal and potentially pandemic influenza viruses. Globally coordinated virological and epidemiological surveillance is the foundation of the influenza vaccine virus selection and development process. Although national influenza surveillance and reporting capabilities are being strengthened and expanded, sustaining and building upon recent gains has become a major challenge. Strengthening the vaccine virus selection process additionally requires the continuation of initiatives to improve the timeliness and representativeness of influenza viruses shared by countries for detailed analysis by the WHO Global Influenza Surveillance and Response System (GISRS). Efforts are also continuing at the national, regional, and global levels to better understand the dynamics of influenza transmission in both temperate and tropical regions. Improved understanding of the degree of influenza seasonality in tropical countries of the world should allow for the strengthening of national vaccination policies and use of the most appropriate available vaccines. There remain a number of limitations and difficulties associated with the use of HAI assays for the antigenic characterization and selection of influenza vaccine viruses by WHOCCs. Current approaches to improving the situation include the more-optimal use of HAI and other assays; improved understanding of the data produced by neutralization assays; and increased standardization of serological testing methods. A number of new technologies and associated tools have the potential to revolutionize influenza surveillance and response activities. These include the increasingly routine use of whole genome next-generation sequencing and other high-throughput approaches. Such approaches could not only become key elements in outbreak
... die from flu, and many more are hospitalized.Flu vaccine can:keep you from getting flu, make flu ... inactivated or recombinant influenza vaccine?A dose of flu vaccine is recommended every flu season. Children 6 months ...
Zhang, Naru; Zheng, Bo-Jian; Lu, Lu; Zhou, Yusen; Jiang, Shibo; Du, Lanying
The ongoing threat of influenza epidemics and pandemics has emphasized the importance of developing safe and effective vaccines against infections from divergent influenza viruses. In this review, we first introduce the structure and life cycle of influenza A viruses, describing major influenza A virus-caused pandemics. We then compare different types of influenza vaccines and discuss current advancements in the development of subunit influenza vaccines, particularly those based on nucleoprotein (NP), extracellular domain of matrix protein 2 (M2e) and hemagglutinin (HA) proteins. We also illustrate potential strategies for improving the efficacy of subunit influenza vaccines. PMID:25529753
Neuzil, Kathleen M; Tsvetnitsky, Vadim; Nyari, Linda J; Bright, Rick A; Boslego, John W
The 2009 influenza A/H1N1 pandemic demonstrated that a pandemic influenza virus has the potential to spread more rapidly in today's highly interconnected world than in the past. While pandemic morbidity and mortality are likely to be greatest in low-resource countries, manufacturing capacity and access to influenza vaccines predominantly exist in countries with greater resources and infrastructure. Even with recently expanded manufacturing capacity, the number of doses available within a 6-month timeframe would be inadequate to fully immunize the global population if the decision to implement a global vaccination program were made today. Improved, affordable vaccines are needed to limit the consequences of a global influenza outbreak and protect low-resource populations. PATH's Influenza Vaccine Project is supporting a range of activities in collaboration with private- and public-sector partners to advance the development of promising influenza vaccines that can be accessible and affordable for people in low-resource countries.
Heinrichs, D; Sennekamp, J; Kirsten, A; Kirsten, D
Allergic alveolitis as a side effect of vaccination is very rare. We report a life-threatening complication in a female patient after influenza vaccination. The causative antigen was the influenza virus itself. Our Patient has suffered from exogen-allergic alveolitis for 12 years. Because of the guidelines of regular administration of influenza vaccination in patients with chronic pulmonary disease further research in patients with known exogen-allergic alveolitis is vitally important for the pharmaceutical drug safety.
Influenza bivalent vaccine comprising recombinant H3 hemagglutinin (HA) and H1 HA containing replaced H3 hemagglutinin transmembrane domain exhibited improved heterosubtypic protection immunity in mice.
Liu, Qiliang; Xue, Chunyi; Zheng, Jing; Liu, Kang; Wang, Yang; Wei, Ying; Liu, George Dacai; Cao, Yongchang
Influenza caused by infection of influenza viruses is still a leading cause of morbidity and mortality in human. Vaccination is the main defense against influenza virus, but current influenza trivalent or quatrivalent vaccines (TIV/QIV) would lose their effectiveness when vaccine strains are mismatched with circulating strains. Our early study showed that recombinant influenza Hx-TM HA proteins containing H3 HA transmembrane domain(TM) had improved immunogenicity and heterosubtypic protection over corresponding wild-type Hx-WT HA proteins. In present study, bivalent vaccines containing H3-WT+Hx-TM were investigated for their immune responses and heterosubtypic protection immunities. The data showed that the bivalent vaccines containing H3-WT and H5-TM or H1-TM had improved immune responses and heterosubtypic protection over the bivalent vaccines containing H3-WT and H5-WT or H1-WT respectively. These results demonstrated that the improved immune responses and heterosubtypic protection of Hx-TM HA proteins could be translated into bivalent vaccines, suggesting a feasible strategy of improving the immune responses and heterosubtypic protection of influenza multivalent vaccines such as TIV and QIV.
Aguilar-Díaz, Fatima Del Carmen; Jiménez-Corona, Maria Eugenia; Ponce-de-León-Rosales, Samuel
We undertook this study to review attitudes, beliefs and practices of healthcare workers (HCW) toward pandemic influenza A vaccine (H1N1) 2009 reported in the literature. Relevant papers published from 2009-2011 reporting attitudes, beliefs and practices of HCW towards pandemic influenza vaccine were identified. Variables such as age, gender, profession, work place area, and previous vaccination uptake were analyzed. In this study, 30 articles regarding attitudes and beliefs toward pandemic influenza vaccination, vaccine uptake and intention to accept vaccine were analyzed. Most studies were cross-sectional in design. Vaccination intention and uptake varies among different countries, 13.5-89.0% and 7.5-63.0%, respectively. Most common reasons for rejection were fear of adverse events, doubt regarding efficacy, not feeling as belonging to a high-risk group and believing that influenza is not a serious illness. Physicians show more favorable attitudes compared to nurses. The main predictor of vaccine uptake was having received previous influenza vaccination. Pandemic influenza uptake was low in most countries. The main reason among HCW for rejection was concern regarding side effects. It is necessary to establish educational programs to provided reliable information and raise awareness of HCW about vaccine use so that they can act as vaccine promoters among the general population.
Vaccines against avian influenza (AI) have had more limited use in poultry than vaccines against other poultry diseases such as Newcastle disease (ND) and infectious bronchitis, and have been used more commonly in the developing world. Over the past 40 years, AI vaccines have been primarily based o...
Lu, Jihu; Wu, Peipei; Zhang, Xuehua; Feng, Lei; Dong, Bin; Chu, Xuan; Liu, Xiufan; Peng, Daxin; Liu, Yuan; Ma, Huailiang; Hou, Jibo; Tang, Yinghua
Combination of CVCVA5 adjuvant and commercial avian influenza (AI) vaccine has been previously demonstrated to provide good protection against different AI viruses in chickens. In this study, we further investigated the protective immunity of CVCVA5-adjuvanted oil-emulsion inactivated AI vaccine in chickens, ducks and geese. Compared to the commercial H5 inactivated vaccine, the H5-CVCVA5 vaccine induced significantly higher titers of hemaglutinin inhibitory antibodies in three lines of broiler chickens and ducks, elongated the antibody persistence periods in geese, elevated the levels of cross serum neutralization antibody against different clade and subclade H5 AI viruses in chicken embryos. High levels of mucosal antibody were detected in chickens injected with the H5 or H9-CVCA5 vaccine. Furthermore, cellular immune response was markedly improved in terms of increasing the serum levels of cytokine interferon-γ and interleukine 4, promoting proliferation of splenocytes and upregulating cytotoxicity activity in both H5- and H9-CVCVA5 vaccinated chickens. Together, these results provide evidence that AI vaccines supplemented with CVCVA5 adjuvant is a promising approach for overcoming the limitation of vaccine strain specificity of protection.
Settembre, Ethan C; Dormitzer, Philip R; Rappuoli, Rino
The recent H7N9 influenza outbreak in China highlights the need for influenza vaccine production systems that are robust and can quickly generate substantial quantities of vaccines that target new strains for pandemic and seasonal immunization. Although the influenza vaccine system, a public-private partnership, has been effective in providing vaccines, there are areas for improvement. Technological advances such as mammalian cell culture production and synthetic vaccine seeds provide a means to increase the speed and accuracy of targeting new influenza strains with mass-produced vaccines by dispensing with the need for egg isolation, adaptation, and reassortment of vaccine viruses. New influenza potency assays that no longer require the time-consuming step of generating sheep antisera could further speed vaccine release. Adjuvants that increase the breadth of the elicited immune response and allow dose sparing provide an additional means to increase the number of available vaccine doses. Together these technologies can improve the influenza vaccination system in the near term. In the longer term, disruptive technologies, such as RNA-based flu vaccines and 'universal' flu vaccines, offer a promise of a dramatically improved influenza vaccine system.
van den Berg, Thierry; Lambrecht, Bénédicte; Marché, Sylvie; Steensels, Mieke; Van Borm, Steven; Bublot, Michel
Although it is well accepted that the present Asian H5N1 panzootic is predominantly an animal health problem, the human health implications and the risk of human pandemic have highlighted the need for more information and collaboration in the field of veterinary and human health. H5 and H7 avian influenza (AI) viruses have the unique property of becoming highly pathogenic (HPAI) during circulation in poultry. Therefore, the final objective of poultry vaccination against AI must be eradication of the virus and the disease. Actually, important differences exist in the control of avian and human influenza viruses. Firstly, unlike human vaccines that must be adapted to the circulating strain to provide adequate protection, avian influenza vaccination provides broader protection against HPAI viruses. Secondly, although clinical protection is the primary goal of human vaccines, poultry vaccination must also stop transmission to achieve efficient control of the disease. This paper addresses these differences by reviewing the current and future influenza vaccines and vaccination strategies in birds.
... Past Newsletters Selecting Viruses for the Seasonal Influenza Vaccine Language: English EspaÃ±ol Recommend on Facebook Tweet ... influence which viruses are selected for use in vaccine production? The influenza viruses in the seasonal flu ...
Ridenour, Callie; Johnson, Adam; Winne, Emily; Hossain, Jaber; Mateu-Petit, Guaniri; Balish, Amanda; Santana, Wanda; Kim, Taejoong; Davis, Charles; Cox, Nancy J; Barr, John R; Donis, Ruben O; Villanueva, Julie; Williams, Tracie L; Chen, Li-Mei
Background The emergence of avian influenza A(H7N9) virus in poultry causing zoonotic human infections was reported on March 31, 2013. Development of A(H7N9) candidate vaccine viruses (CVV) for pandemic preparedness purposes was initiated without delay. Candidate vaccine viruses were derived by reverse genetics using the internal genes of A/Puerto/Rico/8/34 (PR8). The resulting A(H7N9) CVVs needed improvement because they had titers and antigen yields that were suboptimal for vaccine manufacturing in eggs, especially in a pandemic situation. Methods Two CVVs derived by reverse genetics were serially passaged in embryonated eggs to improve the hemagglutinin (HA) antigen yield. The total viral protein and HA antigen yields of six egg-passaged CVVs were determined by the BCA assay and isotope dilution mass spectrometry (IDMS) analysis, respectively. CVVs were antigenically characterized by hemagglutination inhibition (HI) assays with ferret antisera. Results Improvement of total viral protein yield was observed for the six egg-passaged CVVs; HA quantification by IDMS indicated approximately a twofold increase in yield of several egg-passaged viruses as compared to that of the parental CVV. Several different amino acid substitutions were identified in the HA of all viruses after serial passage. However, HI tests indicated that the antigenic properties of two CVVs remained unchanged. Conclusions If influenza A(H7N9) viruses were to acquire sustained human-to-human transmissibility, the improved HA yield of the egg-passaged CVVs generated in this study could expedite vaccine manufacturing for pandemic mitigation. PMID:25962412
Costantino, Claudio; Mazzucco, Walter; Azzolini, Elena; Baldini, Cesare; Bergomi, Margherita; Biafiore, Alessio Daniele; Bianco, Manuela; Borsari, Lucia; Cacciari, Paolo; Cadeddu, Chiara; Camia, Paola; Carluccio, Eugenia; Conti, Andrea; De Waure, Chiara; Di Gregori, Valentina; Fabiani, Leila; Fallico, Roberto; Filisetti, Barbara; Flacco, Maria E; Franco, Elisabetta; Furnari, Roberto; Galis, Veronica; Gallea, Maria R; Gallone, Maria F; Gallone, Serena; Gelatti, Umberto; Gilardi, Francesco; Giuliani, Anna R; Grillo, Orazio C; Lanati, Niccolò; Mascaretti, Silvia; Mattei, Antonella; Micò, Rocco; Morciano, Laura; Nante, Nicola; Napoli, Giuseppe; Nobile, Carmelo Giuseppe; Palladino, Raffaele; Parisi, Salvatore; Passaro, Maria; Pelissero, Gabriele; Quarto, Michele; Ricciardi, Walter; Romano, Gabriele; Rustico, Ennio; Saponari, Anita; Schioppa, Francesco S; Signorelli, Carlo; Siliquini, Roberta; Trabacchi, Valeria; Triassi, Maria; Varetta, Alessia; Ziglio, Andrea; Zoccali, Angela; Vitale, Francesco; Amodio, Emanuele
Although influenza vaccination is recognized to be safe and effective, recent studies have confirmed that immunization coverage among health care workers remain generally low, especially among medical residents (MRs). Aim of the present multicenter study was to investigate attitudes and determinants associated with acceptance of influenza vaccination among Italian MRs. A survey was performed in 2012 on MRs attending post-graduate schools of 18 Italian Universities. Each participant was interviewed via an anonymous, self-administered, web-based questionnaire including questions on attitudes regarding influenza vaccination. A total of 2506 MRs were recruited in the survey and 299 (11.9%) of these stated they had accepted influenza vaccination in 2011-2012 season. Vaccinated MRs were older (P = 0.006), working in clinical settings (P = 0.048), and vaccinated in the 2 previous seasons (P<0.001 in both seasons). Moreover, MRs who had recommended influenza vaccination to their patients were significantly more compliant with influenza vaccination uptake in 2011-2012 season (P<0.001). "To avoid spreading influenza among patients" was recognized as the main reason for accepting vaccination by less than 15% of vaccinated MRs. Italian MRs seem to have a very low compliance with influenza vaccination and they seem to accept influenza vaccination as a habit that is unrelated to professional and ethical responsibility. Otherwise, residents who refuse vaccination in the previous seasons usually maintain their behaviors. Promoting correct attitudes and good practice in order to improve the influenza immunization rates of MRs could represent a decisive goal for increasing immunization coverage among health care workers of the future.
Shope, Richard E.
Either living or heat-killed H. influenzae suis vaccines, given intramuscularly to swine, elicit an immune response capable of modifying the course of a later swine influenza infection. The protection afforded is only partial and is in no way comparable to the complete immunity afforded by swine influenza virus vaccines. PMID:19870654
Ping, Jihui; Lopes, Tiago J S; Neumann, Gabriele; Kawaoka, Yoshihiro
The burden of human infections with influenza A and B viruses is substantial, and the impact of influenza B virus infections can exceed that of influenza A virus infections in some seasons. Over the past few decades, viruses of two influenza B virus lineages (Victoria and Yamagata) have circulated in humans, and both lineages are now represented in influenza vaccines, as recommended by the World Health Organization. Influenza B virus vaccines for humans have been available for more than half a century, yet no systematic efforts have been undertaken to develop high-yield candidates. Therefore, we screened virus libraries possessing random mutations in the six "internal" influenza B viral RNA segments [i.e., those not encoding the major viral antigens, hemagglutinin (HA) and neuraminidase NA)] for mutants that confer efficient replication. Candidate viruses that supported high yield in cell culture were tested with the HA and NA genes of eight different viruses of the Victoria and Yamagata lineages. We identified combinations of mutations that increased the titers of candidate vaccine viruses in mammalian cells used for human influenza vaccine virus propagation and in embryonated chicken eggs, the most common propagation system for influenza viruses. These influenza B virus vaccine backbones can be used for improved vaccine virus production.
Mass in ovo vaccination with live attenuated viruses is widely used in the poultry industry to protect against various infectious diseases. The worldwide outbreaks of low pathogenic and highly pathogenic avian influenza highlight the pressing need for the development of similar mass vaccination strategies against avian influenza viruses. We have previously shown that a genetically modified live attenuated avian influenza virus (LAIV) was amenable for in ovo vaccination and provided optimal protection against H5 HPAI viruses. However, in ovo vaccination against other subtypes resulted in poor hatchability and, therefore, seemed impractical. In this study, we modified the H7 and H9 hemagglutinin (HA) proteins by substituting the amino acids at the cleavage site for those found in the H6 HA subtype. We found that with this modification, a single dose in ovo vaccination of 18-day old eggs provided complete protection against homologous challenge with low pathogenic virus in ≥70% of chickens at 2 or 6 weeks post-hatching. Further, inoculation of 19-day old egg embryos with 106 EID50 of LAIVs improved hatchability to ≥90% (equivalent to unvaccinated controls) with similar levels of protection. Our findings indicate that the strategy of modifying the HA cleavage site combined with the LAIV backbone could be used for in ovo vaccination against avian influenza. Importantly, with protection conferred as early as 2 weeks post-hatching, with this strategy birds would be protected prior to or at the time of delivery to a farm or commercial operation. PMID:21255403
de Vries, R D; Altenburg, A F; Rimmelzwaan, G F
The extensive antigenic drift displayed by seasonal influenza viruses and the risk of pandemics caused by newly emerging antigenically distinct influenza A viruses of novel subtypes has raised considerable interest in the development of so-called universal influenza vaccines. We review options for the development of universal flu vaccines and discuss progress that has been made recently.
Ampofo, William K.; Baylor, Norman; Cobey, Sarah; Cox, Nancy J.; Daves, Sharon; Edwards, Steven; Ferguson, Neil; Grohmann, Gary; Hay, Alan; Katz, Jacqueline; Kullabutr, Kornnika; Lambert, Linda; Levandowski, Roland; Mishra, A. C.; Monto, Arnold; Siqueira, Marilda; Tashiro, Masato; Waddell, Anthony L.; Wairagkar, Niteen; Wood, John; Zambon, Maria; Zhang, Wenqing
Executive summary • For almost 60 years, the WHO Global Influenza Surveillance and Response System (GISRS) has been the key player in monitoring the evolution and spread of influenza viruses and recommending the strains to be used in human influenza vaccines. The GISRS has also worked to continually monitor and assess the risk posed by potential pandemic viruses and to guide appropriate public health responses.• The expanded and enhanced role of the GISRS following the adoption of the International Health Regulations (2005), recognition of the continuing threat posed by avian H5N1 and the aftermath of the 2009 H1N1 pandemic provide an opportune time to critically review the process by which influenza vaccine viruses are selected. In addition to identifying potential areas for improvement, such a review will also help to promote greater appreciation by the wider influenza and policy‐making community of the complexity of influenza vaccine virus selection.• The selection process is highly coordinated and involves continual year‐round integration of virological data and epidemiological information by National Influenza Centres (NICs), thorough antigenic and genetic characterization of viruses by WHO Collaborating Centres (WHOCCs) as part of selecting suitable candidate vaccine viruses, and the preparation of suitable reassortants and corresponding reagents for vaccine standardization by WHO Essential Regulatory Laboratories (ERLs).• Ensuring the optimal effectiveness of vaccines has been assisted in recent years by advances in molecular diagnosis and the availability of more extensive genetic sequence data. However, there remain a number of challenging constraints including variations in the assays used, the possibility of complications resulting from non‐antigenic changes, the limited availability of suitable vaccine viruses and the requirement for recommendations to be made up to a year in advance of the peak of influenza season because of
... is taken in its entirety from the CDC Influenza Live, Intranasal Flu Vaccine Information Statement (VIS): www.cdc.gov/vaccines/ ... flulive.html . CDC review information for Live, Intranasal Influenza VIS: Vaccine Information Statement Influenza Page last reviewed: ...
Mosterín Höpping, Ana; Fonville, Judith M; Russell, Colin A; James, Sarah; Smith, Derek J
Epidemics of seasonal influenza viruses cause considerable morbidity and mortality each year. Various types and subtypes of influenza circulate in humans and evolve continuously such that individuals at risk of serious complications need to be vaccinated annually to keep protection up to date with circulating viruses. The influenza vaccine in most parts of the world is a trivalent vaccine, including an antigenically representative virus of recently circulating influenza A/H3N2, A/H1N1, and influenza B viruses. However, since the 1970s influenza B has split into two antigenically distinct lineages, only one of which is represented in the annual trivalent vaccine at any time. We describe a lineage selection strategy that optimizes protection against influenza B using the standard trivalent vaccine as a potentially cost effective alternative to quadrivalent vaccines.
Limited production capacity and delays in vaccine development are major obstacles to vaccination programs that are designed to mitigate a pandemic influenza. In order to evaluate and compare the impact of various vaccination strategies during a pandemic influenza, we developed an age/risk-structured model of influenza transmission, and parameterized it with epidemiological data from the 2009 H1N1 influenza A pandemic. Our model predicts that the impact of vaccination would be considerably diminished by delays in vaccination and staggered vaccine supply. Nonetheless, prioritizing limited H1N1 vaccine to individuals with a high risk of complications, followed by school-age children, and then preschool-age children, would minimize an over-all attack rate as well as hospitalizations and deaths. This vaccination scheme would maximize the benefits of vaccination by protecting the high-risk people directly, and generating indirect protection by vaccinating children who are most likely to transmit the disease. PMID:21361402
Influenza is associated with substantial morbidity and mortality each year in the United States. From 1976 to 2007, annual deaths from influenza ranged from approximately 3,300 to 49,000. Vaccination against influenza has been recommended to prevent illness and related complications, and since 2010, the Advisory Committee on Immunization Practices has recommended that all persons aged ≥6 months be vaccinated against influenza each year. In 2013, CDC published a model to quantify the annual number of influenza-associated illnesses and hospitalizations averted by influenza vaccination during the 2006-11 influenza seasons. Using that model with 2012-13 influenza season vaccination coverage rates, influenza vaccine effectiveness, and influenza hospitalization rates, CDC estimated that vaccination resulted in 79,000 (17%) fewer hospitalizations during the 2012-13 influenza season than otherwise might have occurred. Based on estimates of the percentage of influenza illnesses that involve hospitalization or medical attention, vaccination also prevented approximately 6.6 million influenza illnesses and 3.2 million medically attended illnesses. Influenza vaccination during the 2012-13 season produced a substantial reduction in influenza-associated illness. However, fewer than half of persons aged ≥6 months were vaccinated. Higher vaccination rates would have resulted in prevention of a substantial number of additional cases and hospitalizations.
Altay, Fatma Aybala; Güz, Galip; Altay, Mustafa
abstract A peritoneal dialysis patient who experienced a repeating attack after a vaccination for influenza while she was being followed and treated succesfully for subacute thyroiditis (SAT) is presented. This case shows SAT as a rare condition following vaccination.. Thus, SAT should be considered as a possible outcome following influenza vaccination and flu-like syndrome. PMID:26809709
Painter, Julia E.; Sales, Jessica M.; Pazol, Karen; Wingood, Gina M.; Windle, Michael; Orenstein, Walter A.; DiClemente, Ralph J.
Background: School-based vaccination programs may provide an effective strategy to immunize adolescents against influenza. This study examined whether adolescent attitudes toward influenza vaccination mediated the relationship between receipt of a school-based influenza vaccination intervention and vaccine uptake. Methods: Participants were…
McLennan, Stuart; Wicker, Sabine
Despite all that is known about the dangers of nosocomial transmission of influenza to the vulnerable patient populations in our healthcare facilities, and the benefits of the influenza vaccination, the low rates of influenza vaccination among healthcare workers (HCWs) internationally shows no sign of significant improvement. With the current voluntary 'opt-in' programmes clearly failing to adequately address this issue, the time has undoubtedly come for a new approach to vaccination to be implemented. Two different approaches to vaccination delivery have been suggested to rectify this situation, mandatory vaccination and 'opt-out' declination forms. It is suggested, however, that these two approaches are inadequate when used by themselves. In order to protect the most vulnerable patients in our healthcare facilities as best we can from serious harm or death caused by nosocomial transmission of influenza, while at the same time respecting HCWs autonomy, and in many jurisdictions, the related legal right to refuse medical treatment, it is recommended that 'op-out' declination forms should be used in conjunction with restricted mandatory vaccination. This 'combined' approach would allow any HCW to refuse the influenza vaccination, but would make the influenza vaccination a mandatory requirement for working in areas where the most vulnerable patients are cared for. Those HCWs not willing to be vaccinated should be required to work in other areas of healthcare.
Pregliasco, F.; Sodano, L.; Mensi, C.; Selvaggi, M. T.; Adamo, B.; D'Argenio, P.; Giussani, F.; Simonetti, A.; Carosella, M. R.; Simeone, R.; Dentizi, C.; Montanaro, C.; Ponzio, G.
This article surveys the attitudes and perceptions of a random sample of the elderly population in three regions of Italy on the use and efficacy of influenza vaccine. The data were collected by direct interviews using a standard questionnaire. The results show that vaccination coverage against influenza is inadequate (26-48.6%). The major reasons for nonvaccination were lack of faith in the vaccine and disbelief that influenza is a dangerous illness. These data emphasize the need for a systematic education programme targeted at the elderly and the provision of influenza vaccination, with the increased cooperation of general practitioners. PMID:10083710
de Vries, Rory D; Altenburg, Arwen F; Rimmelzwaan, Guus F
Currently used influenza vaccines are only effective when the vaccine strains match the epidemic strains antigenically. To this end, seasonal influenza vaccines must be updated almost annually. Furthermore, seasonal influenza vaccines fail to afford protection against antigenically distinct pandemic influenza viruses. Because of an ever-present threat of the next influenza pandemic and the continuous emergence of drift variants of seasonal influenza A viruses, there is a need for an universal influenza vaccine that induces protective immunity against all influenza A viruses. Here, we summarize some of the efforts that are ongoing to develop universal influenza vaccines.
Alvarez, I; Corral, J; Arranz, A; Foruria, A; Landa, V; Lejarza, J R; Marijuán, L; Martínez, J M
The present study investigated the level of immunity of the population against three strains of the influenza virus (A Chile/1/83 -A Philippines/2/82 and B URSS/100/83) before and three months after vaccination, and the immune response to whole virus vaccine as compared with fragmented virus vaccine. A high percentage of the population had titers greater than or equal to 1/10 before vaccination for the Chile (54%) and Philippines (65.7%) strains, while titers against the URSS strain were lower (25.4%). There was a definitive increase in antibody titer in the vaccinated population, although it was lower than expected. The overall response to both vaccines, with protecting titers greater than or equal to 1/40 after vaccination was 65.2% for the Chile strain, 74.6% for the Philippines strain, and 15% for the URSS strain. No differences in the overall immune response were found between the groups vaccinated with whole and fragmented virus.
Patterson, Jan E.; Cadena, Jose; Prigmore, Teresa; Bowling, Jason; Ayala, Beth Ann; Kirkman, Leni; Parekh, Amruta; Scepanski, Theresa
Significant gaps in quality and patient safety in the US health-care system have been identified and were reported in the past decade by the Institute of Medicine. Despite recognition of these gaps in “knowing versus doing,” change in health care is slow and difficult. The quality improvement and clinical safety movement is increasing among US medical centers. Our health science center implemented the UT System Clinical Safety and Effectiveness course, providing project-based teaching of quality-improvement tools and principles of patient safety. A quality-improvement project that increased healthcare workers' influenza vaccination rate by 17.8% from that in 2008 to a rate of 76.6% in 2009 serves as a paradigm of how physicians can lead quality-improvement project teams to narrow the quality chasm (1). Local efforts to narrow the chasm are discussed in the present paper, including inter-professional education in quality improvement and clinical safety. PMID:21686222
Mossad, Sherif B
Faced with a shortage of the inactivated intramuscular influenza vaccine this year, the Centers for Disease Control and Prevention (CDC) has revised its guidelines for immunization and use of antiviral agents. The most rational solution at this time is to direct the supply of scarce vaccine to patients at highest risk of influenza-related complications.
Hirota, Yoshio; Kaji, Masaro
In 1976, influenza mass vaccination among schoolchildren was started under the Preventive Vaccination Law, which was intended to control epidemics in the community. However, in the late 1980s, questions about this policy and vaccine efficacy arose, and a campaign against vaccination began. In 1994, influenza was excluded from the target diseases list in the Preventive Vaccination Law, without considering the immunization policy with respect to the common indications in high-risk groups. In 2001, the Law was again amended, specifying target groups, such as the elderly aged 65 or over, for influenza vaccination. In the 2005--2006 season, vaccine coverage among the elderly reached 52%. This shows that the need for vaccination has gradually become understood. However, the anti-vaccination campaign, which claims that the influenza vaccine has no efficacy, is still active. Vaccine efficacy studies that were not properly conducted are also being reported. In 2002, the Ministry of Health, Labor, and Welfare organized a research group on vaccine efficacy consisting of epidemiologists. The present symposium, as part of the 9th Annual Meeting of the Japanese Society for Vaccinology in 2005, was planned to further introduce epidemiological concepts useful in studying influenza vaccine efficacy.
... HUMAN SERVICES Office of the Secretary Pandemic Influenza Vaccines--Amendment ACTION: Notice of... influenza vaccines, which has been amended a number of times. The original pandemic influenza vaccine... (2010). The major actions taken by this pandemic influenza vaccine declaration are the following:...
Greenberg, David P; Robertson, Corwin A; Gordon, Daniel M
Influenza and dengue are viral illnesses of global public health importance, especially among children. Accordingly, these diseases have been the focus of efforts to improve their prevention and control. Influenza vaccination offers the best protection against clinical disease caused by strains contained within the specific year's formulation. It is not uncommon for there to be a mismatch between vaccine strains and circulating strains, particularly with regards to the B lineages. For more than a decade, two distinct lineages of influenza B (Yamagata and Victoria) have co-circulated in the US with varying frequencies, but trivalent influenza vaccines contain only one B-lineage strain and do not offer adequate protection against the alternate B-lineage. Quadrivalent influenza vaccines (QIVs), containing two A strains (H1N1 and H3N2) and two B strains (one from each lineage) have been developed to help protect against the four strains predicted to be the most likely to be circulating. The QIV section of this article discusses epidemiology of pediatric influenza, importance of influenza B in children, potential benefits of QIV, and new quadrivalent vaccines. In contrast to influenza, a vaccine against dengue is not yet available in spite of many decades of research and development. A global increase in reports of dengue fever (DF) and its more severe presentations, dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS), suggest that US physicians will increasingly encounter patients with this disease. Similarities of the early signs and symptoms of influenza and dengue and the differences in disease management necessitates a better understanding of the epidemiology, clinical presentation, management, and prevention of DF by US physicians, including pediatricians. The article also provides a brief overview of dengue and discusses dengue vaccine development.
There have been 32 epizootics of high pathogenicity avian influenza (HPAI) in birds since 1959. The largest has been the H5N1 HPAI panzootic that emerged in China during 1996 and has spread to infect poultry and/or wild birds in 62 countries during the past 17 years. The majority of the outbreaks oc...
Gill, Harvinder S; Kang, Sang-Moo; Quan, Fu-Shi; Compans, Richard W
Introduction Most vaccines are administered by intramuscular injection using a hypodermic needle and syringe. Some limitations of this procedure include reluctance to be immunized because of fear of needlesticks, and concerns associated with the safe disposal of needles after their use. Skin delivery is an alternate route of vaccination that has potential to be painless and could even lead to dose reduction of vaccines. Recently, microneedles have emerged as a novel painless approach for delivery of influenza vaccines via the skin. Areas covered In this review, we briefly summarize the approaches and devices used for skin vaccination, and then focus on studies of skin immunization with influenza vaccines using microneedles. We discuss both the functional immune response and the nature of this immune response following vaccination with microneedles. Expert opinion The cutaneous administration of influenza vaccines using microneedles offers several advantages: it is painless, elicits stronger immune responses in preclinical studies and could improve responses in high-risk populations. These dry formulations of vaccines provide enhanced stability, a property of high importance in enabling their rapid global distribution in response to possible outbreaks of pandemic influenza and newly emerging infectious diseases. PMID:24521050
Wiersma, Lidewij C. M.; Rimmelzwaan, Guus F.; de Vries, Rory D.
Influenza viruses have a huge impact on public health. Current influenza vaccines need to be updated annually and protect poorly against antigenic drift variants or novel emerging subtypes. Vaccination against influenza can be improved in two important ways, either by inducing more broadly protective immune responses or by decreasing the time of vaccine production, which is relevant especially during a pandemic outbreak. In this review, we outline the current efforts to develop so-called “universal influenza vaccines”, describing antigens that may induce broadly protective immunity and novel vaccine production platforms that facilitate timely availability of vaccines. PMID:26343187
In response to the influenza vaccine shortage in the United States, the Connecticut Department of Public Health (DPH) operated a telephone hotline during October 22, 2004-January 15, 2005. The purpose of the hotline was to address questions from the public regarding the availability of influenza vaccine, reduce the number of telephone inquiries to physicians and local health departments (LHDs), and advise callers regarding which groups were most at risk and in need of influenza vaccination. Caller information was collected and shared daily with LHDs, which were encouraged to follow up with callers as their resources allowed. This report summarizes results of a retrospective survey of callers to the DPH influenza vaccine hotline during November 2004. The results indicated that vaccination coverage varied by age group and that persons receiving follow-up calls from LHDs were more likely to receive vaccination. State health departments might consider a hotline as a method for educating the public regarding influenza vaccination and a follow-up system as a means to improve vaccination coverage, especially among those at greatest risk.
Choi, Hyo-Jick; Yoo, Dae-Goon; Bondy, Brian J.; Quan, Fu-Shi; Compans, Richard W.; Kang, Sang-Moo; Prausnitz, Mark R.
A microneedle patch coated with vaccine simplifies vaccination by using a patch-based delivery method and targets vaccination to the skin for superior immunogenicity compared to intramuscular injection. Previous studies of microneedles have demonstrated effective vaccination using freshly prepared microneedles, but the issue of long-term vaccine stability has received only limited attention. Here, we studied the long-term stability of microneedles coated with whole inactivated influenza vaccine guided by the hypothesis that crystallization and phase separation of the microneedle coating matrix damages influenza vaccine coated onto microneedles. In vitro showed that the vaccine lost stability as measured by hemagglutination activity in proportion to the degree of coating matrix crystallization and phase separation. Transmission electron microscopy similarly showed damaged morphology of the inactivated virus vaccine associated with crystallization. In vivo assessment of immune response and protective efficacy in mice further showed reduced vaccine immunogenicity after influenza vaccination using microneedles with crystallized or phase-separated coatings. This work shows that crystallization and phase separation of the dried coating matrix are important factors affecting long-term stability of influenza vaccine-coated microneedles. PMID:22361098
Rodríguez-Fernández, R; Martínez-López, A B; Pérez-Moreno, J; González-Sánchez, M I; González-Martínez, F; Hernández-Sampelayo, T; Mejias, A
Influenza vaccination has been shown to be the most effective preventive strategy to reduce influenza-related morbidity and mortality in high-risk groups. Despite healthcare personnel (HCP) being considered part of such high-risk groups, their vaccination coverage is low in Europe. In January 2012, we distributed an 18-question survey regarding influenza vaccination to HCP at Gregorio Marañon Paediatric Hospital, in Madrid, Spain. After we documented that only ~30% of HCP were vaccinated an educational programme was implemented in October 2012 before the next influenza season. In January 2013, the same survey delivered again to all HCP documented a significant increase in vaccination rates (from 30% to 40%, P = 0·007) mainly among physicians and for patients' protection. In summary we found that a simple and inexpensive educational programme significantly improved the uptake of influenza vaccination in HCP in our centre. Nevertheless, vaccination rates remained low, and broader and updated campaigns are needed to overcome perception barriers.
Virk, Ramandeep Kaur; Gunalan, Vithiagaran; Tambyah, Paul Anantharajah
Influenza is a ubiquitous infection with a spectrum ranging from mild to severe. The mystery regarding such variability in the clinical spectrum has not been fully unravelled, although a role for the complex interplay among virus characteristics, host immune response and environmental factors has been suggested. Antivirals and current vaccines have a limited role in prophylaxis and treatment because they primarily target surface glycoproteins which undergo antigenic/genetic changes under host immune pressure. Targeting conserved internal proteins could lead the way to a universal vaccine which can be used against various types/subtypes. However, this is on the distant horizon, so in the meantime, developing improved vaccines should be given high priority. In this review, we discuss where the current influenza research stands in terms of vaccines, adjuvants, and how we can better predict the vaccine strains for upcoming influenza seasons by understanding complex phenomena which drive the continuous antigenic evolution.
Shahrabani, Shosh; Benzion, Uri
This study examines the impact of past experience with influenza and the influenza vaccine on four categories of the Health Belief Model: beliefs about susceptibility to contracting influenza, severity of illness, perceived benefits of the vaccine in preventing influenza, and perceived barriers to getting vaccinated. The study population comprised…
Ortiz de Lejarazu, Raúl; Tamames, Sonia
Seasonal influenza is an annual challenge for health-care systems, due to factors such as co-circulation of 2 influenza A subtypes jointly with 2 influenza B lineages; the antigenic drift of these virus, which eludes natural immunity, as well as immunity conferred by vaccination; together with influenza impact in terms of morbidity and mortality. Influenza vaccines have been available for more than 70 years and they have progressed in formulation, production and delivery route. Recommendations on vaccination are focused on those with a higher probability of severe disease, and have a progressively wider coverage, and classically based on inactivated vaccines, but with an increasing importance of attenuated live vaccines. More inactivated vaccines are becoming available, from adyuvanted and virosomal vaccines to intradermal delivery, cell-culture or quadrivalent. Overall vaccine effectiveness is about 65%, but varies depending on characteristics of vaccines, virus, population and the outcomes to be prevented, and ranges from less than 10% to almost 90%. Future challenges are formulations that confer more extensive and lasting protection, as well as increased vaccination coverage, especially in groups such as pregnant women and health-care professionals, as well as being extended to paediatrics.
Ropero-Álvarez, Alba María; El Omeiri, Nathalie; Kurtis, Hannah Jane; Danovaro-Holliday, M. Carolina; Ruiz-Matus, Cuauhtémoc
their campaigns to April-May following the review of national evidence. LAC countries have also established an official network dedicated to evaluating influenza vaccines effectiveness and impact. Conclusion: Following the A(H1N1)2009 influenza pandemic, countries of the Americas have continued their efforts to sustain or increase seasonal influenza vaccine uptake among high risk groups, especially among pregnant women. Countries also continued strengthening influenza surveillance, immunization platforms and information systems, indirectly improving preparedness for future pandemics. Influenza vaccination is particularly challenging compared to other vaccines included in EPI schedules, due to the need for annual, optimally timed vaccination, the wide spectrum of target groups, and the limitations of the available vaccines. Countries should continue to monitor influenza vaccination coverage, generate evidence for vaccination programs and implement social communication strategies addressing existing gaps. PMID:27196006
... HUMAN SERVICES Centers for Disease Control and Prevention Proposed Vaccine Information Materials for Influenza Vaccine AGENCY: Centers for Disease Control and Prevention (CDC), Department of Health and Human Services (HHS). ACTION: Notice with Comment Period. SUMMARY: Under the National Childhood Vaccine...
de Vries, Rory D.; Rimmelzwaan, Guus F.
ABSTRACT Antigenic drift of seasonal influenza viruses and the occasional introduction of influenza viruses of novel subtypes into the human population complicate the timely production of effective vaccines that antigenically match the virus strains that cause epidemic or pandemic outbreaks. The development of game-changing vaccines that induce broadly protective immunity against a wide variety of influenza viruses is an unmet need, in which recombinant viral vectors may provide. Use of viral vectors allows the delivery of any influenza virus antigen, or derivative thereof, to the immune system, resulting in the optimal induction of virus-specific B- and T-cell responses against this antigen of choice. This systematic review discusses results obtained with vectored influenza virus vaccines and advantages and disadvantages of the currently available viral vectors. PMID:27455345
Outin-Blenman, Sajata; Moen, Ann C.
During 2004–2009, the Centers for Disease Control and Prevention (CDC) partnered with 39 national governments to strengthen global influenza surveillance. Using World Health Organization data and program evaluation indicators collected by CDC in 2013, we retrospectively evaluated progress made 4–9 years after the start of influenza surveillance capacity strengthening in the countries. Our results showed substantial increases in laboratory and sentinel surveillance capacities, which are essential for knowing which influenza strains circulate globally, detecting emergence of novel influenza, identifying viruses for vaccine selection, and determining the epidemiology of respiratory illness. Twenty-eight of 35 countries responding to a 2013 questionnaire indicated that they have leveraged routine influenza surveillance platforms to detect other pathogens. This additional surveillance illustrates increased health-system strengthening. Furthermore, 34 countries reported an increased ability to use data in decision making; data-driven decisions are critical for improving local prevention and control of influenza around the world. PMID:27192395
Huang, Qiu Sue; Turner, Nikki; Baker, Michael G; Williamson, Deborah A; Wong, Conroy; Webby, Richard; Widdowson, Marc-Alain
The 2009 influenza A(H1N1)pdm09 pandemic highlighted the need for improved scientific knowledge to support better pandemic preparedness and seasonal influenza control. The Southern Hemisphere Influenza and Vaccine Effectiveness Research and Surveillance (SHIVERS) project, a 5-year (2012-2016) multiagency and multidisciplinary collaboration, aimed to measure disease burden, epidemiology, aetiology, risk factors, immunology, effectiveness of vaccination and other prevention strategies for influenza and other respiratory infectious diseases of public health importance. Two active, prospective, population-based surveillance systems were established for monitoring influenza and other respiratory pathogens among those hospitalized patients with acute respiratory illness and those enrolled patients seeking consultations at sentinel general practices. In 2015, a sero-epidemiological study will use a sample of patients from the same practices. These data will provide a full picture of the disease burden and risk factors from asymptomatic infections to severe hospitalized disease and deaths and related economic burden. The results during the first 2 years (2012-2013) provided scientific evidence to (a) support a change to NZ's vaccination policy for young children due to high influenza hospitalizations in these children; (b) contribute to the revision of the World Health Organization's case definition for severe acute respiratory illness for global influenza surveillance; and (c) contribute in part to vaccine strain selection using vaccine effectiveness assessment in the prevention of influenza-related consultations and hospitalizations. In summary, SHIVERS provides valuable international platforms for supporting seasonal influenza control and pandemic preparedness, and responding to other emerging/endemic respiratory-related infections.
Naval Health Research Center Mid-Season Influenza Vaccine Effectiveness Estimates for the 2013–2014 Influenza Season Angelia A. Cost...2000–2013 P A G E 1 5 Brief report: mid-season influenza vaccine effectiveness estimates for the 2013–2014 influenza season Angelia A. Cost, PhD...Mid-Season Influenza Vaccine Effectiveness Estimates for the 2013–2014 Influenza Season Angelia A
Huber, Victor C
Vaccination against influenza represents our most effective form of prevention. Historical approaches toward vaccine creation and production have yielded highly effective vaccines that are safe and immunogenic. Despite their effectiveness, these historical approaches do not allow for the incorporation of changes into the vaccine in a timely manner. In 2013, a recombinant protein-based vaccine that induces immunity toward the influenza virus hemagglutinin was approved for use in the USA. This vaccine represents the first approved vaccine formulation that does not require an influenza virus intermediate for production. This review presents a brief history of influenza vaccines, with insight into the potential future application of vaccines generated using recombinant technology.
Honda-Okubo, Yoshikazu; Saade, Fadi; Petrovsky, Nikolai
Advax™ adjuvant is derived from inulin, a natural plant-derived polysaccharide that when crystallized in the delta polymorphic form, becomes immunologically active. This study was performed to assess the ability of Advax™ adjuvant to enhance influenza vaccine immunogenicity and protection. Mice were immunized with influenza vaccine alone or combined with Advax™ adjuvant. Immuno-phenotyping of the anti-influenza response was performed including antibody isotypes, B-cell ELISPOT, CD4 and CD8 T-cell proliferation, influenza-stimulated cytokine secretion, DTH skin tests and challenge with live influenza virus. Advax™ adjuvant increased neutralizing antibody and memory B-cell responses to influenza. It similarly enhanced CD4 and CD8 T-cell proliferation and increased influenza-stimulated IL-2, IFN-γ, IL-5, IL-6, and GM-CSF responses. This translated into enhanced protection against mortality and morbidity in mice. Advax™ adjuvant provided significant antigen dose-sparing compared to influenza antigen alone. Protection could be transferred from mice that had received Advax™-adjuvanted vaccine to naïve mice by immune serum. Enhanced humoral and T-cell responses induced by Advax™-formulated vaccine were sustained 12 months post-immunization. Advax™ adjuvant had low reactogenicity and no adverse events were identified. This suggests Advax™ adjuvant could be a useful influenza vaccine adjuvant. PMID:22728225
Salleras, Luis; Navas, Encarna; Torner, Nuria; Prat, Andreu A.; Garrido, Patricio; Soldevila, Núria; Domínguez, Angela
The aim of this study was to systematically review published studies that evaluated the efficiency of inactivated influenza vaccination in preventing seasonal influenza in children. The vaccine evaluated was the influenza-inactivated vaccine in 10 studies and the virosomal inactivated vaccine in 3 studies. The results show that yearly vaccination of children with the inactivated influenza vaccine saves money from the societal and family perspectives but not from the public or private provider perspective. When vaccination does not save money, the cost-effectiveness ratios were very acceptable. It can be concluded, that inactivated influenza vaccination of children is a very efficient intervention. PMID:23295894
Wong, Terianne M; Ross, Ted M
Influenza vaccine design has changed considerably with advancements in bioinformatics and computational biology. Improved surveillance efforts provide up-to-date information about influenza sequence diversity and assist with monitoring the spread of epidemics and vaccine efficacy rates. The advent of next-generation sequencing, epitope scanning and high-throughput analysis all help decipher influenza-associated protein interactions as well as predict immune responsiveness based on host genetic diversity. Computational approaches are utilized in nearly all aspects of vaccine design, from modeling, compatibility predictions, and optimization of antigens in various platforms. This overview discusses how computational techniques strengthen vaccine efforts against highly diverse influenza species.
Iskander, John; Haber, Penina; Herrera, Guillermo
In the event that a vaccine is available during an influenza pandemic, vaccine safety monitoring will occur as part of comprehensive public health surveillance of the vaccination campaign. Though inactivated influenza vaccines have been widely used in the United States and much is known about their safety profile, attention will need to be paid to both common self-limited adverse reactions and rarer, more serious events that may or may not be causally related to vaccination. The primary surveillance systems used to generate and test hypotheses about vaccine safety concerns are the Vaccine Adverse Event Reporting System (VAERS) and the Vaccine Safety Datalink (VSD), respectively. Examples of recent use of these systems to investigate influenza vaccine safety and enhancements planned for use during a pandemic are presented. Ethical issues that will need to be addressed as part of an overall vaccine safety response include risk communication and injury compensation. Advance planning and the use of available technologic solutions are needed to respond to the scientific and logistic challenges involved in safely implementing mass vaccination during a pandemic. PMID:17132333
Zhang, Han; El Zowalaty, Mohamed E
Influenza is an illness of global public health concern. Influenza viruses have been responsible for several pandemics affecting humans. Current influenza vaccines have proved satisfactory safety; however, they have limitations and do not provide protection against unexpected emerging influenza virus strains. Therefore, there is an urgent need for alternative approaches to conventional influenza vaccines. The development of universal influenza vaccines will help alleviate the severity of influenza pandemics. Influenza DNA vaccines have been the subject of many studies over the past decades due to their ability to induce broad-based protective immune responses in various animal models. The present review highlights the recent advances in influenza DNA vaccine research and its potential as an affordable universal influenza vaccine.
de Perio, Marie A.; Wiegand, Douglas M.; Brueck, Scott E.
BACKGROUND Influenza can spread among students, teachers, and staff in school settings. Vaccination is the most effective method to prevent influenza. We determined 2012–2013 influenza vaccination coverage among school employees, assessed knowledge and attitudes regarding the vaccine, and determined factors associated with vaccine receipt. METHODS We surveyed 412 (49%) of 841 employees at 1 suburban Ohio school district in March 2013. The Web-based survey assessed personal and work characteristics, vaccine receipt, and knowledge and attitudes regarding the vaccine. RESULTS Overall, 238 (58%) respondents reported getting the 2012–2013 influenza vaccine. The most common reason for getting the vaccine was to protect oneself or one’s family (87%). Beliefs that the vaccine was not needed (32%) or that it was not effective (21%) were the most common reasons for not getting it. Factors independently associated with vaccine receipt were having positive attitudes toward the vaccine, feeling external pressure to get it, and feeling personal control over whether to get it. CONCLUSIONS Influenza vaccine coverage among school employees should be improved. Messages encouraging school employees to get the vaccine should address misconceptions about the vaccine. Employers should use methods to maximize employee vaccination as part of a comprehensive influenza prevention program. PMID:25117893
Araz, Ozgur M; Galvani, Alison; Meyers, Lauren A
Pandemic influenza is an international public health concern. In light of the persistent threat of H5N1 avian influenza and the recent pandemic of A/H1N1swine influenza outbreak, public health agencies around the globe are continuously revising their preparedness plans. The A/H1N1 pandemic of 2009 demonstrated that influenza activity and severity might vary considerably among age groups and locations, and the distribution of an effective influenza vaccine may be significantly delayed and staggered. Thus, pandemic influenza vaccine distribution policies should be tailored to the demographic and spatial structures of communities. Here, we introduce a bi-criteria decision-making framework for vaccine distribution policies that is based on a geospatial and demographically-structured model of pandemic influenza transmission within and between counties of Arizona in the Unites States. Based on data from the 2009-2010 H1N1 pandemic, the policy predicted to reduce overall attack rate most effectively is prioritizing counties expected to experience the latest epidemic waves (a policy that may be politically untenable). However, when we consider reductions in both the attack rate and the waiting period for those seeking vaccines, the widely adopted pro rata policy (distributing according to population size) is also predicted to be an effective strategy.
Coelingh, Kathleen L; Luke, Catherine J; Jin, Hong; Talaat, Kawsar R
Avian and animal influenza viruses can sporadically transmit to humans, causing outbreaks of varying severity. In some cases, further human-to-human virus transmission does not occur, and the outbreak in humans is limited. In other cases, sustained human-to-human transmission occurs, resulting in worldwide influenza pandemics. Preparation for future pandemics is an important global public health goal. A key objective of preparedness is to gain an understanding of how to design, test, and manufacture effective vaccines that could be stockpiled for use in a pandemic. This review summarizes results of an ongoing collaboration to produce, characterize, and clinically test a library of live attenuated influenza vaccine strains (based on Ann Arbor attenuated Type A strain) containing protective antigens from influenza viruses considered to be of high pandemic potential.
Park, Jae-Keun; Taubenberger, Jeffery K.
Influenza viruses are a significant public health threat, causing both annually circulating epidemics and unpredictable pandemics. Vaccination is the best means of control against individual cases of influenza and also for decreasing epidemic spread in the population. However, rapid influenza virus evolution requires continual reformulation of vaccines for annual influenza epidemics, and because pandemics cannot be accurately predicted, no current vaccine strategy can induce broad protection against all subtypes of influenza viruses. Recent work has suggested that such broadly protective, or “universal”, influenza virus vaccines might be achievable using vaccine strategies that target conserved B- and T-cell epitopes. PMID:26977452
Improving Rates of Influenza Vaccination Through Electronic Health Record Portal Messages, Interactive Voice Recognition Calls and Patient-Enabled Electronic Health Record Updates: Protocol for a Randomized Controlled Trial
Sreedhara, Meera; Goff, Sarah L; Fisher, Lloyd D; Preusse, Peggy; Jackson, Madeline; Sundaresan, Devi; Garber, Lawrence D; Mazor, Kathleen M
Background Clinical decision support (CDS), including computerized reminders for providers and patients, can improve health outcomes. CDS promoting influenza vaccination, delivered directly to patients via an electronic health record (EHR) patient portal and interactive voice recognition (IVR) calls, offers an innovative approach to improving patient care. Objective To test the effectiveness of an EHR patient portal and IVR outreach to improve rates of influenza vaccination in a large multispecialty group practice in central Massachusetts. Methods We describe a nonblinded, randomized controlled trial of EHR patient portal messages and IVR calls designed to promote influenza vaccination. In our preparatory phase, we conducted qualitative interviews with patients, providers, and staff to inform development of EHR portal messages with embedded questionnaires and IVR call scripts. We also provided practice-wide education on influenza vaccines to all physicians and staff members, including information on existing vaccine-specific EHR CDS. Outreach will target adult patients who remain unvaccinated for more than 2 months after the start of the influenza season. Using computer-generated randomization and a factorial design, we will assign 20,000 patients who are active users of electronic patient portals to one of the 4 study arms: (1) receipt of a portal message promoting influenza vaccines and offering online appointment scheduling; (2) receipt of an IVR call with similar content but without appointment facilitation; (3) both (1) and (2); or (4) neither (1) nor (2) (usual care). We will randomize patients without electronic portals (10,000 patients) to (1) receipt of IVR call or (2) usual care. Both portal messages and IVR calls promote influenza vaccine completion. Our primary outcome is percentage of eligible patients with influenza vaccines administered at our group practice during the 2014-15 influenza season. Both outreach methods also solicit patient self
Griffin, Marie R
Each year, an average of 5 to 10 percent of the U.S. population has symptomatic influenza illness, 226,000 persons are hospitalized and 24,000 die due to influenza-associated illness. Hospitalization rates are highest at the extremes of age, about one per 1,000 or higher in infants, persons age 65 and older and persons with chronic medical conditions. Ninety percent of deaths are in persons age 65 and older, but deaths also occur rarely in healthy children and young adults. Current influenza vaccines are moderately effective, with current evidence suggesting that they can prevent about half of influenza-associated symptomatic illness, outpatient visits, hospitalizations and deaths, with the evidence weaker for the most serious complications. Current licensed vaccines have mild immediate adverse effects and serious adverse effects are rare. Annual estimates of influenza vaccine effectiveness against the spectrum of clinical illness and in all age groups are needed to evaluate and support current vaccine policies and to help guide more effective vaccine development. Increased use of the current imperfect vaccines could prevent substantial morbidity and mortality in the U.S.
Suarez, David L
Vaccination for both low pathogenicity avian influenza and highly pathogenic avian influenza is commonly used by countries that have become endemic for avian influenza virus, but stamping-out policies are still common for countries with recently introduced disease. Stamping-out policies of euthanatizing infected and at-risk flocks has been an effective control tool, but it comes at a high social and economic cost. Efforts to identify alternative ways to respond to outbreaks without widespread stamping out has become a goal for organizations like the World Organisation for Animal Health. A major issue with vaccination for avian influenza is trade considerations because countries that vaccinate are often considered to be endemic for the disease and they typically lose their export markets. Primarily as a tool to promote trade, the concept of DIVA (differentiate infected from vaccinated animals) has been considered for avian influenza, but the goal for trade is to differentiate vaccinated and not-infected from vaccinated and infected animals because trading partners are unwilling to accept infected birds. Several different strategies have been investigated for a DIVA strategy, but each has advantages and disadvantages. A review of current knowledge on the research and implementation of the DIVA strategy will be discussed with possible ways to implement this strategy in the field. The increased desire for a workable DIVA strategy may lead to one of these ideas moving from the experimental to the practical.
Friede, M; Serdobova, I; Palkonyay, L; Kieny, M P
Increase of influenza vaccine production capacity in developing countries has been identified as an important element of global pandemic preparedness. Nevertheless, technology transfer for influenza vaccine production to developing country vaccine manufacturers has proven difficult because of lack of interested technology providers. As an alternative to an individual provider-recipient relationship, a technology and training platform (a "hub") for a generic non-proprietary process was established at a public sector European manufacturer's site. The conditions for setting up such a platform and the potential applicability of this model to other biologicals are discussed.
Davenport, F. M.
The history of the development of influenza virus vaccine is traced from its origin with experimental studies of influenza virus in ferrets and mice and the first trials in man. Knowledge of the basis of immunity to the viruses in experimental animals and in man has grown steadily over the years and has been essential to successful immunization. Virus variation affecting the surface antigens of the virus is seen as the principal obstacle to the application of vaccines in man. So significant are the changes occurring during antigenic drift that former concepts of a polyvalent vaccine cannot provide a solution of the problem of the composition of vaccines. Disrupted virus vaccines appear to provide the answer to the prevention of vaccine reactions. PMID:461277
Kattah, Nicole H.; Newell, Evan; Dekker, Cornelia L.; Davis, Mark M.; Utz, Paul J.
Background Existing methods to measure influenza vaccine immunogenicity prohibit detailed analysis of epitope determinants recognized by immunoglobulins. The development of highly multiplex proteomics platforms capable of capturing a high level of antibody binding information will enable researchers and clinicians to generate rapid and meaningful readouts of influenza-specific antibody reactivity. Methods We developed influenza hemagglutinin (HA) whole-protein and peptide microarrays and validated that the arrays allow detection of specific antibody reactivity across a broad dynamic range using commercially available antibodies targeted to linear and conformational HA epitopes. We derived serum from blood draws taken from 76 young and elderly subjects immediately before and 28±7 days post-vaccination with the 2008/2009 trivalent influenza vaccine and determined the antibody reactivity of these sera to influenza array antigens. Results Using linear regression and correcting for multiple hypothesis testing by the Benjamini and Hochberg method of permutations over 1000 resamplings, we identified antibody reactivity to influenza whole-protein and peptide array features that correlated significantly with age, H1N1, and B-strain post-vaccine titer as assessed through a standard microneutralization assay (p<0.05, q <0.2). Notably, we identified several peptide epitopes that were inversely correlated with regard to age and seasonal H1N1 and B-strain neutralization titer (p<0.05, q <0.2), implicating reactivity to these epitopes in age-related defects in response to H1N1 influenza. We also employed multivariate linear regression with cross-validation to build models based on age and pre-vaccine peptide reactivity that predicted vaccine-induced neutralization of seasonal H1N1 and H3N2 influenza strains with a high level of accuracy (84.7% and 74.0%, respectively). Conclusion Our methods provide powerful tools for rapid and accurate measurement of broad antibody-based immune
Kallon, Sanpha; Yu, Xingang
To determine the effect of astragalus and ginseng polysaccharides (APS, GPS) on immune response and improvement of H5N1 vaccine, 360-day-old broilers were randomly divided into 8 groups of 45 chicks, comprising APS groups (1–3); GPS groups (4–6); vaccine group (7); and blank control (8) (without polysaccharide and vaccine). From day 12 after hatch groups 1–3 were given APS and groups 4–6 with GPS both at 100, 200, and 400 (mg/kg), respectively. At day 15 after hatch, groups 1–7 were vaccinated with 0.3 mL H5N1 vaccine subcutaneously; daily weight gain (DWG) and serum Ig antibody (by HI-test) were measured on 3, 7, 14, and 28 days after vaccination. Serum antibody titers and expression of cytokines (IL-2, IL-10, I FN-γ, and TNF) were determined by ELISA and RT-PCR. Results revealed that all the polysaccharide groups were numerically increased in antibody levels and the expression of cytokines was significant (P < 0.05) in the APS and GPS groups compared to corresponding vaccine group and blank control. DWG was higher (P < 0.05) in 400 mg/kg APS groups than control groups. Thus oral supplements of GPS and APS have shown their potential in the improvement of immune response and could be used as adjuvant in a formulation of H5N1 vaccine. PMID:27597953
... Proclamation 8615--National Influenza Vaccination Week, 2010 #0; #0; #0; Presidential Documents #0; #0; #0;#0...;Title 3-- #0;The President ] Proclamation 8615 of December 7, 2010 National Influenza Vaccination Week... complications take American lives each year. During National Influenza Vaccination Week, we remind all...
Cooper, Curtis; Thorne, Anona
Clinical experience suggests Oculorespiratory Syndrome (ORS) following influenza vaccination is rare in HIV but this is not well evaluated. We assessed ORS incidence in a randomized influenza vaccine trial of HIV participants. The overall incidence was 0.8% suggesting that influenza vaccine ORS incidence is reduced in HIV.
Avian influenza (AI) vaccines have been developed and used to protect poultry and other birds in various countries of the world. Protection is principally mediated by an immune response to the subtype-specific hemagglutinin (HA) protein. AI vaccines prevent clinical signs of disease, death, egg pr...
Herl Jenlink, Carolyn; Kuehnert, Paul; Mazyck, Donna
The 2009 H1N1 influenza virus presented a major challenge to health departments, schools, and other community partners to effectively vaccinate large numbers of Americans, primarily children. The use of school-located vaccination (SLV) programs to address this challenge led health departments and schools to become creative in developing models for…
Current vaccines for influenza do not fully protect the aged against influenza infection. Wolfberry, or goji berry, has been shown to improve immune response including enhanced antibody production in response to vaccination in the aged; however, it is not known if this effect of wolfberry would tran...
Phippard, Alba E; Kimura, Akiko C; Lopez, Karla; Kriner, Paula
Hispanics are less likely to receive the influenza vaccine compared to other racial and ethnic groups in the US. Hispanic residents of the US-Mexico border region may have differing health beliefs and behaviors, and their cross-border mobility impacts disease control. To assess beliefs and behaviors regarding influenza prevention and control among border populations, surveys were conducted at border clinics. Of 197 respondents, 34 % reported conditions for which vaccination is indicated, and travel to Mexico was common. Few (35 %) believed influenza could make them 'very sick', and 76 % believed they should take antibiotics to treat influenza. Influenza vaccine awareness was high, and considered important, but only 36 % reported recent vaccination. The belief that influenza vaccination is 'very important' was strongly associated with recent vaccination; "Didn't think about it" was the most common reason for being un-vaccinated. Misconceptions about influenza risk, prevention and treatment were common in this Hispanic border population; improved educational efforts and reminder systems could impact vaccination behaviors.
Palache, Abraham; Oriol-Mathieu, Valerie; Fino, Mireli; Xydia-Charmanta, Margarita
Seasonal influenza is an important disease which results in 250,000-500,000 annual deaths worldwide. Global targets for vaccination coverage rates (VCRs) in high-risk groups are at least 75% in adults ≥65 years and increased coverage in other risk groups. The International Federation of Pharmaceutical Manufacturers and Associations Influenza Vaccine Supply (IFPMA IVS) International Task Force developed a survey methodology in 2008, to assess the global distribution of influenza vaccine doses as a proxy for VCRs. This paper updates the previous survey results on absolute numbers of influenza vaccine doses distributed between 2004 and 2013 inclusive, and dose distribution rates per 1000 population, and provides a qualitative assessment of the principal enablers and barriers to seasonal influenza vaccination. The two main findings from the quantitative portion of the survey are the continued negative trend for dose distribution in the EURO region and the perpetuation of appreciable differences in scale of dose distribution between WHO regions, with no observed convergence in the rates of doses distributed per 1000 population over time. The main findings from the qualitative portion of the survey were that actively managing the vaccination program in real-time and ensuring political commitment to vaccination are important enablers of vaccination, whereas insufficient access to vaccination and lack of political commitment to seasonal influenza vaccination programs are likely contributing to vaccination target failures. In all regions of the world, seasonal influenza vaccination is underutilized as a public health tool. The survey provides evidence of lost opportunity to protect populations against potentially serious influenza-associated disease. We call on the national and international public health communities to re-evaluate their political commitment to the prevention of the annual influenza disease burden and to develop a systematic approach to improve vaccine
Uhart, Mathieu; Bricout, Hélène; Clay, Emilie; Largeron, Nathalie
ABSTRACT Influenza B strains represent on average 23% of all circulating strains in Europe and when there is a vaccine mismatch on B strains, additional influenza-related hospitalizations and deaths as well as substantial additional costs are observed. The objective was to estimate the public health and economic impact of seasonal influenza vaccination with quadrivalent influenza vaccines (QIV) compared to trivalent influenza vaccines (TIV) in Europe (EU). Based on data from 5 EU countries (France, Germany, Italy, Spain and UK) during 10 influenza seasons from 2002 to 2013, epidemiological and associated economic outcomes were estimated for each season for the actual scenario where the TIV was used, and for a hypothetical scenario where QIV could have been used instead. By using QIV, this study estimated that for the 5 EU countries, an additional 1.03 million (327.9/100,000 inhabitants) influenza cases, 453,000 (143.9/100,000) general practitioners consultations, 672,000 (213.1/100,000) workdays lost, 24,000 (7.7/100,000) hospitalizations and 10,000 (3.1/100,000) deaths could have been avoided compared to the use of TIV over the 10-seasons-period. This study estimates that QIV can be of economic value since from a societal perspective 15 million Euros would have been saved on general practitioners consultations (14 million Euros from third-party payer perspective), 77 million on hospitalizations (74 million Euros from third-party payer perspective) and 150 million Euros on workdays lost, across the 5 EU countries. In conclusion, the present study estimates that, compared to TIV, QIV may result in a substantial decrease in epidemiological burden and in influenza-related costs. PMID:27166916
Bicho, Diana; Queiroz, João António; Tomaz, Cândida Teixeira
Current influenza vaccines have long been used to fight flu infectious; however, recent advances highlight the importance of produce new alternatives. Even though traditional influenza vaccines are safe and usually effective, they need to be uploaded every year to anticipate circulating flu viruses. This limitation together with the use of embryonated chicken eggs as the substrate for vaccine production, is time-consuming and could involve potential biohazards in growth of new virus strains. Plasmid DNA produced by prokaryote microorganisms and encoding foreign proteins had emerged as a promising therapeutic tool. This technology allows the expression of a gene of interest by eukaryotic cells in order to induce protective immune responses against the pathogen of interest. In this review, we discuss the strategies to choose the best DNA vaccine to be applied in the treatment and prevention of influenza. Specifically, we give an update of influenza DNA vaccines developments, all involved techniques, their main characteristics, applicability and technical features to obtain the best option against influenza infections.
... Influenza Vaccination Subgroup's Draft Report and Draft Recommendations for Achieving the Healthy People 2020 Annual Coverage Goals for Influenza Vaccination in Healthcare Personnel AGENCY: National Vaccine... of the National Vaccine Advisory Committee (NVAC), Healthcare Personnel Influenza...
Smith, D.J.; Ackley, D.H.; Forrest, S.; Perelson, A.S.
Although influenza vaccine efficacy is 70--90% in young healthy first-time vaccinees, the efficacy in repeat vaccinees has varied considerably. In some studies, vaccine efficacy in repeat vaccinees was higher than in first-time vaccinees, whereas in other studies vaccine efficacy in repeat vaccinees was significantly lower than in first-time vaccinees and sometimes no higher than in unvaccinated controls. It is known that the closeness of the antigenic match between the vaccine strain and the epidemic virus is important for vaccine effectiveness. In this study the authors show that the antigenic differences between a first vaccine strain and a second vaccine strain, and between the first vaccine strain and the epidemic strain, might account for the observed variation in attack rate among two-time vaccinees.
Stowe, Julia; Andrews, Nick; Wise, Lesley; Miller, Elizabeth
Concern about a possible increased risk of Bell's palsy after parenteral inactivated influenza vaccine was raised following the publication in 2004 of a Swiss study in which there was an increased risk following the nasal inactivated formulation of the vaccine. When data from passive reporting systems in the United States and the United Kingdom were examined there was some evidence of increased reporting following the parenteral vaccine. A large population based study using the General Practice Research Database (GPRD) was therefore performed to test the hypothesis that there was an increased risk of Bell's palsy in the three months following parenteral inactivated influenza vaccine. The risk was also assessed for the same period following pneumococcal vaccine and was stratified into three age groups (<45, 45-64 and 65+ years). Relative incidence (RI) estimates were calculated using the self-controlled case-series method and showed no evidence of an increased risk in the three months following parenteral inactivated influenza vaccine RI 0.92 (95% confidence interval 0.78-1.08). There was also no evidence of an increased risk in any age group or following pneumococcal vaccine. A significant increase was seen on the day of vaccination (day 0) probably due to opportunistic recording of cases.
The emergence and spread of highly pathogenic avian influenza (H5N1) viruses among poultry in Asia, the Middle East, and Africa have fueled concerns of a possible human pandemic, and spurred efforts towards developing vaccines against H5N1 influenza viruses, as well as improving vaccine production methods. In recent years, promising experimental reverse genetics-derived H5N1 live attenuated vaccines have been generated and characterized, including vaccines that are attenuated through temperature-sensitive mutation, modulation of the interferon antagonist protein, or disruption of the M2 protein. Live attenuated influenza virus vaccines based on each of these modalities have conferred protection against homologous and heterologous challenge in animal models of influenza virus infection. Alternative vaccine strategies that do not require the use of live virus, such as virus-like particle (VLP) and DNA-based vaccines, have also been vigorously pursued in recent years. Studies have demonstrated that influenza VLP vaccination can confer homologous and heterologous protection from lethal challenge in a mouse model of infection. There have also been improvements in the formulation and production of vaccines following concerns over the threat of H5N1 influenza viruses. The use of novel substrates for the growth of vaccine virus stocks has been intensively researched in recent years, and several candidate cell culture-based systems for vaccine amplification have emerged, including production systems based on Madin-Darby canine kidney, Vero, and PerC6 cell lines. Such systems promise increased scalability of product, and reduced reliance on embryonated chicken eggs as a growth substrate. Studies into the use of adjuvants have shown that oil-in-water-based adjuvants can improve the immunogenicity of inactivated influenza vaccines and conserve antigen in such formulations. Finally, efforts to develop more broadly cross-protective immunization strategies through the inclusion
Lind, Candace; Russell, Margaret L.; MacDonald, Judy; Collins, Ramona; Frank, Christine J.; Davis, Amy E.
Background School-age children are important drivers of annual influenza epidemics yet influenza vaccination coverage of this population is low despite universal publicly funded influenza vaccination in Alberta, Canada. Immunizing children at school may potentially increase vaccine uptake. As parents are a key stakeholder group for such a program, it is important to consider their concerns. Purpose We explored parents’ perspectives on the acceptability of adding an annual influenza immunization to the immunization program that is currently delivered in Alberta schools, and obtained suggestions for structuring such a program. Participants Forty-eight parents of children aged 5-18 years participated in 9 focus groups. Participants lived in urban areas of the Alberta Health Services Calgary Zone. Findings Three major themes emerged: Advantages of school-based influenza vaccination (SBIV), Disadvantages of SBIV, and Implications for program design & delivery. Advantages were perceived to occur for different populations: children (e.g. emotional support), families (e.g. convenience), the community (e.g. benefits for school and multicultural communities), the health sector (e.g. reductions in costs due to burden of illness) and to society at large (e.g. indirect conduit of information about health services, building structure for pandemic preparedness, building healthy lifestyles). Disadvantages, however, might also occur for children (e.g. older children less likely to be immunized), families (e.g. communication challenges, perceived loss of parental control over information, choices and decisions) and the education sector (loss of instructional time). Nine second-level themes emerged within the major theme of Implications for program design & delivery: program goals/objectives, consent process, stakeholder consultation, age-appropriate program, education, communication, logistics, immunizing agent, and clinic process. Conclusions Parents perceived advantages and
Rajput, Zahid Iqbal; Xiao, Chen-wen; Hu, Song-hua; Arijo, Abdullah G.; Soomro, Noor Mohammad
Seeds of a Chinese traditional medicine plant, Cochinchina momordica were used in the present study for the improvement of influenza vaccine (H5N1) in chicken. Crude extraction from Cochinchina momordica seed (ECMS) was obtained by ethanol extraction method. In experiment No. 1, two weeks old chickens were immunized with influenza vaccine (H5N1) alone or combined with ECMS (5, 10, 20, 40 and 80 μg/dose). Serum IgG antibody levels (by ELISA) as well as effects on daily weight gain were measured on 0, 7, 14 and 28th day after immunization. Results revealed that all ECMS groups numerically increased the antibody levels while 10 and 20 μg/dose groups significantly (P<0.05) enhanced total IgG antibody on day 28, when compared with control. Average daily weight gain was also significantly higher in 20 μg/dose ECMS group. Adjuvant effect was also confirmed in experiment No. 2 when chickens were immunized with 20 μg/dose ECMS and antibody titer was measured through hemagglutination inhibition (HI). It is concluded that ECMS has potential to improve the immune responses and deserve further study as an adjuvant. PMID:17542061
Ping, Jihui; Lopes, Tiago J.S.; Nidom, Chairul A.; Ghedin, Elodie; Macken, Catherine A.; Fitch, Adam; Imai, Masaki; Maher, Eileen A.; Neumann, Gabriele; Kawaoka, Yoshihiro
Vaccination is one of the most cost-effective ways to prevent infection. Influenza vaccines propagated in cultured cells are approved for use in humans, but their yields are often suboptimal. Here, we screened A/Puerto Rico/8/34 (PR8) virus mutant libraries to develop vaccine backbones (defined here as the six viral RNA segments not encoding haemagglutinin and neuraminidase) that support high yield in cell culture. We also tested mutations in the coding and regulatory regions of the virus, and chimeric haemagglutinin and neuraminidase genes. A combination of high-yield mutations from these screens led to a PR8 backbone that improved the titres of H1N1, H3N2, H5N1 and H7N9 vaccine viruses in African green monkey kidney and Madin–Darby canine kidney cells. This PR8 backbone also improves titres in embryonated chicken eggs, a common propagation system for influenza viruses. This PR8 vaccine backbone thus represents an advance in seasonal and pandemic influenza vaccine development. PMID:26334134
Taylor, Eric G.; Atkins, Katherine E.; Chapman, Gretchen B.; Galvani, Alison P.
Objective Americans do not vaccinate nearly enough against Influenza (flu) infection, despite severe health and economic burden of influenza. Younger people are disproportionately responsible for transmission, but do not suffer severely from the flu. Thus, to achieve herd immunity, prosocial motivation needs to be a partial driver of vaccination decisions. Past research has not established the causal role of prosociality in flu vaccination, and the current research evaluates such causal relationship by experimentally eliciting prosociality through messages about flu victims. Methods In an experimental study, we described potential flu victims who would suffer from the decision of others to not vaccinate to 3952 Internet participants across eight countries. We measured sympathy, general prosociality, and vaccination intentions. The study included two identifiable victim conditions (one with an elderly victim and another with a young victim), an unidentified victim condition, and a no message condition. Results We found that any of the three messages increased flu vaccination intentions. Moreover, this effect was mediated by enhanced prosocial motives, and was stronger among people who were historical non-vaccinators. In addition, younger victim elicited greater sympathy, and describing identifiable victims increased general sympathy and prosocial motives. Conclusions These findings provide direct experimental evidence on the causal role of prosocial motives in flu vaccination, by showing that people can be prompted to vaccinate for the sake of benefiting others. PMID:27459237
Stowers, Chanelle; Healey, Loretta; O'Connor, Catherine C
A trial of using Short Message Service (SMS) broadcasting at a metropolitan sexual health clinic in 2013 to promote the awareness and uptake of influenza vaccinations in HIV-positive patients resulted in a significant increase in the number of patients contacted (35% vs 81% P<0.0001) and vaccinated by the clinic (26% vs 47% P<0.001) compared with 2012, when individual telephone calls were made to patients. Additional benefits were less staff time used promoting influenza vaccination and the resultant lower staff cost. SMS broadcasting is an efficient and inexpensive method of communicating health messages to large numbers of patients.
Plasai, Valaikanya; Lertmaharit, Somrat; Viputsiri, Ong-Arj; Pongpanich, Sathirakorn; Panichpathompong, Usa; Tarnmaneewongse, Veerachai; Baron-Papillon, Florence; Cheunkitmongkol, Sunate
This study aimed to determine the effectiveness of influenza vaccinations among the elderly in Bangkok in reducing influenza-like illness (ILI) and influenza-related complications. Using a non-randomized, controlled, prospective methodology, healthy, active people aged 60 years or more, living in the Bangkok Metropolitan Administration (BMA) area, were studied. The two study cohorts comprised 519 persons in the vaccinated group and 520 in the non-vaccinated group. The outcome under study was influenza-like illness (ILI), as reported by the study volunteers. The two groups were comparable for most socio-demographic characteristics, except for gender, level of education, marital status, and smoking habit. The age range was 60-88 years (mean: 68 years). Females outnumbered males in both groups, with ratio of female to male of 2.6:1 and 1.9:1 in the vaccinated and non-vaccinated groups, respectively. The top three co-morbidities among these groups were hypertension, diabetes mellitus, and heart disease, in that order. Only 1% of the volunteers reported lung disease as co-morbidity. During the 12-month study period, a total of 107 volunteers reported ILI in both groups, with 38 persons in the vaccinated group and 69 persons in the non-vaccinated group. There were 46 ILI episodes in the vaccinated group, and 86 in the non-vaccinated group, for a total of 132 episodes. The incidence rates rates of influenza in this population, therefore, were 8.9% for the vaccinated and 16.9% for the non-vaccinated groups; with a reduction in the rate of reported ILI and doctor visits of 8%. Vaccine effectiveness was rated at 47.6%, crude risk ratio at 1.9 (1.33-2.75), and adjusted risk ratio at 1.92 (95% CI: 1.25-2.95), after adjustment for gender, marital status, education, and smoking habit. No complications due to ILI were observed in this population during the study period. Hospitalizations during this period were due to non-ILI related causes, such as cancer and accident.
Ko, Hyun Sun; Jo, Yun Seong; Kim, Yeun Hee; Park, Yong-Gyu; Moon, Hee Bong; Lee, Young
Objective The aims of the present study were to investigate the women's perspective on influenza infection and vaccination and to evaluate how they influence vaccine acceptability, in Korean women of childbearing age. Methods This was a prospective study by random survey of women of childbearing age (20 to 45 years). They were asked to complete a questionnaire assessing their knowledge, attitudes and acceptability of influenza vaccination before and during pregnancy. This study utilized data from the Korea National Health and Nutrition Examination Survey (KNHANES) between 2008 and 2012, to analyze the recent influenza vaccination trends. Results According to KNHANES (2008-2012), influenza vaccination rates in women of childbearing age have increased up to 26.4%, after 2009. The questionnaire was completed by 308 women. Vaccination rate during pregnancy or planning a pregnancy was 38.6%. The immunization rate increased significantly with the mean number of correct answers (P<0.001). Women who received influenza vaccination were more likely to be previously informed of the recommendations concerning the influenza vaccination before or during pregnancy, received the influenza vaccination in the past, and of the opinion that influenza vaccination is not dangerous during pregnancy, with odds ratios of 14.6 (95% confidence interval [CI], 6.44 to 33.33; P<0.0001), 3.6 (95% CI, 1.84 to 6.97; P=0.0002) and 2.7 (95% CI, 1.34 to 5.47; P=0.0057). Conclusion Influenza vaccination rate in women of childbearing age has increased in this study and national data. More information and recommendation by healthcare workers, especially obstetricians, including safety of vaccination, might be critical for improving vaccination rate in women of childbearing age. PMID:25798420
Telford, Rosie; Rogers, Anne
Influenza and its related illnesses remain a major cause of preventable morbidity and mortality in the elderly worldwide. The current influenza vaccine campaign in the UK is only a partial success despite annual costly publicity campaigns. The aim of this study was to explore the influences on decision making by elderly people for influenza vaccine uptake. Twenty patients age 75 years and over were purposively selected from those eligible for influenza vaccination in an inner city general practice in England. In-depth qualitative interviews were conducted with 10 patients who accepted and 10 who refused the vaccine. Those interviewed were concerned about maintaining their health, and had a good understanding of influenza, its transmission and prevention. The decision whether to accept or refuse the influenza vaccination was influenced by trust or mistrust of modern medicine, prior experience of vaccination and perceived risk from influenza. Newly acquired lay experience and personal perceived risk from influenza seemed to be more important catalysts for the change in vaccination uptake than professional recommendation or advertising by official government health agencies. In order to improve uptake rates, the official message promoting vaccine uptake needs to take more account of lay knowledge and the subjective assessment of risk.
Yu, J; Shi, F S; Hu, S
Our previous investigation demonstrated that ginseng stem-leaf saponins (GSLS) derived from the stems and leaves of Panax ginseng C.A. Meyer promoted humoral and gut mucosal immunity in chickens vaccinated with live infectious bursa disease vaccine. The present study was designed to evaluate the effect of GSLS on the immune response to a bivalent inactive vaccine of Newcastle disease (ND) and avian influenza (AI) in chickens immunosuppressed by cyclophosphamide (Cy). One hundred and sixty-eight specific-pathogen-free (SPF) chickens were randomly divided into 7 groups, each containing 24 birds. Chickens in groups 3-7 received intramuscular injection of Cy at 100mg/kg BW for 3 days to induce immunosuppression. Groups 1 and 2 were injected with saline solution in the same way as groups 3-7. Following injection of Cy, groups 4-7 were orally administrated GSLS (2.5, 5 and 10mg/kg BW) or astragalus polysaccharide (APS) (200mg/L) in drinking water for 7 days; groups 1-3 were not medicated and served as control birds. After administration of GSLS or APS, groups 2-7 were subcutaneously injected with a bivalent inactive vaccine of ND and AI. After that, serum was sampled for detecting antibody titers by HI, spleen was collected for lymphocyte proliferation assay, and duodenum tissues were collected for measurement of IgA-secreting (IgA+) cells and intestinal intraepithelial lymphocytes (iIELs). The results showed that injection of Cy significantly suppressed immunity in chickens; oral administration of GSLS before immunization recovered splenocyte proliferation induced by ConA and LPS, and the numbers of IgA+ cells and iIELs as well as the specific antibody response to a bivalent inactive vaccine of ND and AIin immunosuppressed chickens treated with Cy. Therefore, GSLS may be the potential agent to improve vaccination in immunosuppressed chickens.
MedImmune Vaccines (formerly Aviron) has developed a cold-adapted live influenza virus vaccine [FluMist] that can be administered by nasal spray. FluMist is the first live virus influenza vaccine and also the first nasally administered vaccine to be marketed in the US. The vaccine will be formulated to contain live attenuated (att) influenza virus reassortants of the strains recommended by the US Public Health Service for each 'flu season. The vaccine is termed cold-adapted (ca) because the virus has been adapted to replicate efficiently at 25 degrees C in the nasal passages, which are below normal body temperature. The strains used in the seasonal vaccine will also be made temperature sensitive (ts) so that their replication is restricted at 37 degrees C (Type B strains) and 39 degrees C (Type A strains). The combined effect of the antigenic properties and the att, ca and ts phenotypes of the influenza strains contained in the vaccine enables the viruses to replicate in the nasopharynx to produce protective immunity. The original formulation of FluMist requires freezer storage throughout distribution. Because many international markets do not have distribution channels well suited to the sale of frozen vaccines, Wyeth and MedImmune are collaborating to develop a second generation, refrigerator-stable, liquid trivalent cold-adapted influenza vaccine (CAIV-T), which is in phase III trials. Initially, the frozen formulation will only be available in the US. For the 2003-2004 season, FluMist will contain A/New Caledonia/20/99 (H1N1), A/Panama/2007/99 (H3N2) (A/Moscow/10/99-like) and B/Hong Kong/330/2001. Aviron was acquired by MedImmune on 15 January 2002. Aviron is now a wholly-owned subsidiary of MedImmune and is called MedImmune Vaccines. Aviron acquired FluMist in March 1995 through a Co-operative Research and Development Agreement (CRADA) with the US NIAID, and a licensing agreement with the University of Michigan, Ann Arbor, USA. In June 2000, the CRADA was
Buckland, Barry C
The development and manufacture of an Influenza vaccine is unlike any other product in the Vaccine industry because of the need to change composition on a yearly basis. The poor efficacy of Influenza vaccines over the past 2 y in the Northern Hemisphere invites questions on how the vaccines are manufactured and how change in vaccine composition is controlled. The opinion expressed in this commentary is that the risk of not making the correct HA protein is increased by the need to adapt the new seasonal virus for good propagation in embryonated chicken eggs. This adaptation is required because not enough doses can be made in time for the new 'flu season unless productivity is reasonable. This problem is not necessarily solved by going to a cell culture host for virus propagation and that may explain why this more advanced technology approach is not more widely used. A vaccine based on hemagglutinin (HA) protein that does not involve Influenza virus propagation (such as Flublok®) side steps this particular problem. The exact HA sequence can be used as is in the virus. The technology can be run at large scale, already at 2 × 21,000L in Japan, in contrast to eggs where scale-up is by multiplication; the HA product is highly purified and made consistently in the form of rosettes. PMID:25844949
reported reason for non-vaccination was ‘I don’t think I am very likely to catch the flu’ (49.3%). Conclusions Within the general population of Beijing the vaccination coverage rates were relatively low and did not change significantly after the influenza pandemic. The perception of not expecting to contract influenza was the predominant barrier to influenza vaccination. Further measures are needed to improve influenza vaccination coverage. PMID:23835253
Wahid, Rahnuma; Holt, Renee; Hjorth, Richard; Berlanda Scorza, Francesco
With the support of the Biomedical Advanced Research and Development Authority (BARDA) of the US Department of Health and Human Services, PATH has contributed to the World Health Organization's (WHO's) Global Action Plan for Influenza Vaccines (GAP) by providing technical and clinical assistance to several developing country vaccine manufacturers (DCVMs). GAP builds regionally based independent and sustainable influenza vaccine production capacity to mitigate the overall global shortage of influenza vaccines. The program also ensures adequate influenza vaccine manufacturing capacity in the event of an influenza pandemic. Since 2009, PATH has worked closely with two DCVMs in Vietnam: the Institute of Vaccines and Medical Biologicals (IVAC) and VABIOTECH. Beginning in 2013, PATH also began working with Torlak Institute in Serbia; Instituto Butantan in Brazil; Serum Institute of India Private Ltd. in India; and Changchun BCHT Biotechnology Co. (BCHT) in China. The DCVMs supported under the GAP program all had existing influenza vaccine manufacturing capability and required technical support from PATH to improve vaccine yield, process efficiency, and product formulation. PATH has provided customized technical support for the manufacturing process to each DCVM based on their respective requirements. Additionally, PATH, working with BARDA and WHO, supported several DCVMs in the clinical development of influenza vaccine candidates progressing toward national licensure or WHO prequalification. As a result of the activities outlined in this review, several companies were able to make excellent progress in developing state-of-the-art manufacturing processes and completing early phase clinical trials. Licensure trials are currently ongoing or planned for several DCVMs.
Prior to 2003, vaccines against avian influenza (AI) had limited, individual country or regional use in poultry. In late 2003, H5N1 high pathogenicity (HP) AI spread from China to multiple Southeast Asian countries, and to Europe during 2005 and Africa during 2006, challenging governments and all p...
Nakayama, Tetsuo; Kumagai, Takuji; Nishimura, Naoko; Ozaki, Takao; Okafuji, Teruo; Suzuki, Eitaro; Miyata, Akiko; Okada, Kenji; Ihara, Toshiaki
Although anaphylaxis is an extremely rare vaccine-associated adverse event, it occurred in young children following administration of the 2011/12 seasonal split influenza vaccine, which contained 2-phenoxyethanol as the preservative. These children had high levels of IgE antibodies against influenza vaccine components. We herein investigated why these children were sensitized. One hundred and seventeen series of serum samples were obtained immediately before, and one month after the first and second immunizations with the HA split vaccine of 2011/12. Forty-two sequential serum samples were collected in the acute and convalescent phases (2 and 4 weeks) after natural infection with H1N1 Pdm in 2009. IgE antibodies developed following the vaccination of young children with seasonal split vaccines, whereas no significant IgE response was observed following natural infection with H1N1 Pdm 2009. The prevalence of IgE antibodies was not influenced by outbreaks of H1N1 Pdm. Repeated immunization with the HA split vaccine induced IgE sensitization against the influenza vaccine irrespective of the H1N1, H3N2, or B influenza subtypes. The reasons why anaphylaxis only occurred in recipients of the influenza vaccine containing 2-phenoxyethanol are still being investigated, and the size distribution of antigen particles may have shifted to a slightly larger size. Since the fundamental reason was IgE sensitization, current split formulation for the seasonal influenza vaccine needs to be reconsidered to prevent the induction of IgE sensitization.
controlled studies. Vaccine 2012; 30:886–92. 11. Piedra PA, Gaglani MJ, Kozinetz CA, et al. Trivalent live attenuated intranasal influenza vaccine...120:e553–64. 12. Halloran ME, Piedra PA, Longini IM Jr, et al. Efficacy of trivalent, cold-adapted, influenza virus vaccine against influenza A (Fujian
Barman, Subrata; Krylov, Petr S; Turner, Jasmine C; Franks, John; Webster, Robert G; Husain, Matloob; Webby, Richard J
In 2013, a novel avian-origin H7N9 influenza A virus causing severe lower respiratory tract disease in humans emerged in China, with continued sporadic cases. An effective vaccine is needed for this virus in case it acquires transmissibility among humans; however, PR8-based A/Anhui/1/2013 (Anhui/1, H7N9), a WHO-recommended H7N9 candidate vaccine virus (CVV) for vaccine production, does not replicate well in chicken eggs, posing an obstacle to egg-based vaccine production. To address this issue, we explored the possibility that PR8's hemagglutinin (HA) and neuraminidase (NA) packaging signals mediate improvement of Anhui/1 CVV yield in eggs. We constructed chimeric HA and NA genes having the coding region of Anhui/1 HA and NA flanked by the 5' and 3' packaging signals of PR8's HA and NA, respectively. The growth of CVVs containing the chimeric HA was not affected, but that of those containing the chimeric NA gene grew in embryonated chicken eggs with a more than 2-fold higher titer than that of WT CVV. Upon 6 passages in eggs further yield increase was achieved although this was not associated with any changes in the chimeric NA gene. The HA of the passaged CVV, did, however, exhibit egg-adaptive mutations and one of them (HA-G218E) improved CVV growth in eggs without significantly changing antigenicity. The HA-G218E substitution and a chimeric NA, thus, combine to provide an Anhui/1 CVV with properties more favorable for vaccine manufacture.
Nannei, Claudia; Chadwick, Christopher; Fatima, Hiba; Goldin, Shoshanna; Grubo, Myriam; Ganim, Alexandra
Through its Global Action Plan for Influenza Vaccines (GAP), the World Health Organization (WHO) in collaboration with the United States Department of Health and Human Services has produced a checklist to support policy-makers and influenza vaccine manufacturers in identifying key technological, political, financial, and logistical issues affecting the sustainability of influenza vaccine production. This checklist highlights actions in five key areas that are beneficial for establishing successful local vaccine manufacturing. These five areas comprise: (1) the policy environment and health-care systems; (2) surveillance systems and influenza evidence; (3) product development and manufacturing; (4) product approval and regulation; and (5) communication to support influenza vaccination. Incorporating the checklist into national vaccine production programmes has identified the policy gaps and next steps for countries involved in GAP's Technology Transfer Initiative. Lessons learnt from country experiences provide context and insight that complement the checklist's goal of simplifying the complexities of influenza prevention, preparedness, and vaccine manufacturing.
Ellis, T M; Sims, L D; Wong, H K H; Wong, C W; Dyrting, K C; Chow, K W; Leung, C; Peiris, J S M
Outbreaks of H5N1 highly pathogenic avian influenza (HPAI) that occurred in Hong Kong up until February/March 2002 were controlled by stamping out. With endemic presence of the virus in the region and large daily importation of poultry to Hong Kong, the Administration considered that further risk management measures, in addition to improved biosecurity and enhanced surveillance, were necessary to prevent outbreaks. Vaccination using a killed H5N2 vaccine was evaluated over a 12-month period in the district with the last HPAI cases in the early 2002 outbreak. The vaccination trial showed that farmer-administered killed H5N2 vaccine produced suitable flock antibody responses; vaccinated birds were protected against H5N1 HPAI virus challenge and excreted significantly less H5N1 virus; and vaccination was able to control virus excretion in flocks during field outbreaks. Universal vaccination of local chicken farms was introduced in June 2003 and by the end of 2003 all chickens entering the live poultry markets in Hong Kong were vaccinated by killed H5N2 vaccine. In addition to vaccination, an enhanced biosecurity programme on farms and in live poultry markets and a comprehensive surveillance programme in poultry, wild birds, recreation park birds and pet birds were in place. Vaccination use and performance is closely monitored. This programme was successful in protecting local farms and live poultry markets from H5N1 outbreaks during the regional H5N1 outbreaks in 2004.
Zarnitsyn, Vladimir G.; Sullivan, Sean P.; Compans, Richard W.; Prausnitz, Mark R.; Skountzou, Ioanna
Background Influenza is a contagious disease caused by a pathogenic virus, with outbreaks all over the world and thousands of hospitalizations and deaths every year. Due to virus antigenic drift and short-lived immune responses, annual vaccination is required. However, vaccine coverage is incomplete, and improvement in immunization is needed. The objective of this study is to investigate a novel method for transdermal delivery using metal microneedle arrays (MN) coated with inactivated influenza virus to determine whether this route is a simpler and safer approach than the conventional immunization, capable to induce robust immune responses and confer protection against lethal virus challenge. Methodology/Principal Findings Inactivated A/Aichi/2/68 (H3N2) influenza virus was coated on metal microneedle arrays and applied to mice as a vaccine in the caudal dorsal skin area. Substantial antibody titers with hemagglutination inhibition activity were detected in sera collected two and four weeks after a single vaccine dose. Challenge studies in mice with 5×LD50 of mouse adapted Aichi virus demonstrated complete protection. Microneedle vaccination induced a broad spectrum of immune responses including CD4+ and CD8+ responses in the spleen and draining lymph node, a high frequency of antigen-secreting cells in the lung and induction of virus-specific memory B-cells. In addition, the use of MN showed a dose-sparing effect and a strong Th2 bias when compared to an intramuscular (IM) reference immunization. Conclusions/Significance The present results show that delivery of inactivated influenza virus through the skin using metal microneedle arrays induced strong humoral and cellular immune responses capable of conferring protection against virus challenge as efficiently as intramuscular immunization, which is the standard vaccination route. In view of the convenience of delivery and the potential for self-administration, vaccine-coated metal microneedles may provide a
Sullivan, Shannon M; Pierrynowski-Gallant, Donna; Chambers, Larry; O'Connor, Annette; Bowman, Sherry; McNeil, Shelly; Strang, Robert; Knoefel, Frank
The purpose of this study was to determine whether direct nursing care providers have decisional conflict about receiving influenza vaccinations and characteristics associated with decisional conflict. The researchers used a self-administered questionnaire mailed to direct nursing care providers in two long-term-care organizations. Most direct nursing care providers in both organizations (80% and 93%, respectively) intended to get the influenza vaccine. Unregulated direct nursing care providers had more decisional conflict than regulated providers, especially related to feeling uninformed about the pros and cons of influenza vaccination. Unclear valuing of the pros and cons of influenza vaccination was related to the age of the direct care providers in both organizations. Decisional conflict and influenza vaccination practices may be determined, in part, by age and by the culture of a health care organization. A decision aid to improve knowledge and clarify values may improve decision quality and increase influenza vaccination rates.
Banach, David B; Ornstein, Katherine; Factor, Stephanie H; Soriano, Theresa A
Seasonal influenza vaccination is recommended for all persons aged ≥50 years to reduce influenza related morbidity and mortality, but vaccination coverage among community-dwelling elderly remains low. Homebound elderly receiving home-based primary care (HBPC) have fewer barriers to vaccination than other community-dwelling elderly. The Mount Sinai Visiting Doctors (MSVD) program provides HBPC to homebound elderly in New York City. This study assessed seasonal influenza vaccination coverage within an urban HBPC program and identified factors associated with vaccine refusal. A cross-sectional analysis of data from the 2008-2009 influenza season was completed and influenza vaccination coverage was assessed. The association between social, demographic and health-related characteristics and vaccine refusal was evaluated using bivariate analysis and multivariable logistic regression. Of 689 people aged >65 eligible for influenza vaccination, 578 (84%) accepted and 111 (16%) refused vaccination. In multivariable analysis, vaccine refusal was positively associated with female gender (adjusted odds ratio [AOR] = 1.85, 95% confidence interval [CI] 1.02, 3.35), black race (AOR = 2.04, 95% CI 1.28, 3.25), and living alone (AOR = 1.71, 95% CI 1.10, 2.67), and negatively associated with dementia (AOR = 0.59, 95% CI 0.37, 0.91). Seasonal influenza vaccine coverage in the MSVD program was high compared to nursing home and community-dwelling elderly. Offering patients vaccination at home without additional expense will likely improve vaccine coverage among urban homebound elderly. Understanding why vaccine refusal rates are higher among females, black patients, and those living alone should guide interventions to increase vaccine acceptance among this population.
Nogales, Aitor; Martínez-Sobrido, Luis
Influenza viruses cause annual seasonal epidemics and occasional pandemics of human respiratory disease. Influenza virus infections represent a serious public health and economic problem, which are most effectively prevented through vaccination. However, influenza viruses undergo continual antigenic variation, which requires either the annual reformulation of seasonal influenza vaccines or the rapid generation of vaccines against potential pandemic virus strains. The segmented nature of influenza virus allows for the reassortment between two or more viruses within a co-infected cell, and this characteristic has also been harnessed in the laboratory to generate reassortant viruses for their use as either inactivated or live-attenuated influenza vaccines. With the implementation of plasmid-based reverse genetics techniques, it is now possible to engineer recombinant influenza viruses entirely from full-length complementary DNA copies of the viral genome by transfection of susceptible cells. These reverse genetics systems have provided investigators with novel and powerful approaches to answer important questions about the biology of influenza viruses, including the function of viral proteins, their interaction with cellular host factors and the mechanisms of influenza virus transmission and pathogenesis. In addition, reverse genetics techniques have allowed the generation of recombinant influenza viruses, providing a powerful technology to develop both inactivated and live-attenuated influenza vaccines. In this review, we will summarize the current knowledge of state-of-the-art, plasmid-based, influenza reverse genetics approaches and their implementation to provide rapid, convenient, safe and more effective influenza inactivated or live-attenuated vaccines. PMID:28025504
Influenza viruses cause annual seasonal epidemics and pandemics at irregular intervals. Several cases of human infections with avian and swine influenza viruses have been detected recently, warranting enhanced surveillance and the development of more effective countermeasures to address the pandemic potential of these viruses. The most effective countermeasure against influenza virus infection is the use of prophylactic vaccines. However, vaccines that are currently in use for seasonal influenza viruses have to be re-formulated and re-administered in a cumbersome process every year due to the antigenic drift of the virus. Furthermore, current seasonal vaccines are ineffective against novel pandemic strains. This paper reviews zoonotic influenza viruses with pandemic potential and technological advances towards better vaccines that induce broad and long lasting protection from influenza virus infection. Recent efforts have focused on the development of broadly protective/universal influenza virus vaccines that can provide immunity against drifted seasonal influenza virus strains but also against potential pandemic viruses.
Principi, Nicola; Senatore, Laura; Esposito, Susanna
Influenza is a very common disease among infants and young children, with a considerable clinical and socioeconomic impact. A significant number of health authorities presently recommend universal influenza vaccination for the pediatric population, but a large number of European health authorities is still reluctant to include influenza vaccination in their national vaccination programs. The reasons for this reluctance include the fact that the protection offered by the currently available vaccines is considered poor. This review shows that although future research could lead to an increase in the immunogenicity and potential efficacy of influenza vaccines, the available vaccines, even with their limits, assure sufficient protection in most subjects aged ≥ 6 months, thus reducing the total burden of influenza in young children and justifying the recommendation for the universal vaccination of the whole pediatric population. For younger subjects, the vaccination of their mother during pregnancy represents an efficacious strategy. PMID:26090704
García, Amos; Ortiz de Lejarazu, Raúl; Reina, Jordi; Callejo, Daniel; Cuervo, Jesús; Morano Larragueta, Raúl
ABSTRACT Influenza has a major impact on healthcare systems and society, but can be prevented using vaccination. The World Health Organization (WHO) currently recommends that influenza vaccines should include at least two virus A and one virus B lineage (trivalent vaccine; TIV). A new quadrivalent vaccine (QIV), which includes an additional B virus strain, received regulatory approval and is now recommended by several countries. The present study estimates the cost-effectiveness of replacing TIVs with QIV for risk groups and elderly population in Spain. A static, lifetime, multi-cohort Markov model with a one-year cycle time was adapted to assess the costs and health outcomes associated with a switch from TIV to QIV. The model followed a cohort vaccinated each year according to health authority recommendations, for the duration of their lives. National epidemiological data allowed the determination of whether the B strain included in TIVs matched the circulating one. Societal perspective was considered, costs and outcomes were discounted at 3% and one-way and probabilistic sensitivity analyses were performed. Compared to TIVs, QIV reduced more influenza cases and influenza-related complications and deaths during periods of B-mismatch strains in the TIV. The incremental cost-effectiveness ratio (ICER) was 8,748€/quality-adjusted life year (QALY). One-way sensitivity analysis showed mismatch with the B lineage included in the TIV was the main driver for ICER. Probabilistic sensitivity analysis shows ICER below 30,000€/QALY in 96% of simulations. Replacing TIVs with QIV in Spain could improve influenza prevention by avoiding B virus mismatch and provide a cost-effective healthcare intervention. PMID:27184622
Kerr, Stephen; Van Bennekom, Carla M; Mitchell, Allen A
Seasonal influenza vaccine is recommended for all pregnant women because of their increased risk for influenza-associated complications. In addition, receipt of influenza vaccine by women during pregnancy has been shown to protect their infants for several months after birth (1). As part of its case-control surveillance study of medications and birth defects, the Birth Defects Study of the Slone Epidemiology Center at Boston University has recorded data on vaccinations received during pregnancy since the 2005-06 influenza vaccination season. Among the 5,318 mothers of infants without major structural birth defects (control newborns) in this population, seasonal influenza vaccination coverage was approximately 20% in the seasons preceding the 2009-10 pandemic H1N1 (pH1N1) influenza season. During the 2009-10 influenza vaccination season, influenza vaccination coverage among pregnant women increased to 33%, and has increased modestly since then, to 41% during the 2013-14 season. Among pregnant women who received influenza vaccine during the 2013-14 season, 80% reported receiving their vaccine in a traditional health care setting, (e.g., the office of their obstetrician or primary care physician or their prenatal clinic) and 20% received it in a work/school, pharmacy/supermarket, or government setting. Incorporating routine administration of seasonal influenza vaccination into the management of pregnant women by their health care providers might increase coverage with this important public health intervention.
Although little has changed in vaccine technology for avian influenza virus (AIV) in the past 20 years, the approach to vaccination of poultry (chickens, turkeys and ducks) for avian influenza has evolved as highly pathogenic (HP) AIV has become endemic in several regions of the world. Vaccination f...
Avian influenza vaccines for poultry are based on hemagglutinin proteins and protection is specific to the vaccine subtype. Over 113 billion doses have been used between 2002 and 2010 for high pathogenicity avian influenza control. No universal vaccines are currently available. The majority of avian...
Uwemedimo, Omolara T; Findley, Sally E; Andres, Raquel; Irigoyen, Matilde; Stockwell, Melissa S
Few studies have examined potential factors that contribute to low influenza vaccination rates among minority children. This study aimed to assess the prevalence of early childhood influenza vaccination among young black and Latino children, living in inner-city neighborhoods, and examine the effects of child, caregiver and health system factors. Secondary data analysis was performed using a survey about medical home experiences conducted from May 2007-June 2008. The study sample was limited to children ≥6 months in any influenza season prior to the 2006-2007 influenza season. Bivariate analyses and multivariable logistic regression tested associations between influenza vaccination receipt and socio-demographic and health system characteristics. One-third of children received an influenza vaccination by the end of 2006-2007 season, while only 11% received a vaccination within their first season of eligibility. Black children were more likely than Latino children to have been vaccinated (50% vs. 31%, P<0.01) during their first few eligible seasons. Children whose mothers were older, proficient in English, and frequent users of healthcare were more likely to obtain vaccination. Child attendance at healthcare settings with immunization reminder systems was also positively correlated with influenza vaccination. Our findings suggest that initial vaccination receipt among minority children from inner-city communities might be improved by expanded influenza promotion activities targeting younger mothers or those with limited English proficiency. Strategies to increase the frequency of child's actual contact with the medical home, such as reminder systems, may be useful in improving uptake of influenza vaccination among inner-city, minority children.
Gotoh, Kensei; Ito, Yoshinori; Suzuki, Eitaro; Kaneko, Kenitiro; Kiuchi, Tetsuya; Ando, Hisami; Kimura, Hiroshi
Annual influenza vaccination is recommended for pediatric liver transplant recipients, who are at high risk of influenza-related complications. However, effectiveness and safety of vaccination may differ among influenza seasons in this population and have not been fully evaluated. Subjects comprised 38 pediatric liver transplant recipients with or without influenza vaccination through the 2006-2007, 2007-2008 and 2008-2009 influenza seasons. Recipients received inactivated trivalent (AH1/AH3/B) influenza vaccine, and comparisons were made to non-vaccinated recipients with regard to effectiveness and safety. No significant differences were seen between recipient groups for acute allograft rejection, acute febrile illness, or influenza virus infection. No serious systemic adverse events were observed in vaccinated recipients. Seroprotection rate (defined as the proportion of recipients with HI antibody titer ≥ 1:40), seroconversion rate (proportion of recipients with a ≥ 4-fold increase in HI titers), and geometric mean titers were mostly elevated after vaccination for the three influenza antigens in each season. These three indicators of immunogenicity showed similar results in both vaccinated recipients and vaccinated healthy children in the 2007-2008 season. These findings suggest that pediatric liver transplant patients may respond safely to inactivated seasonal influenza vaccines in a similar manner to healthy children, and effectiveness varies among influenza seasons.
Cheng, Allen C; Dwyer, Dominic E; Holmes, Mark; Irving, Lois B; Brown, Simon Ga; Waterer, Grant W; Korman, Tony M; Hunter, Cameron; Hewagama, Saliya; Friedman, Nadia D; Wark, Peter A; Simpson, Graham; Upham, John W; Bowler, Simon D; Senenayake, Sanjaya N; Kotsimbos, Tom C; Kelly, Paul M
The National Influenza Program aims to reduce serious morbidity and mortality from influenza by providing public funding for vaccination to at-risk groups. The Influenza Complications Alert Network (FluCAN) is a sentinel hospital-based surveillance program that operates at 14 sites in all states and territories in Australia. This report summarises the epidemiology of hospitalisations with confirmed influenza, estimates vaccine coverage and influenza vaccine protection against hospitalisation with influenza during the 2013 influenza season. In this observational study, cases were defined as patients admitted to one of the sentinel hospitals, with influenza confirmed by nucleic acid testing. Controls were patients who had acute respiratory illnesses who were test-negative for influenza. Vaccine effectiveness was estimated as 1 minus the odds ratio of vaccination in case patients compared with control patients, after adjusting for known confounders. During the period 5 April to 31 October 2012, 631 patients were admitted with confirmed influenza at the 14 FluCAN sentinel hospitals. Of these, 31% were more than 65 years of age, 9.5% were Indigenous Australians, 4.3% were pregnant and 77% had chronic co-morbidities. Influenza B was detected in 30% of patients. Vaccination coverage was estimated at 81% in patients more than 65 years of age but only 49% in patients aged less than 65 years with chronic comorbidities. Vaccination effectiveness against hospitalisation with influenza was estimated at 50% (95% confidence interval: 33%, 63%, P<0.001). We detected a significant number of hospital admissions with confirmed influenza in a national observational study. Vaccine coverage was incomplete in at-risk groups, particularly non-elderly patients with medical comorbidities. Our results suggest that the seasonal influenza vaccine was moderately protective against hospitalisation with influenza in the 2013 season.
Ropero-Álvarez, Alba María; Kurtis, Hannah J; Danovaro-Holliday, M Carolina; Ruiz-Matus, Cuauhtémoc; Andrus, Jon K
Background Seasonal influenza is a viral disease whose annual epidemics are estimated to cause three to five million cases of severe illness and 250,000 to 500,000 deaths worldwide. Vaccination is the main strategy for primary prevention. Methods To assess the status of influenza vaccination in the Americas, influenza vaccination data reported to the Pan American Health Organization (PAHO) through 2008 were analyzed. Results Thirty-five countries and territories administered influenza vaccine in their public health sector, compared to 13 countries in 2004. Targeted risk groups varied. Sixteen countries reported coverage among older adults, ranging from 21% to 100%; coverage data were not available for most countries and targeted populations. Some tropical countries used the Northern Hemisphere vaccine formulation and others used the Southern Hemisphere vaccine formulation. In 2008, approximately 166.3 million doses of seasonal influenza vaccine were purchased in the Americas; 30 of 35 countries procured their vaccine through PAHO's Revolving Fund. Conclusion Since 2004 there has been rapid uptake of seasonal influenza vaccine in the Americas. Challenges to fully implement influenza vaccination remain, including difficulties measuring coverage rates, variable vaccine uptake, and limited surveillance and effectiveness data to guide decisions regarding vaccine formulation and timing, especially in tropical countries. PMID:19778430
Bazhan, Sergei I.
By means of a designed epidemic model, we evaluated the influence of seasonal vaccination coverage as well as a potential universal vaccine with differing efficacy on the aftermath of seasonal and pandemic influenza. The results of the modeling enabled us to conclude that, to control a seasonal influenza epidemic with a reproduction coefficient R0 ≤ 1.5, a 35% vaccination coverage with the current seasonal influenza vaccine formulation is sufficient, provided that other epidemiology measures are regularly implemented. Increasing R0 level of pandemic strains will obviously require stronger intervention. In addition, seasonal influenza vaccines fail to confer protection against antigenically distinct pandemic influenza strains. Therefore, the necessity of a universal influenza vaccine is clear. The model predicts that a potential universal vaccine will be able to provide sufficient reliable (90%) protection against pandemic influenza only if its efficacy is comparable with the effectiveness of modern vaccines against seasonal influenza strains (70%–80%); given that at least 40% of the population has been vaccinated in advance, ill individuals have been isolated (observed), and a quarantine has been introduced. If other antiepidemic measures are absent, a vaccination coverage of at least 80% is required. PMID:27668256
VACCINE INFORMATION STATEMENT Hib Vaccine ( Haemophilus Influenzae Type b) What You Need to Know Many Vaccine Information ... vis 1 Why get vaccinated? Haemophilus influenzae type b (Hib) disease is a serious disease caused by ...
Beginning in Southeast Asia, in 2003, a multi-national epizootic outbreak of H5N1 highly pathogenic avian influenza (HPAI) was identified in commercial poultry and wild bird species. This lineage, originally identified in Southern China in 1996 and then Hong Kong in 1997, caused severe morbidity an...
Jimenez-Jorge, S; de Mateo, S; Delgado-Sanz, C; Pozo, F; Casas, I; Garcia-Cenoz, M; Castilla, J; Rodriguez, C; Vega, T; Quinones, C; Martinez, E; Vanrell, J M; Gimenez, J; Castrillejo, D; Altzibar, J M; Carril, F; Ramos, J M; Serrano, M C; Martinez, A; Torner, N; Perez, E; Gallardo, V; Larrauri, A
We aimed to estimate influenza vaccine effectiveness (VE) against laboratory-confirmed influenza during three influenza seasons (2010/11 to 2012/2013) in Spain using surveillance data and to compare the results with data obtained by the cycEVA study, the Spanish component of the Influenza Monitoring Vaccine Effectiveness (I-MOVE) network. We used the test-negative case–control design, with data from the Spanish Influenza Sentinel Surveillance System (SISS) or from the cycEVA study. Cases were laboratory-confirmed influenza patients with the predominant influenza virus of each season, and controls were those testing negative for any influenza virus. We calculated the overall and age-specific adjusted VE. Although the number of patients recorded in the SISS was three times higher than that in the cycEVA study, the quality of information for important variables, i.e. vaccination status and laboratory results, was high in both studies. Overall, the SISS and cycEVA influenza VE estimates were largely similar during the study period. For elderly patients (> 59 years), the SISS estimates were slightly lower than those of cycEVA, and estimates for children (0–14 years) were higher using SISS in two of the three seasons studied. Enhancing the SISS by collecting the date of influenza vaccination and reducing the percentage of patients with incomplete information would optimise the system to provide reliable annual influenza VE estimates to guide influenza vaccination policies.
Hoft, Daniel F; Belshe, Robert B
Influenza remains a major problem causing significant morbidity and mortality annually and periodic pandemics with the potential for 10-100 fold increased mortality. Conventional vaccines can be highly effective if generated each year to match currently circulating viruses. Ongoing research focuses on producing cross-protective vaccines that induce T cell and/ or antibody responses specific for highly conserved viral epitopes. The Saint Louis University Center for Vaccine Development (SLUCVD) is highly engaged in multiple efforts to generate universally relevant influenza vaccines.
Kang, Gloria J; Culp, Rachel K; Abbas, Kaja M
The study objective was to identify facilitators and barriers of parental attitudes and beliefs toward school-located influenza vaccination in the United States. In 2009, the Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention expanded their recommendations for influenza vaccination to include school-aged children. We conducted a systematic review of studies focused on facilitators and barriers of parental attitudes toward school-located influenza vaccination in the United States from 1990 to 2016. We reviewed 11 articles by use of the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) framework. Facilitators were free/low cost vaccination; having belief in vaccine efficacy, influenza severity, and susceptibility; belief that vaccination is beneficial, important, and a social norm; perception of school setting advantages; trust; and parental presence. Barriers were cost; concerns regarding vaccine safety, efficacy, equipment sterility, and adverse effects; perception of school setting barriers; negative physician advice of contraindications; distrust in vaccines and school-located vaccination programs; and health information privacy concerns. We identified the facilitators and barriers of parental attitudes and beliefs toward school-located influenza vaccination to assist in the evidence-based design and implementation of influenza vaccination programs targeted for children in the United States and to improve influenza vaccination coverage for population-wide health benefits.
Gasparini, Roberto; Amicizia, Daniela; Lai, Piero Luigi; Panatto, Donatella
Influenza viruses are adept in human populations. Indeed, they have the capacity to evade the immune system through mechanisms of mutations (antigenic drift) and major variations in surface protein expression (antigenic shift). When a major change occurs, the risk of a human pandemic arises. Three influenza pandemics occurred during the 20th century, the most serious being the Spanish influenza. The last pandemic of the past century occurred in 1968, and the responsible virus infected an estimated 1-3 million people throughout the world. The first pandemic of the present century occurred in 2009 and was sustained by a H1N1 strain (A/California/07/09). In 1997, a novel avian influenza virus, H5N1, first infected humans in China. Since its emergence, the H5N1 virus has spread from Asia to Europe and Africa, resulting in the infection of millions of poultry and wild birds. So far, 522 human cases and 322 deaths have been reported by the WHO. Many studies have therefore been performed to obtain efficacious and safe H5N1 vaccines. One of these is Aflunov(®). Aflunov is a prepandemic monovalent A/H5N1 influenza vaccine adjuvanted with MF59 produced by Novartis Vaccines and Diagnostics. In nonclinical studies conducted in rabbits, Aflunov proved to be well-tolerated, did not cause maternal or embryo-fetal toxicity, was not teratogenic, and had no effects on postnatal development. In clinical studies, Aflunov proved safe and well-tolerated in infants, children, adolescents, adults and the elderly. In the same subjects, the vaccine elicited robust immunogenicity against both homologous (A/Vietnam/1194/2004 clade 1) and heterologous viral strains (for instance, A/Indonesia/05/2005 or A/Turkey/15/2006) and induced immunologic memory. Thus, in 2010, the CHMP issued a positive opinion on Aflunov and in January 2011 Aflunov was given marketing authorization. This vaccine could be very useful in the event of adaptation of the H5N1 virus to humans, which could cause a new
Inactivated vaccines comprise 95% of all vaccine used for avian influenza virus (AIV) by dose. Optimizing the adjuvant is one way to improve vaccine efficacy. Inactivated vaccines were produced with beta-propiolactone inactivated A/chicken/BC/314514-1/2004 H7N3 low pathogenicity AIV and standardiz...
Castella, A; Argentero, P A; Lanszweert, A
Despite recommendations, influenza vaccination coverage in health professionals remains low throughout the world. In order to identify reasons for adherence or refusal we conducted a study within our hospital by means of interview questionnaires which were distributed to health care workers to reveal factors influencing acceptance or refusal of vaccination and to get suggestions to improve vaccination coverage. There is good overlap between our results and data obtainable from international literature: the main motivating factor for vaccination is personal protection against influenza, while only a significantly smaller part gave protection of patients as a reason. The main factors for not adhering to vaccination are belief the vaccine is not effective, influenza-related sick leave, fear of adverse effects and lack of availability. These data point out the need for more information concerning the importance of influenza infection within risk groups, the safety and effectiveness of the vaccine. Further, it is suitable to increase availability of the vaccine free of charge.
Kimura, Akiko C.; Nguyen, Christine N.; Higa, Jeffrey I.; Hurwitz, Eric L.; Vugia, Duc J.
Objectives. We examined barriers to influenza vaccination among long-term care facility (LTCF) health care workers in Southern California and developed simple, effective interventions to improve influenza vaccine coverage of these workers. Methods. In 2002, health care workers at LTCFs were surveyed regarding their knowledge and attitudes about influenza and the influenza vaccine. Results were used to develop 2 interventions, an educational campaign and Vaccine Day (a well-publicized day for free influenza vaccination of all employees at the worksite). Seventy facilities were recruited to participate in an intervention trial and randomly assigned to 4 study groups. Results. The combination of Vaccine Day and an educational campaign was most effective in increasing vaccine coverage (53% coverage; prevalence ratio [PR]=1.45; 95% confidence interval [CI]=1.24, 1.71, compared with 27% coverage in the control group). Vaccine Day alone was also effective (46% coverage; PR= 1.41; 95% CI=1.17, 1.71). The educational campaign alone was not effective in improving coverage levels (34% coverage; PR=1.18; 95% CI=0.93, 1.50). Conclusion. Influenza vaccine coverage of LTCF health care workers can be improved by providing free vaccinations at the worksite with a well-publicized Vaccine Day. PMID:17329659
Jegaskanda, Sinthujan; Amarasena, Thakshila H; Laurie, Karen L; Tan, Hyon-Xhi; Butler, Jeff; Parsons, Matthew S; Alcantara, Sheilajen; Petravic, Janka; Davenport, Miles P; Hurt, Aeron C; Reading, Patrick C; Kent, Stephen J
Yearly vaccination with the trivalent inactivated influenza vaccine (TIV) is recommended, since current vaccines induce little cross neutralization to divergent influenza strains. Whether the TIV can induce antibody-dependent cellular cytotoxicity (ADCC) responses that can cross-recognize divergent influenza virus strains is unknown. We immunized 6 influenza-naive pigtail macaques twice with the 2011-2012 season TIV and then challenged the macaques, along with 12 control macaques, serially with H1N1 and H3N2 viruses. We measured ADCC responses in plasma to a panel of H1 and H3 hemagglutinin (HA) proteins and influenza virus-specific CD8 T cell (CTL) responses using a sensitive major histocompatibility complex (MHC) tetramer reagent. The TIV was weakly immunogenic and, although binding antibodies were detected by enzyme-linked immunosorbent assay (ELISA), did not induce detectable influenza virus-specific ADCC or CTL responses. The H1N1 challenge elicited robust ADCC to both homologous and heterologous H1 HA proteins, but not influenza virus HA proteins from different subtypes (H2 to H7). There was no anamnestic influenza virus-specific ADCC or CTL response in vaccinated animals. The subsequent H3N2 challenge did not induce or boost ADCC either to H1 HA proteins or to divergent H3 proteins but did boost CTL responses. ADCC or CTL responses were not induced by TIV vaccination in influenza-naive macaques. There was a marked difference in the ability of infection compared to that of vaccination to induce cross-reactive ADCC and CTL responses. Improved vaccination strategies are needed to induce broad-based ADCC immunity to influenza.
Icardi, Giancarlo; Orsi, Andrea; Ceravolo, Antonella; Ansaldi, Filippo
Among the several strategies explored for (1) the enhancement of the immune response to influenza immunization, (2) the improvement of the vaccine acceptability and (3) the overcoming of the egg-dependency for vaccine production, intradermal administration of influenza vaccine emerges as a promising alternative to conventional intramuscular route, thanks to the recent availability of new delivery devices and the perception of advantages in terms of immunogenicity, safety, reduction of antigen content and acceptability. Data from clinical trials performed in children, adults <60 y and elderly people and post-marketing surveillance demonstrate that actually, licensed intradermal influenza vaccines, Intanza™ 9 and 15 µg and Fluzone™ Intradermal, administered by the microinjection system Soluvia™, show an excellent acceptability, tolerability and safety profile. Formulations containing 9 and 15 μg per strain demonstrate, respectively, comparable and superior immunogenicity than conventional intramuscular vaccines. Licensed intradermal influenza vaccines can be considered a valid alternative to standard intramuscular vaccination offering significant advantages in low-responder populations and helping to increase influenza vaccination coverage rates especially in people with fear of needles or high apprehension associated with annual vaccination. PMID:22293531
... Proclamation 8472--National Influenza Vaccination Week, 2010 #0; #0; #0; Presidential Documents #0; #0; #0;#0...;Title 3-- #0;The President ] Proclamation 8472 of January 8, 2010 National Influenza Vaccination Week... week presents a window of opportunity for us to prevent a possible third wave of H1N1 flu in the...
Chou, Cheng-Hsiu; Liou, Wen-Ping; Hu, Kun-I; Loh, Ching-Hui; Chou, Chih-Chieh; Chen, Yeong-Hwang
The etiology of Bell's palsy is often unknown. We present herein two cases of adults who developed a Bell's palsy following the administration of an influenza vaccine. While the incidence is low, with the widespread recommendation for annual influenza vaccines, patients should be apprised of the possibility of this complication and the benefit of early treatment.
Gargano, Lisa M; Underwood, Natasha L; Sales, Jessica M; Seib, Katherine; Morfaw, Christopher; Murray, Dennis; DiClemente, Ralph J; Hughes, James M
In 2011-2012, only 34% of 13-17 years olds in the United States (US) received seasonal influenza vaccine. Little is known about the link between parents' sources of health information, their vaccine-related attitudes, and vaccination of their adolescent against influenza. This study seeks to determine the relationship between number of sources of information on influenza vaccine, parental attitudes toward influenza vaccine, and influenza vaccine uptake in adolescents. We conducted a telephone and web-based survey among US parents of students enrolled in 6 middle and 5 high schools in Georgia. Bivariate and multivariable analyses were conducted to examine associations between the number of information sources about influenza vaccine and vaccine receipt and whether parent vaccine-related attitudes act as a mediator. The most commonly reported sources of information were: a physician/medical professional (95.0%), a family member or friend (80.6%), and television (77.2%). Parents who had higher attitude scores toward influenza vaccine were 5 times as likely to report their adolescent had ever received influenza vaccine compared to parents who had lower attitude scores (adjusted odds ratio (aOR) 5.1; 95% confidence intervals (CI) 3.1-8.4; P < 0.01). Parent vaccine-related attitudes were a significant mediator of the relationship between sources of information and vaccine receipt. In light of the low response rate and participation in an adolescent vaccination intervention, findings may not be generalizable to other populations. This study shows the importance of multiple sources of information in influencing parental decision-making about influenza vaccine for adolescents. Harnessing the power of mass media and family members and friends as health advocates for influenza vaccination can potentially help increase vaccination coverage of adolescents.
Avelino-Silva, Vivian Iida; Avelino-Silva, Thiago Junqueira; Miraglia, Joao Luiz; Miyaji, Karina Takesaki; Jacob-Filho, Wilson; Lopes, Marta Heloisa
OBJECTIVES: Population aging raises concerns regarding the increases in the rates of morbidity and mortality that result from influenza and its complications. Although vaccination is the most important tool for preventing influenza, vaccination program among high-risk groups has not reached its predetermined aims in several settings. This study aimed to evaluate the impacts of clinical and demographic factors on vaccine compliance among the elderly in a setting that includes a well-established annual national influenza vaccination campaign. METHODS: This cross-sectional study included 134 elderly patients who were regularly followed in an academic medical institution and who were evaluated for their influenza vaccination uptake within the last five years; in addition, the demographic and clinical characteristics and the reasons for compliance or noncompliance with the vaccination program were investigated. RESULTS: In total, 67.1% of the participants received the seasonal influenza vaccine in 2009. Within this vaccination-compliant group, the most common reason for vaccine uptake was the annual nationwide campaign (52.2%; 95% CI: 41.4–62.9%); compared to the noncompliant group, a higher percentage of compliant patients had been advised by their physician to take the vaccine (58.9% vs. 34.1%; p<0.01). CONCLUSION: The education of patients and health care professionals along with the implementation of immunization campaigns should be evaluated and considered by health authorities as essential for increasing the success rate of influenza vaccination compliance among the elderly. PMID:22189726
Despite the benefits of routine vaccination of newborns are known and widely documented, in recent years we are observing a gradual increase in the number of parents who express doubts and concerns about the safety of vaccines and the real need to submit their children to vaccinations included in the national recommendations. This attitude is reinforced by the current epidemiological profile, in Western countries, of many vaccine preventable diseases, accompanied by a low risk perception among parents. Institutions and all the actors involved in vaccination programs have a duty to investigate the reasons for the loss of confidence in vaccination among the population in order to identify and implement appropriate and effective interventions. The improvement of vaccination should, theoretically, goes on a double track, placing side by side the provision of effective vaccines, safe and necessary, and interventions designed to increase demand for vaccination among the population, improve access to vaccination services, improve the system as a whole. But to actually improve the vaccinations' offer it is necessary also to provide interventions aimed at regaining the confidence of the population in relation to vaccination and the institutions that promote them. Particular attention should be given to the aspects of communication and risk communication.
... 21 Food and Drugs 7 2010-04-01 2010-04-01 false Inactivated influenza vaccine, general safety test... Inactivated influenza vaccine, general safety test. For inactivated influenza vaccine, the general safety test... subcutaneous or intraperitoneal injection of 5.0 milliliters of inactivated influenza vaccine into each...
... 21 Food and Drugs 7 2012-04-01 2012-04-01 false Inactivated influenza vaccine, general safety test... Inactivated influenza vaccine, general safety test. For inactivated influenza vaccine, the general safety test... subcutaneous or intraperitoneal injection of 5.0 milliliters of inactivated influenza vaccine into each...
... 21 Food and Drugs 7 2014-04-01 2014-04-01 false Inactivated influenza vaccine, general safety test... Inactivated influenza vaccine, general safety test. For inactivated influenza vaccine, the general safety test... subcutaneous or intraperitoneal injection of 5.0 milliliters of inactivated influenza vaccine into each...
... 21 Food and Drugs 7 2013-04-01 2013-04-01 false Inactivated influenza vaccine, general safety test... Inactivated influenza vaccine, general safety test. For inactivated influenza vaccine, the general safety test... subcutaneous or intraperitoneal injection of 5.0 milliliters of inactivated influenza vaccine into each...
... 21 Food and Drugs 7 2011-04-01 2010-04-01 true Inactivated influenza vaccine, general safety test... Inactivated influenza vaccine, general safety test. For inactivated influenza vaccine, the general safety test... subcutaneous or intraperitoneal injection of 5.0 milliliters of inactivated influenza vaccine into each...
Yewdell, Jonathan W
Year in and year out, influenza viruses exact a deadly and expensive toll on humanity. Current vaccines simply do not keep pace with viral immune evasion, providing partial protection, at best, among various age groups. A quantum leap in understanding the basic principles of the adaptive and innate immune responses to influenza viruses offers the opportunity to develop vaccines that forestall, and potentially ultimately defeat, influenza virus antigenic variation.
Hashem, Anwar M.
Current influenza vaccines afford substantial protection in humans by inducing strain-specific neutralizing antibodies (Abs). Most of these Abs target highly variable immunodominant epitopes in the globular domain of the viral hemagglutinin (HA). Therefore, current vaccines may not be able to induce heterosubtypic immunity against the divergent influenza subtypes. The identification of broadly neutralizing Abs (BnAbs) against influenza HA using recent technological advancements in antibody libraries, hybridoma, and isolation of single Ab-secreting plasma cells has increased the interest in developing a universal influenza vaccine as it could provide life-long protection. While these BnAbs can serve as a source for passive immunotherapy, their identification represents an important step towards the design of such a universal vaccine. This review describes the recent advances and approaches used in the development of universal influenza vaccine based on highly conserved HA regions identified by BnAbs. PMID:25785268
Hashem, Anwar M
Current influenza vaccines afford substantial protection in humans by inducing strain-specific neutralizing antibodies (Abs). Most of these Abs target highly variable immunodominant epitopes in the globular domain of the viral hemagglutinin (HA). Therefore, current vaccines may not be able to induce heterosubtypic immunity against the divergent influenza subtypes. The identification of broadly neutralizing Abs (BnAbs) against influenza HA using recent technological advancements in antibody libraries, hybridoma, and isolation of single Ab-secreting plasma cells has increased the interest in developing a universal influenza vaccine as it could provide life-long protection. While these BnAbs can serve as a source for passive immunotherapy, their identification represents an important step towards the design of such a universal vaccine. This review describes the recent advances and approaches used in the development of universal influenza vaccine based on highly conserved HA regions identified by BnAbs.
Deng, Lei; Cho, Ki Joon; Fiers, Walter; Saelens, Xavier
The successful isolation of a human influenza virus in 1933 was soon followed by the first attempts to develop an influenza vaccine. Nowadays, vaccination is still the most effective method to prevent human influenza disease. However, licensed influenza vaccines offer protection against antigenically matching viruses, and the composition of these vaccines needs to be updated nearly every year. Vaccines that target conserved epitopes of influenza viruses would in principle not require such updating and would probably have a considerable positive impact on global human health in case of a pandemic outbreak. The extracellular domain of Matrix 2 (M2e) protein is an evolutionarily conserved region in influenza A viruses and a promising epitope for designing a universal influenza vaccine. Here we review the seminal and recent studies that focused on M2e as a vaccine antigen. We address the mechanism of action and the clinical development of M2e-vaccines. Finally, we try to foresee how M2e-based vaccines could be implemented clinically in the future.
Deng, Lei; Cho, Ki Joon; Fiers, Walter; Saelens, Xavier
The successful isolation of a human influenza virus in 1933 was soon followed by the first attempts to develop an influenza vaccine. Nowadays, vaccination is still the most effective method to prevent human influenza disease. However, licensed influenza vaccines offer protection against antigenically matching viruses, and the composition of these vaccines needs to be updated nearly every year. Vaccines that target conserved epitopes of influenza viruses would in principle not require such updating and would probably have a considerable positive impact on global human health in case of a pandemic outbreak. The extracellular domain of Matrix 2 (M2e) protein is an evolutionarily conserved region in influenza A viruses and a promising epitope for designing a universal influenza vaccine. Here we review the seminal and recent studies that focused on M2e as a vaccine antigen. We address the mechanism of action and the clinical development of M2e-vaccines. Finally, we try to foresee how M2e-based vaccines could be implemented clinically in the future. PMID:26344949
Kim, Hyunsuh; Velkov, Tony; Camuglia, Sarina; Rockman, Steven P; Tannock, Gregory A
Seasonal inactivated influenza vaccines are usually trivalent or quadrivalent and are prepared from accredited seed viruses. Yields of influenza A seed viruses can be enhanced by gene reassortment with high-yielding donor strains, but similar approaches for influenza B seed viruses have been largely unsuccessful. For vaccine manufacture influenza B seed viruses are usually adapted for high-growth by serial passage. Influenza B antigen yields so obtained are often unpredictable and selection of influenza B seed viruses by this method can be a rate-limiting step in seasonal influenza vaccine manufacture. We recently have shown that selection of stable cold-adapted mutants from seasonal epidemic influenza B viruses is associated with improved growth. In this study, specific mutations were identified that were responsible for growth enhancement as a consequence of adaptation to growth at lower temperatures. Molecular analysis revealed that the following mutations in the HA, NP and NA genes are required for enhanced viral growth: G156/N160 in the HA, E253, G375 in the NP and T146 in the NA genes. These results demonstrate that the growth of seasonal influenza B viruses can be optimized or improved significantly by specific gene modifications.
Cheng, Allen C; Kotsimbos, Tom; Kelly, Paul M
We provide estimates of the influenza vaccine protection against hospitalisation with laboratory-confirmed influenza in the 2014 Australian season where the A/H1N1/pdm09 strain predominated. This was performed using a case-test negative study design as part of a national sentinel surveillance system in Australia. Vaccine effectiveness was estimated as (1-OR)×100% where the odds ratio of vaccination in cases vs test negative participants was estimated from a conditional logistic regression. Between April and November, 1692 adult patients were admitted with laboratory-confirmed influenza. Vaccine effectiveness was estimated from 1283 patients with influenza and 1116 test negative patients where vaccination status was ascertained. Vaccination was associated with a reduction in the risk of hospitalisation with influenza of 51.5% (95% CI: 41.6%, 59.7%) in all patients, and a reduction of 50.7% (95% CI: 40.1%, 59.3%) in the target population for vaccination. We estimate that the influenza vaccine was moderately protective against hospitalisation with laboratory-confirmed influenza during the 2014 influenza season in Australia.
Background Influenza viruses are a major cause of morbidity and mortality worldwide. Vaccination remains a powerful tool for preventing or mitigating influenza outbreaks. Yet, vaccine supplies and daily administration capacities are limited, even in developed countries. Understanding how such constraints can alter the mitigating effects of vaccination is a crucial part of influenza preparedness plans. Mathematical models provide tools for government and medical officials to assess the impact of different vaccination strategies and plan accordingly. However, many existing models of vaccination employ several questionable assumptions, including a rate of vaccination proportional to the population at each point in time. Methods We present a SIR-like model that explicitly takes into account vaccine supply and the number of vaccines administered per day and places data-informed limits on these parameters. We refer to this as the non-proportional model of vaccination and compare it to the proportional scheme typically found in the literature. Results The proportional and non-proportional models behave similarly for a few different vaccination scenarios. However, there are parameter regimes involving the vaccination campaign duration and daily supply limit for which the non-proportional model predicts smaller epidemics that peak later, but may last longer, than those of the proportional model. We also use the non-proportional model to predict the mitigating effects of variably timed vaccination campaigns for different levels of vaccination coverage, using specific constraints on daily administration capacity. Conclusions The non-proportional model of vaccination is a theoretical improvement that provides more accurate predictions of the mitigating effects of vaccination on influenza outbreaks than the proportional model. In addition, parameters such as vaccine supply and daily administration limit can be easily adjusted to simulate conditions in developed and developing
Murcia, Pablo R; Baillie, Gregory J; Stack, J Conrad; Jervis, Carley; Elton, Debra; Mumford, Jennifer A; Daly, Janet; Kellam, Paul; Grenfell, Bryan T; Holmes, Edward C; Wood, James L N
Influenza A viruses are characterized by their ability to evade host immunity, even in vaccinated individuals. To determine how prior immunity shapes viral diversity in vivo, we studied the intra- and interhost evolution of equine influenza virus in vaccinated horses. Although the level and structure of genetic diversity were similar to those in naïve horses, intrahost bottlenecks may be more stringent in vaccinated animals, and mutations shared among horses often fall close to putative antigenic sites.
To, K W; Lai, A; Lee, K C K; Koh, D; Lee, S S
Seasonal influenza vaccine uptake rate of healthcare workers (HCWs) varies widely from <5% to >90% worldwide. Perception of vaccine efficacy and side-effects are conventional factors affecting the uptake rates. These factors may operate on a personal and social level, impacting the attitudes and behaviours of HCWs. Vaccination rates were also under the influence of the occurrence of other non-seasonal influenza pandemics such as avian influenza. Different strategies have been implemented to improve vaccine uptake, with important ones including the enforcement of the local authority's recommendations, promulgation of practice guidelines, and mandatory vaccination polices. Practised in some regions in North America, mandatory policies have led to higher vaccination rate, but are not problem-free. The effects of conventional educational programmes and campaigns are in general of modest impact only. Availability of convenient vaccination facilities, such as mobile vaccination cart, and role models of senior HCWs receiving vaccination are among some strategies which have been observed to improve vaccination uptake rate. A multi-faceted approach is thus necessary to persuade HCWs to participate in a vaccination programme, especially in areas with low uptake rate.
Jagadesh, Anitha; Salam, Abdul Ajees Abdul; Mudgal, Piya Paul; Arunkumar, Govindakarnavar
Influenza, the most common infectious disease, poses a great threat to human health because of its highly contagious nature and fast transmissibility, often leading to high morbidity and mortality. Effective vaccination strategies may aid in the prevention and control of recurring epidemics and pandemics associated with this infectious disease. However, antigenic shifts and drifts are major concerns with influenza virus, requiring effective global monitoring and updating of vaccines. Current vaccines are standardized primarily based on the amount of hemagglutinin, a major surface antigen, which chiefly constitutes these preparations along with the varying amounts of neuraminidase (NA). Anti-influenza drugs targeting the active site of NA have been in use for more than a decade now. However, NA has not been approved as an effective antigenic component of the influenza vaccine because of standardization issues. Although some studies have suggested that NA antibodies are able to reduce the severity of the disease and induce a long-term and cross-protective immunity, a few major scientific issues need to be addressed prior to launching NA-based vaccines. Interestingly, an increasing number of studies have shown NA to be a promising target for future influenza vaccines. This review is an attempt to consolidate studies that reflect the strength of NA as a suitable vaccine target. The studies discussed in this article highlight NA as a potential influenza vaccine candidate and support taking the process of developing NA vaccines to the next stage.
Arinaminpathy, Nimalan; Kim, Inkyu Kevin; Gargiullo, Paul; Haber, Michael; Foppa, Ivo M; Gambhir, Manoj; Bresee, Joseph
With influenza vaccination rates in the United States recently exceeding 45% of the population, it is important to understand the impact that vaccination is having on influenza transmission. In this study, we used a Bayesian modeling approach, combined with a simple dynamical model of influenza transmission, to estimate this impact. The combined framework synthesized evidence from a range of data sources relating to influenza transmission and vaccination in the United States. We found that, for seasonal epidemics, the number of infections averted ranged from 9.6 million in the 2006-2007 season (95% credible interval (CI): 8.7, 10.9) to 37.2 million (95% CI: 34.1, 39.6) in the 2012-2013 season. Expressed in relative terms, the proportion averted ranged from 20.8% (95% CI: 16.8, 24.3) of potential infections in the 2011-2012 season to 47.5% (95% CI: 43.7, 50.8) in the 2008-2009 season. The percentage averted was only 1.04% (95% CI: 0.15, 3.2) for the 2009 H1N1 pandemic, owing to the late timing of the vaccination program in relation to the pandemic in the Northern hemisphere. In the future, further vaccination coverage, as well as improved influenza vaccines (especially those offering better protection in the elderly), could have an even stronger effect on annual influenza epidemics.
Halsey, Neal A; Talaat, Kawsar R; Greenbaum, Adena; Mensah, Eric; Dudley, Matthew Z; Proveaux, Tina; Salmon, Daniel A
Most influenza vaccines are generally safe, but influenza vaccines can cause rare serious adverse events. Some adverse events, such as fever and febrile seizures, are more common in children than adults. There can be differences in the safety of vaccines in different populations due to underlying differences in genetic predisposition to the adverse event. Live attenuated vaccines have not been studied adequately in children under 2 years of age to determine the risks of adverse events; more studies are needed to address this and several other priority safety issues with all influenza vaccines in children. All vaccines intended for use in children require safety testing in the target age group, especially in young children. Safety of one influenza vaccine in children should not be extrapolated to assumed safety of all influenza vaccines in children. The low rates of adverse events from influenza vaccines should not be a deterrent to the use of influenza vaccines because of the overwhelming evidence of the burden of disease due to influenza in children.
Rodgers, Loren; Pabst, Laura J; Zhu, Liping; Chaves, Sandra S
Annual influenza vaccination is recommended for everyone ≥ 6 months in the U.S. During the 2013-14 influenza season, in addition to trivalent influenza vaccines, quadrivalent vaccines were available, protecting against two influenza A and two influenza B viruses. We analyzed 1,976,443 immunization records from six sentinel sites to compare influenza vaccine usage among children age 6 months-18 years. A total of 983,401 (49.8%) influenza vaccine doses administered were trivalent and 920,333 (46.6%) were quadrivalent (unknown type: 72,709). Quadrivalent vaccine administration varied by age and was least frequent among those <2 years of age.
Xiang, Kui; Ying, Guan; Yan, Zhou; Shanshan, Yan; Lei, Zhang; Hongjun, Li; Maosheng, Sun
Influenza virus (IFV) infection causes serious health problems and heavy financial burdens each year worldwide. The classical inactivated influenza virus vaccine (IIVV) and live attenuated influenza vaccine (LAIV) must be updated regularly to match the new strains that evolve due to antigenic drift and antigenic shift. However, with the discovery of broadly neutralizing antibodies that recognize conserved antigens, and the CD8(+) T cell responses targeting viral internal proteins nucleoprotein (NP), matrix protein 1 (M1) and polymerase basic 1 (PB1), it is possible to develop a universal influenza vaccine based on the conserved hemagglutinin (HA) stem, NP, and matrix proteins. Recombinant adenovirus (rAd) is an ideal influenza vaccine vector because it has an ideal stability and safety profile, induces balanced humoral and cell-mediated immune responses due to activation of innate immunity, provides 'self-adjuvanting' activity, can mimic natural IFV infection, and confers seamless protection against mucosal pathogens. Moreover, this vector can be developed as a low-cost, rapid-response vaccine that can be quickly manufactured. Therefore, an adenovirus vector encoding conserved influenza antigens holds promise in the development of a universal influenza vaccine. This review will summarize the progress in adenovirus-vectored universal flu vaccines and discuss future novel approaches.
Murphy, Timothy F
Infections due to nontypeable Haemophilus influenzae result in enormous global morbidity in two clinical settings: otitis media in children and respiratory tract infections in adults with chronic obstructive pulmonary disease (COPD). Recurrent otitis media affects up to 20% of children and results in hearing loss, delays in speech and language development and, in developing countries, chronic suppurative otitis media. Infections in people with COPD result in clinic and emergency room visits, hospital admissions, and respiratory failure. An effective vaccine would prevent morbidity, help control health care costs, and reduce antibiotic use, a major contributor to the global crisis in bacterial antibiotic resistance. The widespread use of the pneumococcal conjugate vaccines is causing a relative increase in H. influenzae otitis media. The partial protection against H. influenzae otitis media induced by the pneumococcal H. influenzae protein D conjugate vaccine represents a proof of principle of the feasibility of a vaccine for nontypeable H. influenzae. An ideal vaccine antigen should be conserved among strains, have abundant epitopes on the bacterial surface, be immunogenic, and induce protective immune responses. Several surface proteins of H. influenzae have been identified as potential vaccine candidates and are in various stages of development. With continued research, progress toward a broadly effective vaccine to prevent infections caused by nontypeable H. influenzae is expected over the next several years.
Xiang, Kui; Ying, Guan; Yan, Zhou; Shanshan, Yan; Lei, Zhang; Hongjun, Li; Maosheng, Sun
Influenza virus (IFV) infection causes serious health problems and heavy financial burdens each year worldwide. The classical inactivated influenza virus vaccine (IIVV) and live attenuated influenza vaccine (LAIV) must be updated regularly to match the new strains that evolve due to antigenic drift and antigenic shift. However, with the discovery of broadly neutralizing antibodies that recognize conserved antigens, and the CD8+ T cell responses targeting viral internal proteins nucleoprotein (NP), matrix protein 1 (M1) and polymerase basic 1 (PB1), it is possible to develop a universal influenza vaccine based on the conserved hemagglutinin (HA) stem, NP, and matrix proteins. Recombinant adenovirus (rAd) is an ideal influenza vaccine vector because it has an ideal stability and safety profile, induces balanced humoral and cell-mediated immune responses due to activation of innate immunity, provides ‘self-adjuvanting’ activity, can mimic natural IFV infection, and confers seamless protection against mucosal pathogens. Moreover, this vector can be developed as a low-cost, rapid-response vaccine that can be quickly manufactured. Therefore, an adenovirus vector encoding conserved influenza antigens holds promise in the development of a universal influenza vaccine. This review will summarize the progress in adenovirus-vectored universal flu vaccines and discuss future novel approaches. PMID:25876176
Hovden, Arnt-Ove; Cox, Rebecca Jane; Haaheim, Lars Reinhardt
Influenza is a major respiratory pathogen, which exerts a huge human and economic toll on society. Influenza is a vaccine preventable disease, however, the vaccine strains must be annually updated due to the continuous antigenic changes in the virus. Inactivated influenza vaccines have been used for over 50 years and have an excellent safety record. Annual vaccination is therefore recommended for all individuals with serious medical conditions, like COPD, and protects the vaccinee against influenza illness and also against hospitalization and death. In COPD patients, influenza infection can lead to exacerbations resulting in reduced quality of life, hospitalization and death in the most severe cases. Although there is only limited literature on the use of influenza vaccination solely in COPD patients, there is clearly enough evidence to recommend annual vaccination in this group. This review will focus on influenza virus and prophylaxis with inactivated influenza vaccines in COPD patients and other "at risk" groups to reduce morbidity, save lives, and reduce health care costs.
Blank, Patricia R; Szucs, Thomas D
The clinical and economic burden of seasonal influenza is frequently underestimated. The cornerstone of controlling and preventing influenza is vaccination. National and international guidelines aim to implement immunization programs and targeted vaccination-coverage rates, which should help to enhance the vaccine uptake, especially in the at-risk population. This review purposes to highlight the vaccination guidelines and the actual vaccination situation in four target groups (the elderly, people with underlying chronic conditions, healthcare workers and children) from a European point of view.
Herbinger, Karl-Heinz; von Sonnenburg, Frank; Nothdurft, Hans Dieter; Perona, Pamela; Borkowski, Astrid; Fragapane, Elena; Nicolay, Uwe; Clemens, Ralf
An investigational tetravalent vaccine combining pre-pandemic, MF59®-adjuvanted A/H5N1 vaccine with non-adjuvanted, trivalent, seasonal influenza vaccine has been developed, which has the potential to be used for pre-pandemic priming and to improve levels of compliance and coverage. It is important to determine whether the safety and immunogenicity of the combination vaccine is equivalent to that of the two separate vaccines when administered concomitantly. Healthy adults (n = 601) were randomly assigned to three vaccination groups to receive either: (1) tetravalent vaccine and placebo concomitantly (in separate arms) on Day 1, followed by A/H5N1 vaccine on Day 22; (2) A/H5N1 vaccine and placebo concomitantly on Day 1, followed by tetravalent vaccine on Day 22; or (3) A/H5N1 and seasonal vaccines concomitantly on Day 1, followed by A/H5N1 vaccine on Day 22. Antibody responses were measured using single radial hemolysis (SRH), haemagglutination inhibition (HI), and microneutralization (MN) assays on Days 1, 22, and 43. Solicited adverse reactions were recorded for seven days after vaccination. Spontaneous adverse events were recorded throughout the study. The tetravalent vaccine elicited antibody titers equivalent to those for separate A/H5N1 and seasonal vaccines, and sufficient to meet the European licensure criteria against A/H5N1 and all three seasonal strains. Local and systemic reactions were mainly mild to moderate. No vaccine-related serious adverse events occurred. These findings demonstrate that MF59-adjuvanted A/H5N1 and seasonal influenza vaccines had an acceptable safety profile and could be effectively administered as a tetravalent formulation, supporting the possibility of integrating pre-pandemic priming into seasonal influenza vaccination programs. PMID:24047817
Kreijtz, Joost H C M; Osterhaus, Albert D M E; Rimmelzwaan, Guus F
Influenza viruses of the H5N1 subtype cause an ever-increasing number of bird-to-human transmissions and a pandemic outbreak caused by these viruses is imminent. Therefore, the availability of safe and effective vaccines is highly desirable and their development considered a priority. However, using production and use of seasonal influenza vaccine as template for the production of pandemic H5N1 vaccines did not yield effective vaccines. High antigen doses were required to induce appreciable antibody responses. In addition, limited production capacity and long production times are other disadvantages of conventional influenza vaccine preparations. Here, we review recent developments that will contribute to a more rapid availability of sufficient doses of highly efficacious and safe pandemic influenza vaccines. The new developments include the establishment of novel methods to prepare vaccine strains, novel production technologies and the use of novel adjuvants and alternative vaccine formulations.
Kim, Han-Joon; Jeon, Sang-Won; Yoon, Ho-Kyoung
Human influenza is a contagious respiratory illness caused by the influenza virus. The influenza vaccination is recommended annually, but several adverse effects related to allergic reactions have been reported. Panic attacks are also known to occur, but no case of a panic attack adverse effect has been reported in South Korea. We present two cases of panic disorder patients whose symptoms were aggravated by the influenza vaccination. We assumed that dysregulation of T-lymphocytes in panic disorder patients could have a role in activating various kinds of cytokines and chemokines, which then can lead to panic attack aggravation. PMID:27776395
... Vaccines--Amendment Authority: 42 U.S.C. 247d-6d. ACTION: Notice of amendment to the September 28, 2009... and Emergency Preparedness Act for H5N1, H2, H6, H7, H9 and 2009-H1N1 Vaccines: Whereas there are or... September 28, 2009 declaration extended through February 28, 2010 for vaccines against influenza...
Mossad, Sherif B
Last year, the influenza vaccine did not match the circulating strains very well, and its overall protective efficacy was only 40%. All three antigens contained in the 2008-2009 vaccine are new. Surveillance data from the Southern Hemisphere during the summer of 2008 show that this vaccine is expected to match well the circulating strains in the Northern Hemisphere.
Different strategies for the management of influenza epidemics are particularly important in elderly population. High morbidity and mortality rates are associated with influenza in the elderly, and annual vaccination against flu is considered to be the best cost-effective strategy. However, its efficiency is reduced in older adults and only half of them are protected. Several studies show that vaccinating healthcare workers is an efficient way of decreasing mortality rates in nursing home residents within influenza season. National and international public health authorities recommend therefore healthcare worker vaccinations for up to 5 years. However, influenza healthcare worker vaccination coverages are still low. Here we summarize data regarding the justification of healthcare worker vaccination, the efficiency of this strategy, the reasons of the reluctance of vaccination, the means and results of interventional programs and, then, focus on the debate of a mandatory healthcare worker influenza vaccination. Because several interventional programs are efficient but still need high financial and human support, only a strong political-will can improve this chosen strategy.
Chaussee, Michael S; Sandbulte, Heather R; Schuneman, Margaret J; Depaula, Frank P; Addengast, Leslie A; Schlenker, Evelyn H; Huber, Victor C
Mortality associated with influenza virus super-infections is frequently due to secondary bacterial complications. To date, super-infections with Streptococcus pyogenes have been studied less extensively than those associated with Streptococcus pneumoniae. This is significant because a vaccine for S. pyogenes is not clinically available, leaving vaccination against influenza virus as our only means for preventing these super-infections. In this study, we directly compared immunity induced by two types of influenza vaccine, either inactivated influenza virus (IIV) or live, attenuated influenza virus (LAIV), for the ability to prevent super-infections. Our data demonstrate that both IIV and LAIV vaccines induce similar levels of serum antibodies, and that LAIV alone induces IgA expression at mucosal surfaces. Upon super-infection, both vaccines have the ability to limit the induction of pro-inflammatory cytokines within the lung, including IFN-γ which has been shown to contribute to mortality in previous models of super-infection. Limiting expression of these pro-inflammatory cytokines within the lungs subsequently limits recruitment of macrophages and neutrophils to pulmonary surfaces, and ultimately protects both IIV- and LAIV-vaccinated mice from mortality. Despite their overall survival, both IIV- and LAIV-vaccinated mice demonstrated levels of bacteria within the lung tissue that are similar to those seen in unvaccinated mice. Thus, influenza virus:bacteria super-infections can be limited by vaccine-induced immunity against influenza virus, but the ability to prevent morbidity is not complete.
Equine influenza (EI) is a major respiratory disease of horses, which is still causing substantial outbreaks worldwide despite several decades of surveillance and prevention. Alongside quarantine procedures, vaccination is widely used to prevent or limit spread of the disease. The panel of EI vaccines commercially available is probably one of the most varied, including whole inactivated virus vaccines, Immuno-Stimulating Complex adjuvanted vaccines (ISCOM and ISCOM-Matrix), a live attenuated equine influenza virus (EIV) vaccine and a recombinant poxvirus-vectored vaccine. Several other strategies of vaccination are also evaluated. This systematic review reports the advances of EI vaccines during the last few years as well as some of the mechanisms behind the inefficient or sub-optimal response of horses to vaccination. PMID:26344892
Sullivan, K M; Monto, A S; Foster, D A
Four inactivated influenza vaccines (containing the recommended antigens for the 1985-1986 influenza season) of various antigenic concentration levels were randomly administered to 140 study participants. The effect of the increasing antigen concentration resulted in significantly higher influenza hemagglutination inhibition (HI) antibody levels 3 weeks after vaccination for the A/H1N1 antigen but not for the A/H3N2 or B antigens. Also, at 3 weeks after vaccination, there were significantly lower antibody titer levels associated with increasing age for the A/H1N1 and B antigens (adjusting for the prevaccination antibody titer and antigen content).
Reber, Adrian J.; Chirkova, Tatiana; Kim, Jin Hyang; Cao, Weiping; Biber, Renata; Shay, David K.; Sambhara, Suryaprakash
Influenza is an important contributor to morbidity and mortality worldwide. Accumulation of genetic mutations termed antigenic drift, allows influenza viruses to inflict yearly epidemics that may result in 250,000 to 500,000 deaths annually. Over 90% of influenza-related deaths occur in the older adult population. This is at least in part a result of increasing dysregulation of the immune system with age, termed immunosenescence. This dysregulation results in reduced capacity to cope with infections and decreased responsiveness to vaccination. The older adult population is in dire need of improved vaccines capable of eliciting protective responses in the face of a waning immune system. This review focuses on the status of immunity, responses to influenza vaccination, and strategies that are currently being explored to elicit enhanced immune responses in this high risk population. PMID:22500272
Flannery, Brendan; Thompson, Mark G.; Gaglani, Manjusha; Jackson, Michael L.; Monto, Arnold S.; Nowalk, Mary Patricia; Talbot, H. Keipp; Treanor, John J.; Belongia, Edward A.; Murthy, Kempapura; Jackson, Lisa A.; Petrie, Joshua G.; Zimmerman, Richard K.; Griffin, Marie R.; McLean, Huong Q.; Fry, Alicia M.
BACKGROUND: Few observational studies have evaluated the relative effectiveness of live attenuated (LAIV) and inactivated (IIV) influenza vaccines against medically attended laboratory-confirmed influenza. METHODS: We analyzed US Influenza Vaccine Effectiveness Network data from participants aged 2 to 17 years during 4 seasons (2010–2011 through 2013–2014) to compare relative effectiveness of LAIV and IIV against influenza-associated illness. Vaccine receipt was confirmed via provider/electronic medical records or immunization registry. We calculated the ratio (odds) of influenza-positive to influenza-negative participants among those age-appropriately vaccinated with either LAIV or IIV for the corresponding season. We examined relative effectiveness of LAIV and IIV by using adjusted odds ratios (ORs) and 95% confidence intervals (CIs) from logistic regression. RESULTS: Of 6819 participants aged 2 to 17 years, 2703 were age-appropriately vaccinated with LAIV (n = 637) or IIV (n = 2066). Odds of influenza were similar for LAIV and IIV recipients during 3 seasons (2010–2011 through 2012–2013). In 2013–2014, odds of influenza were significantly higher among LAIV recipients compared with IIV recipients 2 to 8 years old (OR 5.36; 95% CI, 2.37 to 12.13). Participants vaccinated with LAIV or IIV had similar odds of illness associated with influenza A/H3N2 or B. LAIV recipients had greater odds of illness due to influenza A/H1N1pdm09 in 2010–2011 and 2013–2014. CONCLUSIONS: We observed lower effectiveness of LAIV compared with IIV against influenza A/H1N1pdm09 but not A(H3N2) or B among children and adolescents, suggesting poor performance related to the LAIV A/H1N1pdm09 viral construct. PMID:26738884
Yamin, Dan; Gavious, Arieh; Solnik, Eyal; Davidovitch, Nadav; Balicer, Ran D; Galvani, Alison P; Pliskin, Joseph S
Influenza vaccination is the primary approach to prevent influenza annually. WHO/CDC recommendations prioritize vaccinations mainly on the basis of age and co-morbidities, but have never considered influenza infection history of individuals for vaccination targeting. We evaluated such influenza vaccination policies through small-world contact networks simulations. Further, to verify our findings we analyzed, independently, large-scale empirical data of influenza diagnosis from the two largest Health Maintenance Organizations in Israel, together covering more than 74% of the Israeli population. These longitudinal individual-level data include about nine million cases of influenza diagnosed over a decade. Through contact network epidemiology simulations, we found that individuals previously infected with influenza have a disproportionate probability of being highly connected within networks and transmitting to others. Therefore, we showed that prioritizing those previously infected for vaccination would be more effective than a random vaccination policy in reducing infection. The effectiveness of such a policy is robust over a range of epidemiological assumptions, including cross-reactivity between influenza strains conferring partial protection as high as 55%. Empirically, our analysis of the medical records confirms that in every age group, case definition for influenza, clinical diagnosis, and year tested, patients infected in the year prior had a substantially higher risk of becoming infected in the subsequent year. Accordingly, considering individual infection history in targeting and promoting influenza vaccination is predicted to be a highly effective supplement to the current policy. Our approach can also be generalized for other infectious disease, computer viruses, or ecological networks.
Yamin, Dan; Gavious, Arieh; Solnik, Eyal; Davidovitch, Nadav; Balicer, Ran D.; Galvani, Alison P.; Pliskin, Joseph S.
Influenza vaccination is the primary approach to prevent influenza annually. WHO/CDC recommendations prioritize vaccinations mainly on the basis of age and co-morbidities, but have never considered influenza infection history of individuals for vaccination targeting. We evaluated such influenza vaccination policies through small-world contact networks simulations. Further, to verify our findings we analyzed, independently, large-scale empirical data of influenza diagnosis from the two largest Health Maintenance Organizations in Israel, together covering more than 74% of the Israeli population. These longitudinal individual-level data include about nine million cases of influenza diagnosed over a decade. Through contact network epidemiology simulations, we found that individuals previously infected with influenza have a disproportionate probability of being highly connected within networks and transmitting to others. Therefore, we showed that prioritizing those previously infected for vaccination would be more effective than a random vaccination policy in reducing infection. The effectiveness of such a policy is robust over a range of epidemiological assumptions, including cross-reactivity between influenza strains conferring partial protection as high as 55%. Empirically, our analysis of the medical records confirms that in every age group, case definition for influenza, clinical diagnosis, and year tested, patients infected in the year prior had a substantially higher risk of becoming infected in the subsequent year. Accordingly, considering individual infection history in targeting and promoting influenza vaccination is predicted to be a highly effective supplement to the current policy. Our approach can also be generalized for other infectious disease, computer viruses, or ecological networks. PMID:24851863
Schmid, Philipp; Rauber, Dorothee; Betsch, Cornelia; Lidolt, Gianni; Denker, Marie-Luisa
Background Influenza vaccine hesitancy is a significant threat to global efforts to reduce the burden of seasonal and pandemic influenza. Potential barriers of influenza vaccination need to be identified to inform interventions to raise awareness, influenza vaccine acceptance and uptake. Objective This review aims to (1) identify relevant studies and extract individual barriers of seasonal and pandemic influenza vaccination for risk groups and the general public; and (2) map knowledge gaps in understanding influenza vaccine hesitancy to derive directions for further research and inform interventions in this area. Methods Thirteen databases covering the areas of Medicine, Bioscience, Psychology, Sociology and Public Health were searched for peer-reviewed articles published between the years 2005 and 2016. Following the PRISMA approach, 470 articles were selected and analyzed for significant barriers to influenza vaccine uptake or intention. The barriers for different risk groups and flu types were clustered according to a conceptual framework based on the Theory of Planned Behavior and discussed using the 4C model of reasons for non-vaccination. Results Most studies were conducted in the American and European region. Health care personnel (HCP) and the general public were the most studied populations, while parental decisions for children at high risk were under-represented. This study also identifies understudied concepts. A lack of confidence, inconvenience, calculation and complacency were identified to different extents as barriers to influenza vaccine uptake in risk groups. Conclusion Many different psychological, contextual, sociodemographic and physical barriers that are specific to certain risk groups were identified. While most sociodemographic and physical variables may be significantly related to influenza vaccine hesitancy, they cannot be used to explain its emergence or intensity. Psychological determinants were meaningfully related to uptake and should
Satman, Ilhan; Akalin, Sema; Cakir, Bekir; Altinel, Serdar
We aimed to examine the effect of increased physician awareness on the rate and determinants of influenza and pneumococcal vaccinations in diabetic patients. Diabetic patients (n = 5682, mean [SD] age: 57.3 [11.6] years, 57% female) were enrolled by 44 physicians between Sept 2010 and Jan 2011. The physicians were initially questioned regarding vaccination practices, and then, they attended a training program. During the last five years, the physicians recommended influenza and pneumococcal vaccinations to 87.9% and 83.4% of the patients, respectively; however; only 27% of the patients received the influenza and 9.8% received the pneumococcal vaccines. One year after the training, the vaccination rates increased to 63.3% and 40.7%, respectively. The logistic regression models revealed that variables which increased the likelihood of having been vaccinated against influenza were: longer duration of diabetes, presence of hyperlipidemia and more use of concomitant medications whereas more use of anti-hyperglycemic medications was associated with increased odds of vaccination. On the other hand, older age, longer duration of diabetes and presence of a cardiovascular disease were variables which decreased the likelihood of having been vaccinated against pneumococcal disease during the past five years. However, during the study period, variables which decreased the odds of having been vaccinated included: older age and anti-hyperglycemic medications for influenza, and presence of hyperlipidemia and a family history of hypertension for pneumococcal disease. While variables which increased the likelihood of vaccination in the same period were: increased number of co-morbidities for influenza, and family history of diabetes for pneumococcal disease. We conclude that increased awareness of physicians may help improve vaccination rates against influenza and pneumococcal disease. However, diabetic patients with more severe health conditions are less likely to having been
Goodman, Kenneth; Mossad, Sherif B.; Taksler, Glen B.; Emery, Jonathan; Schramm, Sarah; Rothberg, Michael B.
Objective Despite influenza vaccination being an integral part of prenatal care, vaccination rates remain low. We evaluated the impact of pre-visit video education on patients' vaccination health beliefs and vaccination rate. Study design From November 2013-January 2014, unvaccinated patients seen for routine prenatal care were randomized to pre-visit vaccination video education or control. Pre and post video health beliefs were assessed on a 5-point scale and unvaccinated participants were subsequently interviewed by phone. Results In 105 randomized participants, intervention positively influenced health beliefs as demonstrated by differences in mean pre- vs. post scores for intervention vs. control: vaccination may harm mother (difference =-0.05, p=0.009) and baby (difference=-0.44, p=0.015), and vaccination can protect mother (difference=0.49, p=0.003) and baby (difference=0.59, p=0.001). Vaccination rates were 28% intervention and 25% control (p=0.70). Provider recommendation was associated with vaccination (47% if recommended vs.12% if not, p<.001). Phone interviews revealed susceptibility to influenza and vaccine safety as primary reasons for remaining unvaccinated Conclusions Video education positively influenced vaccination health beliefs without impacting vaccination rates. Physician's recommendation was strongly associated with participant's decision to become and may be most effective when emphasizing influenza vaccination's protective impact on the newborn. PMID:26775454
This study provides information regarding vaccine research and the epidemiology of influenza virus in neglected hosts (horses and dogs). Equine influenza virus (EIV) causes a highly contagious disease in horses and other equids, and outbreaks have occurred worldwide. EIV has resulted in costly damage to the horse industry and has the ability of cross the host species barrier from horses to dogs. Canine influenza is a virus of equine or avian origin and infects companion animals that live in close contact with humans; this results in possible exposure to the seasonal epizootic influenza virus. There have been case reports of genetic reassortment between human and canine influenza viruses, which results in high virulence and the ability of transmission to ferrets. This emphasizes the need for vaccine research on neglected hosts to update knowledge on current strains and to advance technology for controlling influenza outbreaks for public health. PMID:27489801
Na, Woonsung; Yeom, Minjoo; Yuk, Huijoon; Moon, Hyoungjoon; Kang, Bokyu; Song, Daesub
This study provides information regarding vaccine research and the epidemiology of influenza virus in neglected hosts (horses and dogs). Equine influenza virus (EIV) causes a highly contagious disease in horses and other equids, and outbreaks have occurred worldwide. EIV has resulted in costly damage to the horse industry and has the ability of cross the host species barrier from horses to dogs. Canine influenza is a virus of equine or avian origin and infects companion animals that live in close contact with humans; this results in possible exposure to the seasonal epizootic influenza virus. There have been case reports of genetic reassortment between human and canine influenza viruses, which results in high virulence and the ability of transmission to ferrets. This emphasizes the need for vaccine research on neglected hosts to update knowledge on current strains and to advance technology for controlling influenza outbreaks for public health.
Herbinger, Karl-Heinz; von Sonnenburg, Frank; Nothdurft, Hans Dieter; Perona, Pamela; Borkowski, Astrid; Fragapane, Elena; Nicolay, Uwe; Clemens, Ralf
An investigational tetravalent vaccine combining pre-pandemic, MF59®-adjuvanted A/H5N1 vaccine with non-adjuvanted, trivalent, seasonal influenza vaccine has been developed, which has the potential to be used for pre-pandemic priming and to improve levels of compliance and coverage. It is important to determine whether the safety and immunogenicity of the combination vaccine is equivalent to that of the two separate vaccines when administered concomitantly. Healthy adults (n=601) were randomly assigned to three vaccination groups to receive either: (1) tetravalent vaccine and placebo concomitantly (in separate arms) on Day 1, followed by A/H5N1 vaccine on Day 22; (2) A/H5N1 vaccine and placebo concomitantly on Day 1, followed by tetravalent vaccine on Day 22; or (3) A/H5N1 and seasonal vaccines concomitantly on Day 1, followed by A/H5N1 vaccine on Day 22. Antibody responses were measured using single radial hemolysis (SRH), haemagglutination inhibition (HI), and microneutralization (MN) assays on Days 1, 22, and 43. Solicited adverse reactions were recorded for seven days after vaccination. Spontaneous adverse events were recorded throughout the study. The tetravalent vaccine elicited antibody titers equivalent to those for separate A/H5N1 and seasonal vaccines, and sufficient to meet the European licensure criteria against A/H5N1 and all three seasonal strains. Local and systemic reactions were mainly mild to moderate. No vaccine-related serious adverse events occurred. These findings demonstrate that MF59-adjuvanted A/H5N1 and seasonal influenza vaccines had an acceptable safety profile and could be effectively administered as a tetravalent formulation, supporting the possibility of integrating pre-pandemic priming into seasonal influenza vaccination programs.
He, Biao; Chang, Haiyan; Liu, Zhihua; Huang, Chaoyang; Liu, Xueying; Zheng, Dan; Fang, Fang; Sun, Bing; Chen, Ze
Vaccination is the best measure to prevent influenza pandemics. Here, we studied the protective effect against heterologous influenza viruses, including A/reassortant/NYMC X-179A (pH1N1), A/Chicken/Henan/12/2004 (H5N1), A/Chicken/Jiangsu/7/2002 (H9N2) and A/Guizhou/54/89×A/PR/8/34 (A/Guizhou-X) (H3N2), in mice first vaccinated with a DNA vaccine of haemagglutinin (HA) or neuraminidase (NA) of A/PR/8/34 (PR8) and then infected with the homologous virus. We showed that PR8 HA or NA vaccination both protected mice against a lethal dose of the homologous virus; PR8 HA or NA DNA vaccination and then PR8 infection in mice offered poor or excellent protection, respectively, against a second, heterologous influenza virus challenge. In addition, before the second heterologous influenza infection, the highest antibody level against nucleoprotein (NP) and matrix (M1 and M2) proteins was found in the PR8 NA-vaccinated and PR8-infected group. The level of induced cellular immunity against NP and M1 showed a trend consistent with that seen in antibody levels. However, PR8 HA+NA vaccination and then PR8 infection resulted in limited protection against heterologous influenza virus challenge. Results of the present study demonstrated that infection of the homologous influenza virus in mice already immunized with a NA vaccine could provide excellent protection against subsequent infection of a heterologous influenza virus. These findings suggested that NA, a major antigen of influenza virus, could be an important candidate antigen for universal influenza vaccines.
Spinner, Justin L.; Oberoi, Hardeep S.; Yorgensen, Yvonne M.; Poirier, Danielle S.; Burkhart, David J.; Plante, Martin; Evans, Jay T.
Influenza is a vaccine-preventable contagious respiratory illness caused by influenza (flu) viruses which can lead to hospitalization and sometimes even death. Current flu vaccines delivered intramuscularly (IM) or intradermally (ID) are less effective at eliciting protective mucosal immune responses and vaccines delivered intranasally (IN) possess potential safety concerns. Sublingual (SL) vaccination is a promising alternative route for vaccine delivery which has been indicated as safe and effective at inducing protective immune responses in both systemic and mucosal compartments. We evaluated the efficacy of methylglycol chitosan (MGC) and a synthetic toll-like receptor 4 agonist (CRX-601), alone or in combination, for improving systemic and mucosal immune responses to a monovalent detergent-split flu virus vaccine delivered SL. SL vaccination of mice with split-flu vaccine formulated with either MGC or CRX-601 resulted in specific serum IgG and mucosal IgA titers that were significantly greater than titers from non-adjuvanted vaccination and equivalent to or greater than titers in mice vaccinated IM. Our results demonstrate that SL vaccination utilizing MGC or CRX-601 as adjuvants is a viable alternative route of vaccination for flu which can elicit systemic immune responses equivalent to or greater than IM vaccination with the added benefit of stimulating a robust specific mucosal immune response. PMID:26392012
Spinner, Justin L; Oberoi, Hardeep S; Yorgensen, Yvonne M; Poirier, Danielle S; Burkhart, David J; Plante, Martin; Evans, Jay T
Influenza is a vaccine-preventable contagious respiratory illness caused by influenza (flu) viruses which can lead to hospitalization and sometimes even death. Current flu vaccines delivered intramuscularly (IM) or intradermally (ID) are less effective at eliciting protective mucosal immune responses and vaccines delivered intranasally (IN) possess potential safety concerns. Sublingual (SL) vaccination is a promising alternative route for vaccine delivery which has been indicated as safe and effective at inducing protective immune responses in both systemic and mucosal compartments. We evaluated the efficacy of methylglycol chitosan (MGC) and a synthetic toll-like receptor 4 agonist (CRX-601), alone or in combination, for improving systemic and mucosal immune responses to a monovalent detergent-split flu virus vaccine delivered SL. SL vaccination of mice with split-flu vaccine formulated with either MGC or CRX-601 resulted in specific serum IgG and mucosal IgA titers that were significantly greater than titers from non-adjuvanted vaccination and equivalent to or greater than titers in mice vaccinated IM. Our results demonstrate that SL vaccination utilizing MGC or CRX-601 as adjuvants is a viable alternative route of vaccination for flu which can elicit systemic immune responses equivalent to or greater than IM vaccination with the added benefit of stimulating a robust specific mucosal immune response.
Zhang, Xu-Sheng; Pebody, Richard; De Angelis, Daniela; White, Peter J.; Charlett, Andre; McCauley, John W.
Background One pathway through which pandemic influenza strains might emerge is reassortment from coinfection of different influenza A viruses. Seasonal influenza vaccines are designed to target the circulating strains, which intuitively decreases the prevalence of coinfection and the chance of pandemic emergence due to reassortment. However, individual-based analyses on 2009 pandemic influenza show that the previous seasonal vaccination may increase the risk of pandemic A(H1N1) pdm09 infection. In view of pandemic influenza preparedness, it is essential to understand the overall effect of seasonal vaccination on pandemic emergence via reassortment. Methods and Findings In a previous study we applied a population dynamics approach to investigate the effect of infection-induced cross-immunity on reducing such a pandemic risk. Here the model was extended by incorporating vaccination for seasonal influenza to assess its potential role on the pandemic emergence via reassortment and its effect in protecting humans if a pandemic does emerge. The vaccination is assumed to protect against the target strains but only partially against other strains. We find that a universal seasonal vaccine that provides full-spectrum cross-immunity substantially reduces the opportunity of pandemic emergence. However, our results show that such effectiveness depends on the strength of infection-induced cross-immunity against any novel reassortant strain. If it is weak, the vaccine that induces cross-immunity strongly against non-target resident strains but weakly against novel reassortant strains, can further depress the pandemic emergence; if it is very strong, the same kind of vaccine increases the probability of pandemic emergence. Conclusions Two types of vaccines are available: inactivated and live attenuated, only live attenuated vaccines can induce heterosubtypic immunity. Current vaccines are effective in controlling circulating strains; they cannot always help restrain pandemic
Martínez-Baz, Iván; Navascués, Ana; Pozo, Francisco; Chamorro, Judith; Albeniz, Esther; Casado, Itziar; Reina, Gabriel; Cenoz, Manuel García; Ezpeleta, Carmen; Castilla, Jesús
Studies that have evaluated the influenza vaccine effectiveness (VE) to prevent laboratory-confirmed influenza B cases are uncommon, and few have analyzed the effect in preventing hospitalized cases. We have evaluated the influenza VE in preventing outpatient and hospitalized cases with laboratory-confirmed influenza in the 2012–2013 season, which was dominated by a vaccine-matched influenza B virus. In the population covered by the Navarra Health Service, all hospitalized patients with influenza-like illness (ILI) and all ILI patients attended by a sentinel network of general practitioners were swabbed for influenza testing, and all were included in a test-negative case-control analysis. VE was calculated as (1-odds ratio)×100. Among 744 patients tested, 382 (51%) were positive for influenza virus: 70% for influenza B, 24% for A(H1N1)pdm09, and 5% for A(H3N2). The overall estimate of VE in preventing laboratory-confirmed influenza was 63% (95% confidence interval (CI): 34 to 79), 55% (1 to 80) in outpatients and 74% (33 to 90) in hospitalized patients. The VE was 70% (41 to 85) against influenza B and 43% (−45 to 78) against influenza A. The VE against virus B was 87% (52 to 96) in hospitalized patients and 56% in outpatients (−5 to 81). Adjusted comparison of vaccination status between inpatient and outpatient cases with influenza B did not show statistically significant differences (odds ratio: 1.13; p = 0.878). These results suggest a high protective effect of the vaccine in the 2012–2013 season, with no differences found for the effect between outpatient and hospitalized cases. PMID:25996366
Kunze, Ursula; Kunze, Michael
This paper describes a paradoxical situation in Austria. The vaccination rate against tick-borne encephalitis (TBE) in the general population is 82%, which is the highest worldwide, whereas the vaccination rate against influenza is about 8% and is among the lowest worldwide. A high awareness of TBE among the Austrian population achieved by an annual social marketing programme and the wide use of effective and well-tolerated vaccines have led to a successful containment of that disease. The vaccination coverage increased from 6% in 1980 to 82% in 2013 and exceeds 90% in some high-risk areas. This has led to a steady decline in the number of TBE cases from several hundred cases to 50 to 100 cases per year. The situation in regard to influenza vaccination is the opposite. Although Austria has issued one of the most extensive recommendations for influenza vaccination worldwide, the vaccination rate of the general population is extremely low. The possible reasons for the failure in the implementation of recommendations are ignorance, lack of social marketing and the predominance of a distinct discordance within the health system in general, and the Austrian medical fraternity in particular.
de Perio, Marie A.; Wiegand, Douglas M.; Brueck, Scott E.
Background: Influenza can spread among students, teachers, and staff in school settings. Vaccination is the most effective method to prevent influenza. We determined 2012-2013 influenza vaccination coverage among school employees, assessed knowledge and attitudes regarding the vaccine, and determined factors associated with vaccine receipt.…
... Influenza Vaccination Week, 2010 8615 Proclamation 8615 Presidential Documents Proclamations Proclamation 8615 of December 7, 2010 Proc. 8615 National Influenza Vaccination Week, 2010By the President of the... National Influenza Vaccination Week, we remind all Americans that the flu vaccine is safe and effective...
Swayne, D E; Suarez, D L
Until recently, most vaccines against avian influenza were based on oil-emulsified inactivated low- or high-pathogenicity viruses. Now, recombinant fowl pox and avian paramyxovirus type 1 vaccines with avian influenza H5 gene inserts (+ or - N1 gene insert) are available and licensed. New technologies might overcome existing limitations to make available vaccines that can be grown in tissue culture systems for more rapid production; provide optimized protection, as a result of closer genetic relations to field viruses; allow mass administration by aerosol, in drinking-water or in ovo; and allow easier strategies for identifying infected birds within vaccinated populations (DIVA). The technologies include avian influenza viruses with partial gene deletions, avian influenza-Newcastle disease virus chimeras, vectored vaccines such as adenoviruses and Marek's disease virus, and subunit vaccines. These new methods should be licensed only after their purity, safety, efficacy and potency against avian influenza viruses have been demonstrated, and, for live vectored vaccines, restriction of viral transmission to unvaccinated birds. Use of vaccines in countries affected by highly pathogenic avian influenza will not only protect poultry but will provide additional safety for consumers. Experimental studies have shown that birds vaccinated against avian influenza have no virus in meat and minimal amounts in eggs after HPAI virus challenge, and that replication and shedding from their respiratory and alimentary tracts is greatly reduced.
Castro, Breno Augusto Campos de; Pereira, Juliana Milagres Macedo; Meyer, Renata Leal Bregunci; Trindade, Fernanda Marques; Pedrosa, Moises Salgado; Piancastelli, André Costa Cruz
The etiology of pityriasis lichenoides is unknown. One of the accepted theories admits that PL is an inflammatory response to extrinsic antigens such as infectious agents, drugs and vaccines. In recent medical literature, only the MMR vaccine (Measles, Mumps and Rubella) was associated with the occurrence of this disease. We present a case of a male, 12 year old healthy patient who, five days after Influenza vaccination, developed erythematous papules on the trunk, abdomen and limbs, some with adherent crusts and associated systemic symptoms. This case report is notable for describing the first case of pityriasis lichenoides et varioliformis acuta associated with the vaccine against Influenza.
Du, Xiaogang; Wang, Junpeng; Niu, Xinli; Smith, Donald; Wu, Dayong; Meydani, Simin Nikbin
Current vaccines for influenza do not fully protect the aged against influenza infection. Although wolfberry (goji berry) has been shown to improve immune response, including enhanced antibody production, after vaccination in the aged, it is not known if this effect would translate to better protection after influenza infection, nor is its underlying mechanism well understood. To address these issues, we conducted a study using a 2 × 2 design in which aged male mice (20-22 mo) were fed a control or a 5% wolfberry diet for 30 d, then immunized with an influenza vaccine or saline (control) on days 31 and 52 of the dietary intervention, and finally challenged with influenza A/Puerto Rico/8/34 virus. Mice fed wolfberry had higher influenza antibody titers and improved symptoms (less postinfection weight loss) compared with the mice treated by vaccine alone. Furthermore, an in vitro mechanistic study showed that wolfberry supplementation enhanced maturation and activity of antigen-presenting dendritic cells (DCs) in aged mice, as indicated by phenotypic change in expression of DC activation markers major histocompatibility complex class II, cluster of differentiation (CD) 40, CD80, and CD86, and functional change in DC production of cytokines interleukin-12 and tumor necrosis factor-α as well as DC endocytosis. Also, adoptive transfer of wolfberry-treated bone marrow DCs (loaded with ovalbumin(323-339)-peptide) promoted antigen-specific T cell proliferation as well as interleukin-4 and interferon-γ production in CD4(+) T cells. In summary, our data indicate that dietary wolfberry enhances the efficacy of influenza vaccination, resulting in better host protection to prevent subsequent influenza infection; this effect may be partly attributed to improved DC function.
Mistilis, Matthew J; Bommarius, Andreas S; Prausnitz, Mark R
The goal of this study is to develop thermostable microneedle patch formulations for influenza vaccine that can be partially or completely removed from the cold chain. During vaccine drying associated with microneedle patch manufacturing, ammonium acetate and 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES) buffer salts stabilized influenza vaccine, surfactants had little effect during drying, drying temperature had weak effects on vaccine stability, and drying on polydimethylsiloxane (PDMS) led to increased stability compared with drying on stainless steel. A number of excipients, mostly polysaccharides and some amino acids, further stabilized the influenza vaccine during drying. Over longer time scales of storage, combinations of stabilizers preserved the most vaccine activity. Finally, dissolving microneedle patches formulated with arginine and calcium heptagluconate had no significant activity loss for all three strains of seasonal influenza vaccine during storage at room temperature for 6 months. We conclude that appropriately formulated microneedle patches can exhibit remarkable thermostability that could enable storage and distribution of influenza vaccine outside the cold chain.
Travers, Jasmine L; Stone, Patricia W; Bjarnadottir, Ragnhildur I; Pogorzelska-Maziarz, Monika; Castle, Nicholas G; Herzig, Carolyn T A
Influenza vaccination remains the cornerstone of influenza prevention, yet national goals for nursing home residents and staff vaccination have not been met. Few studies have examined associations between facility and resident characteristics; employee processes, such as staff vaccination policies; and resident influenza vaccination. In this national survey of nursing homes, employee processes were not associated with resident influenza vaccination; however, various facility and resident characteristics were.
Plantet, Claire; Sanchez, Stéphane; Cohen, Nadia; Denormandie, Philippe; Dinh, Aurélien
Influenza epidemics in nursing homes can lead to serious complications with a high level of lethality. It has been shown that an active policy of awareness campaigns with obligatory information materials and easy access to influenza immunisation increases the rate of vaccination coverage.
Novati, R; Nebiolo, P E; Galotto, C; Mastaglia, M; Manes, M
A fifty-three years old surgeon had acute renal failure consisting with acute tubulo-interstizial nephropaty twelve days after influenza vaccination; he was on statin therapy since one month. He was given steroidal therapy and fully recovered two weeks apart. This is the fourth case report of acute renal failure after influenza vaccination in patients on statins therapy. The case we describe could account for a underestimated, even if very rare, phenomenon.
Cox, Manon M. J.
Pandemic influenza has become a high priority item for all public health authorities. An influenza pandemic is believed to be imminent, and scientists agree that it will be a matter of when, where, and what will be the causative agent. Recently, most attention has been directed to human cases of avian influenza caused by a H5N1 avian influenza virus. An effective vaccine will be needed to substantially reduce the impact of an influenza pandemic. Current influenza vaccine manufacturing technology is not adequate to support vaccine production in the event of an avian influenza outbreak, and it has now become clear that new innovative production technology is required. Antiviral drugs, on the other hand, can play a very important role in slowing the disease spread but are in short supply and resistance has been a major issue. Here, we provide an update on the status of pandemic vaccine development and antiviral drugs. Finally, we conclude with some proposed areas of focus in pandemic vaccine preparedness. PMID:17132338
Bödeker, B; Wichmann, O; Mertens, B; Seefeld, L; Pott, E
Residents and staff of nursing homes are important target groups for influenza vaccination in Germany. The aim of this study was to gain the first insights into whether nursing homes organize activities with respect to vaccination against influenza and whether there is a demand for further information. In the context of the national influenza immunization campaign-which is jointly carried out by the Robert Koch Institute (RKI) and the Federal Centre for Health Education (BZgA) on an annual basis-influenza information kits were sent to the management of 10,700 nursing homes in September 2013. Along with the information material, the institutions also received a questionnaire to which they were able to respond via mail, fax, or online. Data from 988 homes were included in the analysis. The majority of institutions informed both residents (88.9 %) and nursing staff (81.2 %) about influenza vaccination. However, only 64.7 % of nursing homes carried out specific immunization activities for their residents and only half (49.3 %) offered a flu shot to their staff. When asked why the institutions do not provide influenza-specific information and vaccination to their staff, the majority had the opinion that this is the responsibility of each individual's general practitioner. Overall, only 4.9 % of nursing homes assessed influenza vaccination coverage among their staff annually. A third of all surveyed institutions (33.6 %) expressed a demand for additional influenza vaccine-related information. In conclusion, improved health education is needed to raise awareness about the importance of influenza vaccination among residents and employees of nursing homes in Germany so as to prevent influenza-associated morbidity and mortality in this risk group.
Romagosa, Anna; Allerson, Matt; Gramer, Marie; Joo, Han Soo; Deen, John; Detmer, Susan; Torremorell, Montserrat
Limited information is available on the transmission and spread of influenza virus in pig populations with differing immune statuses. In this study we assessed differences in transmission patterns and quantified the spread of a triple reassortant H1N1 influenza virus in naïve and vaccinated pig populations by estimating the reproduction ratio (R) of infection (i.e. the number of secondary infections caused by an infectious individual) using a deterministic Susceptible-Infectious-Recovered (SIR) model, fitted on experimental data. One hundred and ten pigs were distributed in ten isolated rooms as follows: (i) non-vaccinated (NV), (ii) vaccinated with a heterologous vaccine (HE), and (iii) vaccinated with a homologous inactivated vaccine (HO). The study was run with multiple replicates and for each replicate, an infected non-vaccinated pig was placed with 10 contact pigs for two weeks and transmission of influenza evaluated daily by analyzing individual nasal swabs by RT-PCR. A statistically significant difference between R estimates was observed between vaccinated and non-vaccinated pigs (p < 0.05). A statistically significant reduction in transmission was observed in the vaccinated groups where R (95%CI) was 1 (0.39-2.09) and 0 for the HE and the HO groups respectively, compared to an Ro value of 10.66 (6.57-16.46) in NV pigs (p < 0.05). Transmission in the HE group was delayed and variable when compared to the NV group and transmission could not be detected in the HO group. Results from this study indicate that influenza vaccines can be used to decrease susceptibility to influenza infection and decrease influenza transmission.
Jiang, Jiu; Fisher, Erin M; Hensley, Scott E; Lustigman, Sara; Murasko, Donna M; Shen, Hao
Influenza is one of the most common infectious diseases endangering the health of humans, especially young children and the elderly. Although vaccination is the most effective means of protection against influenza, frequent mutations in viral surface antigens, low protective efficacy of the influenza vaccine in the elderly, slow production process and the potential of vaccine supply shortage during a pandemic are significant limitations of current vaccines. Adjuvants have been used to enhance the efficacy of a variety of vaccines; however, no adjuvant is included in current influenza vaccines approved in the United States. In this study, we found that a novel adjuvant, rOv-ASP-1, co-administrated with inactivated influenza vaccine using an aqueous formulation, substantially improved the influenza-specific antibody response and protection against lethal infection in a mouse model. rOv-ASP-1 enhanced the magnitude of the specific antibody response after immunization with low doses of influenza vaccine, allowing antigen-sparring by 10-fold. The rOv-ASP-1 formulated vaccine induced a more rapid response and a stronger Th1-associated antibody response compared to vaccine alone and to the vaccine formulated with the adjuvant alum. Importantly, rOv-ASP-1 significantly enhanced cross-reactive antibody responses and protection against challenge with an antigenically distinct strain. These results demonstrate that rOv-ASP-1 is an effective adjuvant that: (1) accelerates and enhances the specific antibody response induced by influenza vaccine; (2) allows for antigen sparing; and (3) augments a Th1-biased and cross-reactive antibody response that confers protection against an antigenically distinct strain.
Grødeland, Gunnveig; Bogen, Bjarne
There are two major limitations to vaccine preparedness in the event of devastating influenza pandemics: the time needed to generate a vaccine and rapid generation of sufficient amounts. DNA vaccination could represent a solution to these problems, but efficacy needs to be enhanced. In a separate line of research, it has been established that targeting of vaccine molecules to antigen-presenting cells enhances immune responses. We have combined the two principles by constructing DNA vaccines that encode bivalent fusion proteins; these target hemagglutinin to MHC class II molecules on antigen-presenting cells. Such DNA vaccines rapidly induce hemagglutinin-specific antibodies and T cell responses in immunized mice. Responses are long-lasting and protect mice against challenge with influenza virus. In a pandemic situation, targeted DNA vaccines could be produced and tested within a month. The novel DNA vaccines could represent a solution to pandemic preparedness in the advent of novel influenza pandemics.
Zverev, V V; Katlinskiĭ, A V; Kostinov, M P; Zhirova, S N; Erofeeva, M K; Stukova, M A; Korovkin, S A; Mel'nikov, S Ia; Semchenko, A V; Mironov, A N
Scientic-production association "Microgen" has finished 1st phase of clinical trials of candidate vaccines against avian influenza in order to assess their reactogenicity, safety, and immunogenicity. Two vaccines constructed from NIBRG-14 vaccine strain [A/Vietnam/1 194/2004 (H5N1)], obtained from World Health Organization, were studied: "OrniFlu" (inactivated subunit influenza vaccine adsorbed on aluminium hydroxide) and inactivated polymer-subunit influenza vaccine with polyoxydonium (IPSIV). Clinical trial of the vaccines with different quantity of antigen (15, 30, and 45 mcg of H5N1 virus hemagglutinin) was carried out in Influenza Research Institute (St. Petersburg) and in Mechnikov Research Institute of Vaccines and Sera (Moscow). Analysis of results allowed to conclude that both vaccines were safe, well tolerated and characterized by low reactogenicity. Two-doses vaccination schedule was needed to meet required seroconversion and seroprotection rates (> or =1:40 in > or =70% of vaccinated volunteers). "Orni-Flu" vaccine containing 15 mcg of hemagglutinin and optimal quantity of aluminium hydroxide (0.5 mg) in one dose as well as IPSIV containing 45 mcg of hemagglutinin and 0.75 mg of polyoxydonium in one dose were most immunogenic after 2 doses - seroprotection rates in microneutralization assay were 72.2% and 77.0% respectively. Marked influence of aluminium hydroxide content on immunogenicity of the "OrniFlu" vaccine was confirmed in the study. Optimal quantity of adjuvant was 0.5 mg per dose. According to basic concept of vaccine development, preference is given to vaccine that under minimal quantity of antigen induces sufficient specific immune response and is safe in volunteers. "OrniFlu" vaccine containing 15 mcg of H5N1 virus hemagglutinin and optimal quantity of aluminium hydroxide (0.5 mg) corresponded to these requirements that allowed researchers to recommend it for clinical trials of 2nd phase.
Gamoh, Koichiro; Nakamura, Shigeyuki
The basic countermeasures used to control highly pathogenic avian influenza (HPAI) are early detection procedures and the culling of affected chickens. However, if successive HPAI outbreaks occur, the vaccination may be an option for controlling HPAI. Therefore, avian influenza (AI) vaccines are stocked by the Japanese government. By contrast, equine influenza (EI) vaccine is an effective tool for preventing or controlling EI. Because antigenic drifts affect the efficacy of AI and EI vaccines, the vaccine strains should be updated rapidly. However, the development and registration of veterinary vaccines usually takes several years. In response to this issue, the Ministry of Agriculture, Forestry, and Fisheries (MAFF) established a system that allows AI and EI vaccine strains to be updated rapidly. National Veterinary Assay Laboratory, MAFF, established a vaccine strains selection committee for veterinary influenza vaccine. The main agendas involve determining whether the current vaccine strains need to be updated and selecting the most appropriate vaccine strains. The committee concluded that A/duck/Hokkaido/Vac-3/2007(H5N1) was added to the strains of stockpiled AI vaccines and that the EI vaccine strains did not need to be changed, but that the clade 2 viruses of the Florida sub-lineage strain, A/equine/Yokohama/aq13/2010(H3N8) was added to the EI vaccine strain.
Macdonald, Laura; Cairns, Georgina; Angus, Kathryn; de Andrade, Marisa
The authors conducted a systematic review that aimed to map current practice and identify effective practice in promotional communications for seasonal influenza vaccination in Europe. They identified 22 studies from 7 European countries. Included studies were primarily outcome evaluations of communications promoting vaccination to health care workers and elderly adults. Evidence on communications to improve public acceptance was sparse. A range of communication approaches, methods, materials, and channels were used, frequently in combination. All forms of promotional communications have the potential to increase uptake in health care workers and can also improve uptake among patients. There was promising evidence that mass communication methods, delivered as standalone activities or as one component of a communication mix, can improve uptake in target populations. Education for health care workers and improved service delivery are common adjuncts to promotional communications that were associated with effectiveness. The evidence suggests that personalized communications, combined with improved service delivery, might boost rates of uptake among elderly adults. Future development of good practice could be enhanced by more systematic, theory-based intervention design and more detailed reporting of process and outcome evaluations. Vaccine hesitancy is increasingly prevalent; more policy and research to improve public acceptance should therefore be considered.
Nakaya, Helder I; Wrammert, Jens; Lee, Eva K; Racioppi, Luigi; Marie-Kunze, Stephanie; Haining, W. Nicholas; Means, Anthony R; Kasturi, Sudhir P; Khan, Nooruddin; Li, Gui-Mei; McCausland, Megan; Kanchan, Vibhu; Kokko, Kenneth E; Li, Shuzhao; Elbein, Rivka; Mehta, Aneesh K; Aderem, Alan; Subbarao, Kanta; Ahmed, Rafi; Pulendran, Bali
We used a systems biological approach to study innate and adaptive responses to influenza vaccination in humans, during 3 consecutive influenza seasons. Healthy adults were vaccinated with inactivated (TIV) or live attenuated (LAIV) influenza vaccines. TIV induced greater antibody titers and enhanced numbers of plasmablasts than LAIV. In TIV vaccinees, early molecular signatures correlated with, and accurately predicted, later antibody titers in two independent trials. Interestingly, the expression of Calcium/calmodulin-dependent kinase IV (CamkIV) at day 3 was inversely correlated with later antibody titers. Vaccination of CamkIV −/− mice with TIV induced enhanced antigen-specific antibody titers, demonstrating an unappreciated role for CaMKIV in the regulation of antibody responses. Thus systems approaches can predict immunogenicity, and reveal new mechanistic insights about vaccines. PMID:21743478
Shen, Zhenwei; Lei, Han
Human β-defensin-2 (hBD-2) is an antimicrobial peptide with high activity and broad spectrum activity. hBD-2 expression may be highly elevated by microorganisms and inflammation. We reported that the majority of common vaccines used, including 23-valent pneumococcal polysaccharide vaccine, Haemophilus influenzae type b vaccine and split influenza virus vaccine, could induce the expression of hBD-2 in epithelial cells. Among them, the 23-valent pneumococcal polysaccharide vaccine was effective at a lower concentration (0.5 µg/ml), while Haemophilus influenzae type b vaccine and split influenza virus vaccine were effective at the concentration of 1 µg/ml. However, bacteriostatic experiments revealed that the split influenza virus vaccine was capable of inducing the highest antimicrobial activity. The medium of the 23-valent pneumococcal polysaccharide vaccine treatment group had a higher antimicrobial activity than the medium of the Haemophilus influenzae type b vaccine treatment group. The transcriptional regulator of hBD-2, that is, the NF-κB subunit, had a high level of activity, while the normal epithelial cells showed barely detectable activity, indicating that these vaccines have potential for clinical application.
Li, Chengjun; Bu, Zhigao; Chen, Hualan
H5N1 avian influenza viruses (AIVs) have spread widely to more than 60 countries spanning three continents. To control the disease, vaccination of poultry is implemented in many of the affected countries, especially in those where H5N1 viruses have become enzootic in poultry and wild birds. Recently, considerable progress has been made toward the development of novel avian influenza (AI) vaccines, especially recombinant virus vector vaccines and DNA vaccines. Here, we will discuss the recent advances in vaccine development and use against H5N1 AIV in poultry. Understanding the properties of the available, novel vaccines will allow for the establishment of rational vaccination protocols, which in turn will help the effective control and prevention of H5N1 AI.
Grijalva, Carlos G.; Zhu, Yuwei; Williams, Derek J.; Self, Wesley H.; Ampofo, Krow; Pavia, Andrew T.; Stockmann, Chris R.; McCullers, Jonathan; Arnold, Sandra R.; Wunderink, Richard G.; Anderson, Evan J.; Lindstrom, Stephen; Fry, Alicia M.; Foppa, Ivo M.; Finelli, Lyn; Bramley, Anna M.; Jain, Seema; Griffin, Marie R.; Edwards, Kathryn M.
Importance Few studies have evaluated the relationship between influenza vaccination and pneumonia, a serious complication of influenza infection. Objective Assess the association between influenza vaccination status and hospitalization for community-acquired laboratory-confirmed influenza pneumonia. Design, Setting and Participants The Etiology of Pneumonia in the Community (EPIC) study was a prospective observational multicenter study of hospitalizations for community-acquired pneumonia conducted from January 2010 through June 2012 in four US sites. We used EPIC study data from patients ≥6 months of age with laboratory-confirmed influenza infection and verified vaccination status during the influenza seasons, and excluded patients with recent hospitalization, from chronic care residential facilities, and with severe immunosuppression. Logistic regression was used to calculate odds ratios, comparing the odds of vaccination between influenza-positive (cases) and influenza-negative (controls) pneumonia patients, controlling for demographics, co-morbidities, season, study site and timing of disease onset. Vaccine effectiveness was estimated as (1-odds ratio) × 100%. Exposure Influenza vaccination, verified through record review. Outcome Influenza pneumonia, confirmed by real-time reverse transcription-polymerase chain reaction performed on nasal/oropharyngeal swabs. Results Overall, 2767 patients hospitalized for pneumonia were eligible for the study; 162 (5.9%) were influenza positive. Twenty-eight (17%) of 162 cases with influenza-associated pneumonia and 766 (29%) of 2605 controls with influenza-negative pneumonia had been vaccinated. The adjusted odds ratio of prior influenza vaccination between cases and controls was 0.43 (95% CI 0.28–0.68 [estimated vaccine effectiveness 56.7% (95% CI 31.9–72.5)]). Conclusions and relevance Among children and adults hospitalized with community-acquired pneumonia, those with laboratory confirmed influenza
Swayne, David E
Avian influenza vaccines for poultry are based on hemagglutinin proteins, and protection is specific to the vaccine subtype. Over 113 billion doses have been used between 2002 and 2010 for high pathogenicity avian influenza control. No universal vaccines are currently available. The majority of avian influenza vaccines are inactivated whole influenza viruses that are grown in embryonating eggs, inactivated, emulsified in oil adjuvant systems, and injected into chickens. Live virus-vectored vaccines such as recombinant viruses of fowl pox, Newcastle disease, herpesvirus of turkeys and duck enteritis containing inserts of avian influenza virus hemagglutinin genes have been used on a more limited basis. In studies to evaluate vaccine efficacy and potency, the protocol design and its implementation should address the biosafety level needed for the work, provide information required for approval by Institutional Biosafety and Animal Care Committees, contain information on seed strain selection, provide needed information on animal subjects and their relevant parameters, and address the selection and use of challenge viruses. Various metrics have been used to directly measure vaccine induced protection. These include prevention of death, clinical signs, and lesions; prevention of decreases in egg production and alterations in egg quality; quantification of the reduction in virus replication and shedding from the respiratory tract and gastrointestinal tracts; and prevention of contact transmission in in vivo poultry experiments. In addition, indirect measures of vaccine potency and protection can be developed and validated against the direct measures and include serological assays in vaccinated poultry and assessment of the content of hemagglutinin antigen in the vaccine. These indirect assessments of protection are useful in determining if vaccine batches have a consistent ability to protect. For adequate potency, vaccines should contain 50 mean protective doses of
Norman, James J; Arya, Jaya M; McClain, Maxine A; Frew, Paula M; Meltzer, Martin I; Prausnitz, Mark R
While therapeutic drugs are routinely self-administered by patients, there is little precedent for self-vaccination. Convenient self-vaccination may expand vaccination coverage and reduce administration costs. Microneedle patches are in development for many vaccines, but no reports exist on usability or acceptability. We hypothesized that naïve patients could apply patches and that self-administered patches would improve stated intent to receive an influenza vaccine. We conducted a randomized, repeated measures study with 91 venue-recruited adults. To simulate vaccination, subjects received placebo microneedle patches given three times by self-administration and once by the investigator, as well as an intramuscular injection of saline. Seventy participants inserted patches with thumb pressure alone and the remainder used snap-based devices that closed shut at a certain force. Usability was assessed by skin staining and acceptability was measured with an adaptive-choice analysis. The best usability was seen with the snap device, with users inserting a median value of 93-96% of microneedles over three repetitions. When a self-administered microneedle patch was offered, intent to vaccinate increased from 44% to 65% (CI: 55-74%). The majority of those intending vaccination would prefer to self-vaccinate: 64% (CI: 51-75%). There were no serious adverse events associated with use of microneedle patches. The findings from this initial study indicate that microneedle patches for self-vaccination against influenza are usable and may lead to improved vaccination coverage.
Eichelberger, Maryna; Golding, Hana; Hess, Maureen; Weir, Jerry; Subbarao, Kanta; Luke, Catherine J; Friede, Martin; Wood, David
The goals of the workshop were to identify gaps in our knowledge and abilities to address the unique challenges encountered in the development of vaccines intended to protect against pandemic influenza and to facilitate implementation of a global research agenda to improve efficacy assessment of pandemic influenza vaccines. This workshop included discussions on: (i) current knowledge regarding immune correlates of protection against seasonal influenza; (ii) human immune responses to avian influenza infection and vaccines for novel influenza viruses; (iii) limitations of currently available assays to evaluate vaccine immunogenicity; and (iv) potential insights from animal models for correlates of protection against avian influenza.
Black, Carla L; Yue, Xin; Ball, Sarah W; Donahue, Sara M A; Izrael, David; de Perio, Marie A; Laney, A Scott; Williams, Walter W; Lindley, Megan C; Graitcer, Samuel B; Lu, Peng-Jun; DiSogra, Charles; Devlin, Rebecca; Walker, Deborah K; Greby, Stacie M
The Advisory Committee on Immunization Practices recommends annual influenza vaccination for all health care personnel to reduce influenza-related morbidity and mortality among both health care personnel and their patients (1-4). To estimate influenza vaccination coverage among U.S. health care personnel for the 2015-16 influenza season, CDC conducted an opt-in Internet panel survey of 2,258 health care personnel during March 28-April 14, 2016. Overall, 79.0% of survey participants reported receiving an influenza vaccination during the 2015-16 season, similar to the 77.3% coverage reported for the 2014-15 season (5). Coverage in long-term care settings increased by 5.3 percentage points compared with the previous season. Vaccination coverage continued to be higher among health care personnel working in hospitals (91.2%) and lower among health care personnel working in ambulatory (79.8%) and long-term care settings (69.2%). Coverage continued to be highest among physicians (95.6%) and lowest among assistants and aides (64.1%), and highest overall among health care personnel who were required by their employer to be vaccinated (96.5%). Among health care personnel working in settings where vaccination was neither required, promoted, nor offered onsite, vaccination coverage continued to be low (44.9%). An increased percentage of health care personnel reporting a vaccination requirement or onsite vaccination availability compared with earlier influenza seasons might have contributed to the overall increase in vaccination coverage during the past 6 influenza seasons.
The influenza H1N1 pandemic of 1918 was one of the worst medical disasters in human history. Recent studies have demonstrated that the hemagglutinin (HA) protein of the 1918 virus and 2009 H1N1 pandemic virus, the latter now a component of the seasonal trivalent inactivated influenza vaccine (TIV),...
Galvao, Tais F.; Silva, Marcus T.; Zimmermann, Ivan R.; Lopes, Luiz Antonio B.; Bernardo, Eneida F.; Pereira, Mauricio G.
Objective. To assess the effects of the inactivated influenza virus vaccine on influenza outcomes in pregnant women and their infants. Methods. We performed a systematic review of the literature. We searched for randomized controlled trials and cohort studies in the MEDLINE, Embase, and other relevant databases (inception to September 2013). Two researchers selected studies and extracted the data independently. We used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach to assess the quality of the evidence. Results. We included eight studies out of 1,967 retrieved records. Influenza vaccination in pregnant women significantly reduced the incidence of influenza-like illness in mothers and their infants when compared with control groups (high-quality evidence) and reduced the incidence of laboratory-confirmed influenza in infants (moderate-quality evidence). No difference was found with regard to influenza-like illness with fever higher than 38°C (moderate-quality evidence) or upper respiratory infection (very-low-quality evidence) in mothers and infants. Conclusions. Maternal vaccination against influenza was shown to prevent influenza-like illness in women and infants; no differences were found for other outcomes. As the quality of evidence was not high overall, further research is needed to increase confidence and could possibly change these estimates. PMID:24971194
Olsen, Sonja J.; Mirza, Sara A.; Vonglokham, Phouvanh; Khanthamaly, Viengphone; Chitry, Bounlap; Pholsena, Vathsana; Chitranonh, Visith; Omer, Saad B.; Moen, Ann; Bresee, Joseph S.; Corwin, Andrew; Xeuatvongsa, Anonh
Background Some studies suggest that maternal influenza vaccination can improve birth outcomes. However, there are limited data from tropical settings, particularly Southeast Asia. We conducted an observational study in Laos to assess the effect of influenza vaccination in pregnant women on birth outcomes. Methods We consented and enrolled a cohort of pregnant woman who delivered babies at 3 hospitals during April 2014–February 2015. We collected demographic and clinical information on mother and child. Influenza vaccination status was ascertained by vaccine card. Primary outcomes were the proportion of live births born small for gestational age (SGA) or preterm and mean birth weight. Multivariate models controlled for differences between vaccinated and unvaccinated women and influenza virus circulation. Results We enrolled 5103 women (2172 [43%] were vaccinated). Among the 4854 who had a live birth, vaccinated women were statistically significantly less likely than unvaccinated women to have an infant born preterm during the period of high influenza virus circulation (risk ratio [RR] = 0.56, 95% confidence interval [CI], .45–.70), and the effect remained after adjusting for covariates (adjusted RR, 0.69; 95% CI, .55–.87). There was no effect of vaccine on SGA or mean birth weight. The population-prevented fraction was 18.0%. Conclusions In this observational study, we found indirect evidence of influenza vaccine safety during pregnancy, and women who received vaccine had a reduced risk of delivering a preterm infant during times of high influenza virus circulation. Vaccination may prevent 1 in 5 preterm births that occur during periods of high influenza circulation. PMID:27143672
Bond, K; Jones, K; Ompad, DC; Vlahov, D
In the United States, annual influenza vaccination rates are suboptimal and are well below the national health objectives. Project VIVA mobilized community members and organizations to implement an influenza vaccination program in Harlem by administering vaccines in “non-traditional” venues, such as community-based organizations, pharmacies, and faith-based organizations (FBOs). FBOs have been recognized as important venues for health promotion initiatives within medically underserved communities. However, data regarding the extent of resources and interest in health promotion programs among FBOs are sparse. We conducted a telephone survey among 115 FBOs in three New York City neighborhoods with histories of low influenza immunization rates to identify the congregation’s health concerns, interest in serving as a community-based venue for influenza vaccinations, and existing resources for health programming. Twenty-six percent of the FBOs had an established health ministry, while 45% expressed interest in developing one. Seven percent included nurses among their health activities and 16.5% had contact with the local health department. Most FBOs expressed interest in common health promotions programs; 60% expressed interest in providing on-site influenza vaccination programs within their organization. Health programs within FBOs can be a point of access that may improve the health of their congregants as well as the larger community. PMID:22623183
Stewart, Alexandra M; Cox, Marisa A
Nosocomial influenza outbreaks, attributed to the unvaccinated health care workforce, have contributed to patient complications or death, worker illness and absenteeism, and increased economic costs to the health care system. Since 1981, the Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention (CDC) has recommended that all HCP receive an annual influenza vaccination. Health care employers (HCE) have adopted various strategies to encourage health care personnel (HCP) to voluntarily receive influenza vaccination, including: sponsoring educational and promotional campaigns, increasing access to seasonal influenza vaccine, permitting the use of declination statements, and combining multiple approaches. However, these measures failed to significantly increase uptake among HCP. As a result, beginning in 2004, health care facilities and local health departments began to require certain HCP to receive influenza vaccination as a condition of employment and annually. Today, hundreds of facilities throughout the country have developed and implemented similar policies. Mandatory vaccination programs have been endorsed by professional and non-profit organizations, state health departments, and public health. These programs have been more effective at increasing coverage rates than any voluntary strategy, with some health systems reporting coverage rates up to 99.3%. Several states have enacted laws requiring HCEs to implement vaccination programs for the workforce. These laws present an example of how states will respond to threats to the public's health and constrain personal choice in order to protect vulnerable populations. This study analyzes laws in twenty states that address influenza vaccination requirements for HCP who practice in acute or long-term care facilities in the United States. The laws vary in the extent to which they incorporate the six elements of a mandatory HCP influenza vaccination program. Four of the
Cook, Ian F
A 76-year-old male presented with subacromial/subdeltoid bursitis following influenza vaccine administration into the left deltoid muscle. This shoulder injury related to vaccine administration (SIRVA) could have been prevented by the use of a safe, evidence based protocol for the intramuscular injection of the deltoid muscle.
Salk, Jonas; Salk, Darrell
Discusses control of poliomyelitis and influenza by live and killed virus vaccines. Considered are the etiological agents, pathogenic mechanisms and epidemiology of each disease. Reviews recent scientific studies of the diseases. Recommends use of killed virus vaccines in controlling both diseases. (CS)
Cook, Ian F
A 76-year-old male presented with subacromial/subdeltoid bursitis following influenza vaccine administration into the left deltoid muscle. This shoulder injury related to vaccine administration (SIRVA) could have been prevented by the use of a safe, evidence based protocol for the intramuscular injection of the deltoid muscle. PMID:24284281
Universal childhood influenza vaccination presents challenges and opportunities for health care and public health systems to vaccinate the children who fall under the new recommendation. Advisory Committee on Immunization Practices (ACIP) recommendations and guidelines are helpful, but they do not provide strategies on how to deliver immunization…
Kidd, Francine; Wones, Robert; Momper, Adam; Bechtle, Mavis; Lewis, Margaret
We believe we are the first union hospital to succeed in mandating the seasonal influenza vaccine for employees and physicians. We relate the process that we used to achieve this success. Our main purpose is to share our success with other colleagues in the health care industry who are facing similar opposition to mandatory vaccination.
Ahmed, S. Sohail; Steinman, Lawrence
ABSTRACT We previously reported an increased frequency of antibodies to hypocretin (HCRT) receptor 2 in sera obtained from narcoleptic patients who received the European AS03-adjuvanted vaccine Pandemrix (GlaxoSmithKline Biologicals, s.a.) for the global influenza A H1N1 pandemic in 2009 [A(H1N1)pdm09]. These antibodies cross-reacted with a particular fragment of influenza nucleoprotein (NP) – one of the proteins naturally contained in the virus used to make seasonal influenza vaccine and pandemic influenza vaccines. The purpose of this commentary is to provide additional insights and interpretations of the findings and share additional data not presented in the original paper to help the reader appreciate the key messages of that publication. First, a brief background to narcolepsy and vaccine-induced narcolepsy will be provided. Then, additional insights and clarification will be provided on the following topics: 1) the critical difference identified in the adjuvanted A(H1N1)pdm09 vaccines, 2) the contributing factor likely for the discordant association of narcolepsy between the AS03-adjuvanted pandemic vaccines Pandemrix and Arepanrix (GlaxoSmithKline Biologicals, s.a.), 3) the significance of detecting HCRT receptor 2 (HCRTr2) antibodies in some Finnish control subjects, 4) the approach used for the detection of HCRTr2 antibodies in vaccine-associated narcolepsy, and 5) the plausibility of the proposed mechanism involving HCRTr2 modulation in vaccine-associated narcolepsy. PMID:27031682
... taken in its entirety from the CDC Inactivated Influenza Vaccine Information Statement (VIS) www.cdc.gov/vaccines/hcp/vis/vis-statements/flu.html CDC review information for Inactivated Influenza VIS: ...
... entirety from the CDC Hib (Haemophilus Influenzae Type b) Vaccine Information Statement (VIS): www.cdc.gov/vaccines/ ... CDC review information for Hib (Haemophilus Influenzae Type b) VIS: Page last reviewed: April 2, 2015 Page ...
Improvements to the hemagglutination inhibition test for serological assessment of recombinant fowlpox-H5-avian-influenza vaccination in chickens and its use along with an agar gel immunodiffusion test for differentiating infected from noninfected vaccinated animals.
Swayne, David E; Avellaneda, Gloria; Mickle, Thomas R; Pritchard, Nikki; Cruz, Julio; Bublot, Michel
In general, avian influenza (AI) vaccines protect chickens from morbidity and mortality and reduce, but do not completely prevent, replication of wild AI viruses in the respiratory and intestinal tracts of vaccinated chickens. Therefore, surveillance programs based on serological testing must be developed to differentiate vaccinated flocks infected with wild strains of AI virus from noninfected vaccinated flocks in order to evaluate the success of vaccination in a control program and allow continuation of national and international commerce of poultry and poultry products. In this study, chickens were immunized with a commercial recombinant fowlpox virus vaccine containing an H5 hemagglutinin gene from A/turkey/Ireland/83 (H5N8) avian influenza (AI) virus (rFP-H5) and evaluated for correlation of immunological response by hemagglutination inhibition (HI) or agar gel immunodiffusion (AGID) tests and determination of protection following challenge with a high pathogenicity AI (HPAI) virus. In two different trials, chickens immunized with the rFP-H5 vaccine did not develop AGID antibodies because the vaccine lacks AI nucleoprotein and matrix genes, but 0%-100% had HI antibodies, depending on the AI virus strain used in the HI test, the HI antigen inactivation procedure, and whether the birds had been preimmunized against fowlpox virus. The most consistent and highest HI titers were observed when using A/turkey/Ireland/83 (H5N8) HPAI virus strain as the beta-propiolactone (BPL)-inactivated HI test antigen, which matched the hemagglutinin gene insert in the rFP-H5 vaccine. In addition, higher HI titers were observed if ether or a combination of ether and BPL-inactivated virus was used in place of the BPL-inactivated virus. The rFP-H5 vaccinated chickens survived HPAI challenge and antibodies were detected by both AGID and HI tests. In conclusion, we demonstrated that the rFP-H5 vaccine allowed easy serological differentiation of infected from noninfected birds in
Gross, P A; Weksler, M E; Quinnan, G V; Douglas, R G; Gaerlan, P F; Denning, C R
A total of 104 elderly patients were immunized with one or two doses of the commercial 1985-1986 inactivated influenza vaccine formulation. Two types of vaccines (split virus [SV] vaccine and whole virus [WV] vaccine) and one or two doses 1 month apart were given. No difference in local or systemic reactions was noted among the four groups. The reciprocal geometric mean hemagglutination inhibition antibody titers against influenza A/Philippines/82 (H3N2) after one or two doses were: 78 for SV vaccine (one dose), 65 for SV vaccine (two doses), 55 for WV vaccine (one dose), and 51 for WV vaccine (two doses). Similar nonsignificant differences were observed for the other two antigens contained in the vaccine. The percentage with a hemagglutination inhibition titer of greater than or equal to 1:40 also did not differ after one or two doses. We then compared the postvaccination hemagglutination inhibition titers in young and old patients from previous studies in which apparent differences had appeared. We retested all sera simultaneously on the same day with the same reagents. No significant differences were apparent among age groups. In summary, the humoral immune response to inactivated influenza vaccine in healthy ambulatory elderly patients who have been previously immunized may not differ significantly from that of children and young adults. A booster dose 1 month after the first dose does not enhance immune responses in the elderly.
Evans, Andrew M; Wood, Fiona C; Carter, Ben
Background Influenza is a significant cause of morbidity and excess mortality, yet vaccine coverage in the UK remains below target. Community pharmacies are increasingly being promoted as an alternative to vaccination by GPs. Aim To explore and verify the factors that influence the relative performance of pharmacies providing NHS influenza vaccinations. Design and setting A mixed methods study utilising qualitative, semi-structured interviews and quantitative analysis of predictors of vaccination numbers in community pharmacies in Wales. Method Interviews were conducted with 16 pharmacists who participated in the Welsh national pharmacy influenza service in 2013–2014. A purposive sampling strategy was used. Qualitative findings were analysed using framework analysis. Potential predictors of vaccination numbers were identified from interviews and a literature review, and included in a multivariable regression model. Results The contribution of community pharmacies towards vaccination in Wales is small. Findings suggest that community pharmacies reach younger at-risk individuals, in whom vaccine uptake is low, in greater proportion than influenza vaccination programmes as a whole. Extended opening hours and urban locations were positively associated with the number of vaccinations given, although pharmacists reported that workload, vaccine costs, unforeseen delays, lack of public awareness, and GPs’ views of the service limited their contribution. Pharmacists, aware of the potential for conflict with GPs, moderated their behaviour to mitigate such risk. Conclusion Before community pharmacies take greater responsibility for delivering healthcare services, obstacles including increasing pharmacist capacity, vaccine procurement, health service delays, managing GP–pharmacy relationships, and improving public awareness must be overcome. PMID:26965025
Wen, Yingxia; Han, Liqun; Palladino, Giuseppe; Ferrari, Annette; Xie, Yuhong; Carfi, Andrea; Dormitzer, Philip R; Settembre, Ethan C
Influenza vaccines are the primary intervention for reducing the substantial health burden from pandemic and seasonal influenza. Hemagglutinin (HA) is the most important influenza vaccine antigen. Subunit and split influenza vaccines are formulated, released for clinical use, and tested for stability based on an in vitro potency assay, single-radial immunodiffusion (SRID), which selectively detects HA that is immunologically active (capable of eliciting neutralizing or hemagglutination inhibiting antibodies in an immunized subject). The time consuming generation of strain-specific sheep antisera and calibrated antigen standards for SRID can delay vaccine release. The limitation in generating SRID reagents was evident during the early days of the 2009 pandemic, prompting efforts to develop more practical, alternative, quantitative assays for immunologically active HA. Here we demonstrate that, under native conditions, trypsin selectively digests HA produced from egg or mammalian cell in monovalent vaccines that is altered by stress conditions such as reduced pH, elevated temperature, or deamidation, leaving native, pre-fusion HA, intact. Subsequent reverse-phase high pressure liquid chromatography (RP-HPLC) can separate trypsin-resistant HA from the digested HA. Integration of the resulting RP-HPLC peak yields HA quantities that match well the values obtained by SRID. Therefore, trypsin digestion, to pre-select immunologically active HA, followed by quantification by RP-HPLC is a promising alternative in vitro potency assay for influenza vaccines.
Yang, Hye Jung; Cho, Sung-Il
The aim of this study was to examine seasonal and pandemic influenza vaccination coverage in adults from the 2008-2009 season to the 2011-2012 season, including pandemic and post-pandemic seasons in Korea. We collected data of self-reported vaccine use from the Korean Community Health Survey. We also collected information on socioeconomic status and health behaviors in subpopulations. We tested for linear trends among the data to investigate vaccine coverage before and after the pandemic; and multiple logistic regression analyses were performed to identify predictors of obtaining the influenza vaccination. The results revealed a steady increase in vaccination coverage in every subgroup during four consecutive seasons. The highest rate of vaccine coverage (43.6%) occurred two years after the pandemic. Factors associated with vaccine receipt were: older age; lower education level; lower income; and health behaviors such as regular walking and receiving a health check-up. Smoking and drinking alcohol were inversely associated with vaccination. Having a chronic health condition was also a strong predictor of vaccine receipt. Though vaccination coverage rates were high in high-risk groups; disparities in coverage rates were substantial; particularly in young adults. Interventions are needed to minimize the coverage gaps among subgroups and to improve overall vaccination rates.
Leiderman, Eduardo; Mogabgab, William J.
An experimental vaccine prepared from influenza virus strains propagated in bovine kidney cell cultures, purified by zonal centrifugation, and further treated with ether was studied in man for the incidence of clinical reactions and hemagglutination-inhibition antibody levels induced. The results were equivalent to those obtained in a simultaneous study made with a commercially licensed influenza vaccine derived from viruses propagated in the embryonated egg and also purified by zonal centrifugation, but not treated with ether. Comparison of the macromethod and the micromethod for determination of hemagglutination-inhibition antibody titers revealed that lower initial titers and lesser increments in antibody levels following vaccination were obtained by the microtechnique. PMID:4905036
Moreno-Pérez, D; Arístegui Fernández, J; Ruiz-Contreras, J; Alvarez García, F J; Merino Moína, M; González-Hachero, J; Corretger Rauet, J M; Hernández-Sampelayo Matos, T; Ortigosa del Castillo, L; Cilleruelo Ortega, M J; Barrio Corrales, F
The Advisory Committee on Vaccines of the Spanish Association of Paediatrics establishes annual recommendations on influenza vaccination in childhood before the onset of influenza season. Routine influenza vaccination is particularly beneficial when the strategy is aimed at children older than 6 months of age with high-risk conditions and their home contacts. The recommendation of influenza vaccination in health workers with children is also emphasized.
The 2010--11 influenza season was unusual because it followed the 2009 influenza A pandemic (H1N1) season and it was the first season the Advisory Committee on Immunization Practices (ACIP) recommended influenza vaccination of all persons aged ≥6 months. The season also was notable because a record number of seasonal influenza vaccine doses (approximately 163 million) were distributed in the United States. To provide preliminary state-specific influenza vaccination coverage estimates, CDC analyzed Behavioral Risk Factor Surveillance System (BRFSS) data for adults aged ≥18 years and National Immunization Survey (NIS) data for children aged 6 months-17 years collected September 2010 through March 2011. By February 28, the preliminary national vaccination coverage estimate was 49.0% for children aged 6 months-17 years; among 43 states and the District of Columbia (DC), coverage ranged from 30.2% for adults aged 18-49 years to 68.6% for adults aged ≥65 years. The record high seasonal vaccination coverage achieved during 2009-10 (41.3%) among persons aged ≥6 months in 43 states and DC was sustained during the 2010--11 season (42.8%). Coverage for Hispanic and non-Hispanic black children increased by 11-12 percentage points from 2009-10 levels. Opportunity exists to improve coverage in all age groups, particularly among adults. To accomplish that, health departments and other nonoffice-based vaccination providers can increase access to vaccination at work and school locations, pharmacies and stores, and other nonmedical sites. In addition, physicians and clinics should implement proven strategies for improving vaccination coverage (e.g., office-based protocols, including reminder/recall notification and standing orders).
Shahrabani, Shosh; Benzion, Uri
The study examined the factors affecting the decision to be vaccinated against influenza among employees in Israel. The research, conducted in 2007/2008, included 616 employees aged 18−65 at various workplaces in Israel, among them companies that offered their employees influenza vaccination. The research questionnaire included socio-demographic characteristics, and the Health Belief Model principles. The results show that the significant factors affecting vaccination compliance include a vaccination program at workplaces, vaccinations in the past, higher levels of vaccine’s perceived benefits, and lower levels of barriers to getting the vaccine. We conclude that vaccine compliance is larger at companies with workplace vaccination programs providing easier accessibility to vaccination. PMID:20617008
Bayas Rodríguez, José M; García-Basteiro, Alberto L; Mena Pinilla, Guillermo
Given the threat of an avian influenza A (H5N1) pandemic, vaccines that could be used in a new influenza pandemic began to be developed in 2004. The possible pandemic scenarios included highly serious situations with high incidence and mortality. Due to the need for the greatest possible number of vaccines to be available in a short period of time, studies with "model" vaccines were started, which allowed the immunogenicity and safety of the vaccines to be determined before identifying which virus would cause the pandemic. The use of adjuvants also formed part of these strategies. Subsequently, studies with the pandemic A (H1N1) strain were performed and additional studies continue to be performed. The vaccination strategies adopted have not been aimed at containing the infection but rather at ameliorating its effects. The choice of candidate groups for vaccination was not made hastily but after evaluating a large body of information on the epidemiology of the disease and the characteristics of the available vaccines. The population to be vaccinated is basically the same as that recommended to undergo seasonal influenza vaccination. In the ethical context of primum non nocere special emphasis has been placed on the vaccination of health personnel. All the available information supports the safety of the adjuvants and preservatives used in some of the authorized vaccines, as stated by the World Health Organization and many other prestigious organizations. So far 65 million doses have been administered throughout the world and the various adverse events detected by surveillance systems have been similar to those observed with other influenza vaccines and those that could be expected among millions of persons. Lessons must be drawn from the course of the present pandemic and the strategies used to deal with this situation as there will be other pandemics.
... Influenza Vaccination Week, 2010 8472 Proclamation 8472 Presidential Documents Proclamations Proclamation 8472 of January 8, 2010 Proc. 8472 National Influenza Vaccination Week, 2010By the President of the... complications, resulting in hospitalization or even death. We know that influenza vaccination is the best way...
Black, Steven; Nicolay, Uwe; Del Giudice, Giuseppe; Rappuoli, Rino
Influenza vaccination strategies have targeted elderly individuals because they are at high risk of disease complications and mortality. Statins are a class of drugs used to treat hypercholesterolemia and are frequently used in the elderly population to reduce the risk of cardiovascular disease. However, statins are also known to have immunomodulatory effects that could impact influenza vaccine response. In a post hoc analysis, we performed a cross-sectional observational study nested within a comparative immunogenicity clinical trial of adjuvanted versus unadjuvanted influenza vaccine in elderly persons to evaluate the influence of statin therapy on the immune response to vaccination. Overall, data on >5000 trial participants were available for analysis. Comparison of hemagglutination-inhibiting geometric mean titers to influenza A(H1N1), A(H3N2), and B strains revealed that titers were 38% (95% confidence interval [CI], 27%-50%), 67% (95% CI, 54%-80%), and 38% (95% CI, 28%-29%) lower, respectively, in subjects receiving chronic statin therapy, compared with those not receiving chronic statin therapy. This apparent immunosuppressive effect of statins on the vaccine immune response was most dramatic in individuals receiving synthetic statins. These effects were seen in both the adjuvanted and unadjuvanted vaccine groups in the clinical trial. These results, if confirmed, could have implications both for future clinical trials design, as well as for vaccine use recommendations for elderly individuals.
de PAULA, Stéfano Ivani; de PAULA, Gustavo Ivani; CUNEGUNDES, Kelly Simone Almeida; de MORAES-PINTO, Maria Isabel
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
Paula, Stéfano Ivani de; Paula, Gustavo Ivani de; Cunegundes, Kelly Simone Almeida; Moraes-Pinto, Maria Isabel de
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.
Zholobak, Nadezhda M; Mironenko, Alla P; Shcherbakov, Alexander B; Shydlovska, Olga A; Spivak, Mykola Ya; Radchenko, Larysa V; Marinin, Andrey I; Ivanova, Olga S; Baranchikov, Alexander E; Ivanov, Vladimir K
We have demonstrated the influence of cerium dioxide nanoparticles on the immunogenicity of the influenza vaccine on an example of liquid split inactivated Vaxigrip vaccine. Antibody titers were analyzed using the hemagglutination inhibition (HI) assay. Seroprotection, seroconversion, the geometric mean titers (GMTs) and the factor increase (FI) in the GMTs were calculated. The effect of nano-ceria surface stabilizer on the enhancement of immunogenicity was shown. The vaccine modified by citrate-stabilized nano-ceria, in contrast to a non-modified Vaxigrip vaccine, did not provide an adequate level of seroprotection, and seroconversion after vaccination was 66.7% on days 49-63 for virus strain А(H1N1) and 100% on day 49 for virus strain B/Yamagata. For the low immunogenic influenza B virus, the rise in antibody titers (GMT/IF) was 24.38/3.28 after the first injection and 50.40/6.79 on day 49. For the vaccine modified by non-stabilized nano-ceria, for all virus strains under study, on day 63, upon immunization notable levels of seroprotection, seroconversion and GMT/IF were registered (higher than for the non-modified Vaxigrip vaccine). The successful attempt to modify the influenza vaccine demonstrates the possible ways of increasing the specific activity of vaccines using nano-ceria.
Rocchi, G.; Ragona, G.; Piga, C.; Pelosio, A.; Volpi, A.; Vella, S.; Legniti, N.; de Felici, A.
Immunization procedures with live attenuated and inactivated vaccines were carried out on a group of young recruits at the beginning of an outbreak of infection due to an A/Victoria/3/75-related virus strain, which occurred in February 1977 in a military camp. A retrospective investigation on protection from clinical influenza was then performed in order to investigate whether immunization with live virus vaccines, administered at the beginning of an epidemic, could provide early protection from the disease. In the course of the two weeks following vaccination, laboratory-confirmed clinical influenza cases occurred in 4 subjects among the 110 volunteers of the control group which received placebo, and in 8, 7 and 4 subjects respectively of the 3 groups of about 125 individuals, each of which received one of the following vaccine preparations: (a), live attenuated A/Victoria/3/75 influenza virus oral vaccine, grown on chick embryo kidney culture; (b), live attenuated nasal vaccine, a recombinant of A/Puerto Rico/8/34 with A/Victoria/3/75 virus; and (c), inactivated A/Victoria/3/75 virus intramuscular vaccine. These data do not support the hypothesis that, during an epidemic of infection, early protection from clinical influenza can be achieved through immunization with live attenuated or inactivated influenza virus vaccines, in spite of the high immunizing capability of the vaccine preparations. PMID:512351
Kashirina, O S; Vasil'ev, Iu M
Comparative evaluation of live attenuated and inactivated influenza vaccines based on data from direct comparative studies is necessary for ensuring the most effective and safe vaccination against influenza. Analysis of direct comparative preclinical and clinical studies of inactivated and live cold-adapted (ca) influenza vaccines showed that published data are inconsistent and limited for some population groups. Live ca vaccines may be promising as an alternative or addition to inactivated vaccines especially for mass vaccination against influenza in children as well as in the elderly when combined with inactivated vaccines. Further studies of inactivated and live ca influenza vaccines in direct comparative studies that control the administration route and vaccine strain production as well as development and confirmation of objective criteria of live attenuated influenza vaccine effectiveness evaluation are necessary.
Shahar, Irit; Mendelson, Gad; Ben Natan, Merav
The factors affecting influenza vaccine uptake among nurses might vary between different medical facilities. The purpose of the present study was to explore factors that affect the intention of nurses at a long-term care facility to receive the influenza vaccine and whether the health belief model predicts this intention. In this cross-sectional quantitative correlational study, a convenience sample of 150 nurses employed at a large long-term care facility in central Israel completed a questionnaire based on the health belief model. Data collection took place between January and February of 2016. Forty-two percent of the respondents reported having been vaccinated against influenza in the current year. The health belief model explained 53% of the variance (p < .01), with perceived (personal) benefits of the vaccine being the most significant factor. The number of times of receiving the influenza vaccine in the past was strongly correlated with the intention to receive the vaccine (p < .01). To improve nurses' compliance with influenza vaccination at long-term care facilities, we find that it is necessary to emphasize the benefits of vaccination and, particularly, the personal benefits. Annual vaccination behavior should be promoted to make it become a routine.
Castilla, Jesús; Guevara, Marcela; Martínez-Baz, Iván; Ezpeleta, Carmen; Delfrade, Josu; Irisarri, Fátima; Moreno-Iribas, Conchi
Abstract Mortality is a major end-point in the evaluation of influenza vaccine effectiveness. However, this effect is not well known, since most previous studies failed to show good control of biases. We aimed to estimate the effectiveness of influenza vaccination in preventing all-cause mortality in community-dwelling seniors. Since 2009, a population-based cohort study using healthcare databases has been conducted in Navarra, Spain. In 2 late influenza seasons, 2011/2012 and 2012/2013, all-cause mortality in the period January to May was compared between seniors (65 years or over) who received the trivalent influenza vaccine and those who were unvaccinated, adjusting for demographics, major chronic conditions, dependence, previous hospitalization, and pneumococcal vaccination. The cohort included 103,156 seniors in the 2011/2012 season and 105,140 in the 2012/2013 season (58% vaccinated). Seniors vaccinated in the previous season who discontinued vaccination (6% of the total) had excess mortality and were excluded to prevent frailty bias. The final analysis included 80,730 person-years and 2778 deaths. Vaccinated seniors had 16% less all-cause mortality than those unvaccinated (adjusted rate ratio [RR] = 0.84; 95% confidence interval 0.76–0.93). This association disappeared in the post-influenza period (adjusted RR = 0.96; 95% confidence interval 0.85–1.09). A similar comparison did not find an association in January to May of the 2009/2010 pandemic season (adjusted RR = 0.98; 95% confidence interval 0.84–1.14), when no effect of the seasonal vaccine was expected. On average, 1 death was prevented for every 328 seniors vaccinated: 1 for every 649 in the 65 to 74 year age group and 1 for every 251 among those aged 75 and over. These results suggest a moderate preventive effect and a high potential impact of the seasonal influenza vaccine against all-cause mortality. This reinforces the recommendation of annual influenza vaccination in seniors
Hadler, James L
In order to consider the ethical issues around vaccine distribution during an influenza pandemic, it is critical to have an understanding of the role of influenza vaccine in a pandemic, the rate at which vaccine is likely to be come available, who will likely produce and "own" the vaccine, how vaccine distribution and administration might be accomplished, and which are the groups that might be deemed highest priority to be vaccinated against influenza. The United States and Connecticut have been considering the more challenging of these issues and have learned from Canada, which previously discussed and made decisions on the challenges related to vaccine distribution. Although there is still some critical advance thinking that needs to be done, planning for the response to an influenza pandemic is now at an advanced stage. The keys to preparedness at this stage are to be aware of the vaccine distribution options, to know the benefits and limitations of each option, and to be flexible but nimble in dealing with a real pandemic.
Milián, Ernest; Kamen, Amine A.
Annually, influenza virus infects millions of people worldwide. Vaccination programs against seasonal influenza infections require the production of hundreds of million doses within a very short period of time. The influenza vaccine is currently produced using a technology developed in the 1940s that relies on replicating the virus in embryonated hens' eggs. The monovalent viral preparation is inactivated and purified before being formulated in trivalent or tetravalent influenza vaccines. The production process has depended on a continuous supply of eggs. In the case of pandemic outbreaks, this mode of production might be problematic because of a possible drastic reduction in the egg supply and the low flexibility of the manufacturing process resulting in a lack of supply of the required vaccine doses in a timely fashion. Novel production systems using mammalian or insect cell cultures have emerged to overcome the limitations of the egg-based production system. These industrially well-established production systems have been primarily selected for a faster and more flexible response to pandemic threats. Here, we review the most important cell culture manufacturing processes that have been developed in recent years for mass production of influenza vaccines. PMID:25815321
Jang, Yo Han; Seong, Baik Lin
Since the discovery of antibodies specific to a highly conserved stalk region of the influenza virus hemagglutinin (HA), eliciting such antibodies has been considered the key to developing a universal influenza vaccine that confers broad-spectrum protection against various influenza subtypes. To achieve this goal, a prime/boost immunization strategy has been heralded to redirect host immune responses from the variable globular head domain to the conserved stalk domain of HA. While this approach has been successful in eliciting cross-reactive antibodies against the HA stalk domain, protective efficacy remains relatively poor due to the low immunogenicity of the domain, and the cross-reactivity was only within the same group, rather than among different groups. Additionally, concerns are raised on the possibility of vaccine-associated enhancement of viral infection and whether multiple boost immunization protocols would be considered practical from a clinical standpoint. Live attenuated vaccine hitherto remains unexplored, but is expected to serve as an alternative approach, considering its superior cross-reactivity. This review summarizes recent advancements in the HA stalk-based universal influenza vaccines, discusses the pros and cons of these approaches with respect to the potentially beneficial and harmful effects of neutralizing and non-neutralizing antibodies, and suggests future guidelines towards the design of a truly protective universal influenza vaccine.
Karch, Christopher P; Li, Jianping; Kulangara, Caroline; Paulillo, Sara M; Raman, Senthil K; Emadi, Sharareh; Tan, Anmin; Helal, Zeinab H; Fan, Qing; Khan, Mazhar I; Burkhard, Peter
Current influenza vaccines should be improved by the addition of universal influenza vaccine antigens in order to protect against multiple virus strains. We used our self-assembling protein nanoparticles (SAPNs) to display the two conserved influenza antigens M2e and Helix C in their native oligomerization states. To further improve the immunogenicity of the SAPNs, we designed and incorporated the TLR5 agonist flagellin into the SAPNs to generate self-adjuvanted SAPNs. We demonstrate that addition of flagellin does not affect the ability of SAPNs to self-assemble and that they are able to stimulate TLR5 in a dose-dependent manner. Chickens vaccinated with the self-adjuvanted SAPNs induce significantly higher levels of antibodies than those with unadjuvanted SAPNs and show higher cross-neutralizing activity compared to a commercial inactivated virus vaccine. Upon immunization with self-adjuvanted SAPNs, mice were completely protected against a lethal challenge. Thus, we have generated a self-adjuvanted SAPN with a great potential as a universal influenza vaccine.
Dormitzer, Philip R; Suphaphiphat, Pirada; Gibson, Daniel G; Wentworth, David E; Stockwell, Timothy B; Algire, Mikkel A; Alperovich, Nina; Barro, Mario; Brown, David M; Craig, Stewart; Dattilo, Brian M; Denisova, Evgeniya A; De Souza, Ivna; Eickmann, Markus; Dugan, Vivien G; Ferrari, Annette; Gomila, Raul C; Han, Liqun; Judge, Casey; Mane, Sarthak; Matrosovich, Mikhail; Merryman, Chuck; Palladino, Giuseppe; Palmer, Gene A; Spencer, Terika; Strecker, Thomas; Trusheim, Heidi; Uhlendorff, Jennifer; Wen, Yingxia; Yee, Anthony C; Zaveri, Jayshree; Zhou, Bin; Becker, Stephan; Donabedian, Armen; Mason, Peter W; Glass, John I; Rappuoli, Rino; Venter, J Craig
During the 2009 H1N1 influenza pandemic, vaccines for the virus became available in large quantities only after human infections peaked. To accelerate vaccine availability for future pandemics, we developed a synthetic approach that very rapidly generated vaccine viruses from sequence data. Beginning with hemagglutinin (HA) and neuraminidase (NA) gene sequences, we combined an enzymatic, cell-free gene assembly technique with enzymatic error correction to allow rapid, accurate gene synthesis. We then used these synthetic HA and NA genes to transfect Madin-Darby canine kidney (MDCK) cells that were qualified for vaccine manufacture with viral RNA expression constructs encoding HA and NA and plasmid DNAs encoding viral backbone genes. Viruses for use in vaccines were rescued from these MDCK cells. We performed this rescue with improved vaccine virus backbones, increasing the yield of the essential vaccine antigen, HA. Generation of synthetic vaccine seeds, together with more efficient vaccine release assays, would accelerate responses to influenza pandemics through a system of instantaneous electronic data exchange followed by real-time, geographically dispersed vaccine production.
Andrews, Ross M; Skull, Susan A; Byrnes, Graham B; Campbell, Donald A; Turner, Joy L; McIntyre, Peter B; Kelly, Heath A
This study was undertaken to assess the uptake of influenza and pneumococcal vaccination based on provider records of the hospitalised elderly, a group at high risk of influenza and pneumococcal disease. The study used a random sample of 3,204 admissions at two Victorian teaching hospitals for patients, aged 65 years or more who were discharged between 1 April 2000 and 31 March 2002. Information on whether the patient had received an influenza vaccination within the year prior to admission or pneumococcal vaccination within the previous five years was ascertained from the patient's nominated medical practitioner/vaccine provider. Vaccination records were obtained from providers for 82 per cent (2,804/2,934) of eligible subjects. Influenza vaccine coverage was 70.9 per cent (95% CI 68.9-72.9), pneumococcal coverage was 52.6 per cent (95% CI 50.4-54.8) and 46.6 per cent (95% CI 44.4-48.8) had received both vaccines. Coverage for each vaccine increased seven per cent over the two study years. For pneumococcal vaccination, there was a marked increase in 1998 coinciding with the introduction of Victoria's publicly funded program. Influenza and pneumococcal vaccine coverage in eligible hospitalised adults was similar to, but did not exceed, estimates in the general elderly population. Pneumococcal vaccination coverage reflected the availability of vaccine through Victoria's publicly funded program. A nationally funded pneumococcal vaccination program for the elderly, as announced recently, should improve coverage. However, these data highlight the need for greater awareness of pneumococcal vaccine among practitioners and for systematic recording of vaccination status, as many of these subjects will soon become eligible for revaccination.
Winokur, Patricia L; Patel, Shital M; Brady, Rebecca; Chen, Wilbur H; El-Kamary, Samer S; Edwards, Kathryn; Creech, C Buddy; Frey, Sharon; Keitel, Wendy A; Belshe, Robert; Walter, Emmanuel; Bellamy, Abbie; Hill, Heather
Influenza A(H5N1) vaccination strategies that improve the speed of the immunological response and cross-clade protection are desired. We compared the immunogenicity of a single 15-μg or 90-μg dose of A/H5N1/Indonesia/05/05 (clade 2) vaccine in adults who were previously primed with A/H5N1/Vietnam/1203/2004 (clade 1) vaccine. High-dose vaccine resulted in significantly higher titers to both clade 1 and 2 antigens. Clade 2 titers were unaffected by the previous dose of clade 1 vaccine. Low-dose priming with a mismatched pandemic influenza A(H5N1) vaccine would improve the rapidity, magnitude, and cross-reactivity of the immunological response following a single high-dose, unadjuvanted, pandemic vaccine.
Brown, Derek S; Arnold, Sarah E; Asay, Garrett; Lorick, Suchita A; Cho, Bo-Hyun; Basurto-Davila, Ricardo; Messonnier, Mark L
The use of alternative venues beyond physician offices may help to increase rates of population influenza vaccination. Schools provide a logical setting for reaching children, but most school-located vaccination (SLV) efforts to date have been limited to local areas. The potential reach and acceptability of SLV at the national level is unknown in the United States. To address this gap, we conducted a nationally representative online survey of 1088 parents of school-aged children. We estimate rates of, and factors associated with, future hypothetical parental consent for children to participate in SLV for influenza. Based on logistic regression analysis, we estimate that 51% of parents would be willing to consent to SLV for influenza. Among those who would consent, SLV was reported as more convenient than the regular location (42.1% vs. 19.9%, P<0.001). However the regular location was preferred over SLV for the child's well-being in case of side effects (46.4% vs. 20.9%, P<0.001) and proper administration of the vaccine (31.0% vs. 21.0%, P<0.001). Parents with college degrees and whose child received the 2009-2010 seasonal or 2009 H1N1 influenza vaccination were more likely to consent, as were parents of uninsured children. Several measures of concern about vaccine safety were negatively associated with consent for SLV. Of those not against SLV, schools were preferred as more convenient to the regular location by college graduates, those whose child received the 2009-2010 seasonal or 2009 H1N1 influenza vaccination, and those with greater travel and clinic time. With an estimated one-half of U.S. parents willing to consent to SLV, this study shows the potential to use schools for large-scale influenza vaccination programs in the U.S.
Gendon, Iu Z
Published data related with comparison studies of safety, efficiency and some other properties of cold-adapted live influenza vaccine (LIV) and of inactivated influenza vaccine (IIV) are analyzed. LIV and IIV do not differ by systemic reactions after administration; however, it is not ruled out that there can be unfavorable reactions in vaccination of persons with allergy to the chicken-embryo proteins as well as in cases of persistence/reversion of cold-adapted strain observed in vaccination of persons with primary impairments of the immune system. There are no convincing data, up to now, on that LIV is superior to IIV in coping with influenza pandemics. The efficiency of LIV and IIV for children aged 3 years and more and for healthy adults is virtually identical. Additional controllable field comparative studies of LIV and IIV efficiency in immunization of elderly persons are needed. Limited data on LIV efficiency for children aged 2 months and more were obtained. The need in a 2-stage vaccination of all age group with the aim of ensuring responses to all 3 LIV components is, certainly, a LIV disadvantage. In case of IIV, the 2-stage vaccination is needed only for persons who were not ill with influenza. The intranasal LIV administration has, from the practical and psychological standpoints, an advantage before the IIV administration by syringe. The ability of LIV to protect from the drift influenza-virus variations could be its advantage before IIV; still, more research is needed to verify it. Transplantable cell lines meeting the WHO requirements could be an optimal substrate for the production of LIV and IIV. Children are the optimal age group for influenza prevention by cold-adapted LIV, whereas, IIV fits better for vaccination of adults and elderly persons.
Atkins, Katherine; van Hoek, Albert Jan; Watson, Conall; Baguelin, Marc; Choga, Lethiwe; Patel, Anika; Raj, Thara; Jit, Mark; Griffiths, Ulla
Objective To evaluate the effectiveness and cost of the pan-London pharmacy initiative, a programme that allows administration of seasonal influenza vaccination to eligible patients at pharmacies. Design We analysed 2013–2015 data on vaccination uptake in pharmacies via the Sonar reporting system, and the total vaccination uptake via 2011–2015 ImmForm general practitioner (GP) reporting system data. We conducted an online survey of London pharmacists who participate in the programme to assess time use data, vaccine choice, investment costs and opinions about the programme. We conducted an online survey of London GPs to assess vaccine choice of vaccine and opinions about the pharmacy vaccine delivery programme. Setting All London boroughs. Participants London-based GPs, and pharmacies that currently offer seasonal flu vaccination. Interventions Not applicable. Main outcome measures Comparison of annual vaccine uptake in London across risk groups from years before pharmacy vaccination introduction to after pharmacy vaccination introduction. Completeness of vaccine uptake reporting data. Cost to the National Health Service (NHS) of flu vaccine delivery at pharmacies with that at GPs. Cost to pharmacists of flu delivery. Opinions of pharmacists and GPs regarding the flu vaccine pharmacy initiative. Results No significant change in the uptake of seasonal vaccination in any of the risk groups as a result of the pharmacy initiative. While on average a pharmacy-administered flu vaccine dose costs the NHS up to £2.35 less than a dose administered at a GP, a comparison of the 2 recording systems suggests there is substantial loss of data. Conclusions Flu vaccine delivery through pharmacies shows potential for improving convenience for vaccine recipients. However, there is no evidence that vaccination uptake increases and the use of 2 separate recording systems leads to time-consuming data entry and missing vaccine record data. PMID:26883237
Lee, Vernon J.; Tok, Mei Yin; Chow, Vincent T.; Phua, Kai Hong; Ooi, Eng Eong; Tambyah, Paul A.; Chen, Mark I.
Background All influenza pandemic plans advocate pandemic vaccination. However, few studies have evaluated the cost-effectiveness of different vaccination strategies. This paper compares the economic outcomes of vaccination compared with treatment with antiviral agents alone, in Singapore. Methodology We analyzed the economic outcomes of pandemic vaccination (immediate vaccination and vaccine stockpiling) compared with treatment-only in Singapore using a decision-based model to perform cost-benefit and cost-effectiveness analyses. We also explored the annual insurance premium (willingness to pay) depending on the perceived risk of the next pandemic occurring. Principal Findings The treatment-only strategy resulted in 690 deaths, 13,950 hospitalization days, and economic cost of USD$497 million. For immediate vaccination, at vaccine effectiveness of >55%, vaccination was cost-beneficial over treatment-only. Vaccine stockpiling is not cost-effective in most scenarios even with 100% vaccine effectiveness. The annual insurance premium was highest with immediate vaccination, and was lower with increased duration to the next pandemic. The premium was also higher with higher vaccine effectiveness, attack rates, and case-fatality rates. Stockpiling with case-fatality rates of 0.4–0.6% would be cost-beneficial if vaccine effectiveness was >80%; while at case-fatality of >5% stockpiling would be cost-beneficial even if vaccine effectiveness was 20%. High-risk sub-groups warrant higher premiums than low-risk sub-groups. Conclusions The actual pandemic vaccine effectiveness and lead time is unknown. Vaccine strategy should be based on perception of severity. Immediate vaccination is most cost-effective, but requires vaccines to be available when required. Vaccine stockpiling as insurance against worst-case scenarios is also cost-effective. Research and development is therefore critical to develop and stockpile cheap, readily available effective vaccines. PMID:19771173
Background Influenza vaccination is the most efficient and cost-effective method to prevent influenza. To increase vaccination coverage, health authorities use various intervention programs (IPs), such as cost subsidies or placing vaccination centers in malls to make vaccination more accessible. Nevertheless, vaccination coverage has been sub-optimal in most developed countries, including in Israel. Methods To determine possible drivers of individual vaccination uptake and to examine the effectiveness of different IPs in increasing vaccination, we analyzed a telephone survey of a representative sample of the Israeli population conducted in March 2011 (n = 470), and paper questionnaires at the work place and at homes during April-July 2011 to several sub-populations : soldiers (n = 81), medical staff (n = 107), ultra-orthodox Jews (n = 72), Israeli Arabs (n = 87) and students (n = 85). Results The population can be stratified into three sub-groups: Acceptors, who receive vaccination regardless of IPs (22%), Conditional Acceptors, who are only vaccinated because of IP implementation (44%) and Non-Acceptors, who are not vaccinated despite IP implementation (34%). Our analysis shows that the risk perception towards influenza relative to vaccination is higher in the Acceptors than in the Conditional Acceptors, with the Non-Acceptors showing the lowest risk perception (P < 0.01). For Conditional Acceptors, physician recommendation is the most effective IP, regardless of the sub-population tested (P = 0.04). Students and low-income participants were more prone than any others to be persuaded to receive vaccination following IPs. In addition, financial incentives were more effective for ultra-religious orthodox Jews and students; vaccinations in more accessible areas were more effective for the ultra-religious orthodox, soldiers, and medical personnel; and TV and radio advertisements were more effective for people above 50 relative to other
Flannery, Brendan; Chung, Jessie R; Thaker, Swathi N; Monto, Arnold S; Martin, Emily T; Belongia, Edward A; McLean, Huong Q; Gaglani, Manjusha; Murthy, Kempapura; Zimmerman, Richard K; Nowalk, Mary Patricia; Jackson, Michael L; Jackson, Lisa A; Foust, Angie; Sessions, Wendy; Berman, LaShondra; Spencer, Sarah; Fry, Alicia M
In the United States, annual vaccination against seasonal influenza is recommended for all persons aged ≥6 months (1). Each influenza season since 2004-05, CDC has estimated the effectiveness of seasonal influenza vaccine to prevent influenza-associated, medically attended, acute respiratory illness (ARI). This report uses data, as of February 4, 2017, from 3,144 children and adults enrolled in the U.S. Influenza Vaccine Effectiveness Network (U.S. Flu VE Network) during November 28, 2016-February 4, 2017, to estimate an interim adjusted effectiveness of seasonal influenza vaccine for preventing laboratory-confirmed influenza virus infection associated with medically attended ARI. During this period, overall vaccine effectiveness (VE) (adjusted for study site, age group, sex, race/ethnicity, self-rated general health, and days from illness onset to enrollment) against influenza A and influenza B virus infection associated with medically attended ARI was 48% (95% confidence interval [CI] = 37%-57%). Most influenza infections were caused by A (H3N2) viruses. VE was estimated to be 43% (CI = 29%-54%) against illness caused by influenza A (H3N2) virus and 73% (CI = 54%-84%) against influenza B virus. These interim VE estimates indicate that influenza vaccination reduced the risk for outpatient medical visits by almost half. Because influenza activity remains elevated (2), CDC and the Advisory Committee on Immunization Practices recommend that annual influenza vaccination efforts continue as long as influenza viruses are circulating (1). Vaccination with 2016-17 influenza vaccines will reduce the number of infections with most currently circulating influenza viruses. Persons aged ≥6 months who have not yet been vaccinated this season should be vaccinated as soon as possible.
Huang, Kuan-Ying A.; Chang, Shih-Cheng; Huang, Yhu-Chering; Chiu, Cheng-Hsun; Lin, Tzou-Yien
Inactivated influenza vaccination induces a hemagglutinin-specific antibody response to the strain used for immunization. Annual vaccination is strongly recommended for health care personnel. However, it is debatable if repeated vaccination would affect the antibody response to inactivated influenza vaccine through the time. We enrolled health care personnel who had repeated and first trivalent inactivated influenza vaccination in 2005–2008. Serological antibody responses were measured by hemagglutination-inhibition (HI) test. Subjects with repeated vaccination had higher pre-vaccination and lower post-vaccination HI titer than those with first vaccination, although serological responses between groups might vary with different antigen types and while the drifted strain was introduced in the vaccine. Higher fold rise in the HI titer was observed in the group with first than repeated vaccination and the fold increase in the HI titer was inversely correlated with pre-vaccination titer in 2007 and 2008. Nevertheless, no significant difference in the day 28 seroprotection rate was observed between groups with repeated and first vaccination in most circumstances. Further studies are needed to understand the long-term effect of repeated vaccination on the antibody response both at the serological and repertoire levels among health care personnel. PMID:28098157
Mossad, Sherif B
FluMist--a cold-adapted, live-attenuated, trivalent, intranasal influenza virus vaccine approved by the US Food and Drug Administration on June 17, 2003--has been shown to be safe and effective, but its role in the general prevention of influenza is yet to be defined. Intranasal administration is expected to be more acceptable than parenteral, particularly in children, but the potential for the shedding of live virus may pose a risk to anyone with a compromised immune system.
Dijkstra, Frederika; van Doorn, Eva; Bijlsma, Maarten J.; Donker, Gé A.; de Lange, Marit M. A.; Cadenau, Laura M.; Hak, Eelko; Meijer, Adam
Influenza vaccine effectiveness (IVE) varies over different influenza seasons and virus (sub)types/lineages. To assess the association between IVE and circulating influenza virus (sub)types/lineages, we estimated the overall and (sub)type specific IVE in the Netherlands. We conducted a test-negative case control study among subjects with influenza-like illness or acute respiratory tract infection consulting the Sentinel Practices over 11 influenza seasons (2003/2004 through 2013/2014) in the Netherlands. The adjusted IVE was estimated using generalized linear mixed modelling and multiple logistic regression. In seven seasons vaccine strains did not match the circulating viruses. Overall adjusted IVE was 40% (95% CI 18 to 56%) and 20% (95% CI -5 to 38%) when vaccine (partially)matched and mismatched the circulating viruses, respectively. When A(H3N2) was the predominant virus, IVE was 38% (95% CI 14 to 55%). IVE against infection with former seasonal A(H1N1) virus was 83% (95% CI 52 to 94%), and with B virus 67% (95% CI 55 to 76%). In conclusion IVE estimates were particularly low when vaccine mismatched the circulating viruses and A(H3N2) was the predominant influenza virus subtype. Tremendous effort is required to improve vaccine production procedure and to explore the factors that influence the IVE against A(H3N2) virus. PMID:28068386
Ahluwalia, Indu B; Singleton, James A; Jamieson, Denise J; Rasmussen, Sonja A; Harrison, Leslie
Since 2004, the American College of Obstetricians and Gynecologists (ACOG) and the Advisory Committee on Immunization Practices (ACIP) have recommended that pregnant women receive the seasonal influenza vaccine, regardless of pregnancy trimester, because of their increased risk for severe complications from influenza. However, the uptake of the influenza vaccine by pregnant women has been low. During the 2009-2010 influenza season, pregnant women were identified as a priority population to receive the influenza A (H1N1) 2009 (2009 H1N1) monovalent vaccine in addition to the seasonal influenza vaccine. In this issue, we highlight information from the 10 states that collected data using the survey administered by the Pregnancy Risk Assessment and Monitoring System (PRAMS) about seasonal vaccine coverage among women with recent live births and reasons for those who chose not to get vaccinated. The combined estimates from PRAMS of influenza vaccination coverage for the 2009-2010 season, which included data from October 2009 to March 2010, from 10 states were 50.7% for seasonal and 46.6% for 2009 H1N1 vaccine among women with recent live births. Among women who did not get vaccinated, reasons varied from worries about the safety of the vaccines for self and baby to not normally getting the vaccination. Further evaluation is needed on ways to increase influenza vaccination among pregnant women, effectively communicate the risk of influenza illness during pregnancy, and address women's concerns about influenza vaccination safety during pregnancy.
Murugappan, Senthil; Frijlink, Henderik W; Petrovsky, Nikolai; Hinrichs, Wouter L J
Vaccination is the primary intervention to contain influenza virus spread during seasonal and pandemic outbreaks. Pulmonary vaccination is gaining increasing attention for its ability to induce both local mucosal and systemic immune responses without the need for invasive injections. However, pulmonary administration of whole inactivated influenza virus (WIV) vaccine induces a Th2 dominant systemic immune response while a more balanced Th1/Th2 vaccine response may be preferred and only induces modest nasal immunity. This study evaluated immunity elicited by pulmonary versus intramuscular (i.m.) delivery of WIV, and tested whether the immune response could be improved by co-administration of delta (δ)-inulin, a novel carbohydrate-based particulate adjuvant. After pulmonary administration both unadjuvanted and δ-inulin adjuvanted WIV induced a potent systemic immune response, inducing higher serum anti-influenza IgG titers and nasal IgA titers than i.m. administration. Moreover, the addition of δ-inulin induced a more balanced Th1/Th2 response and induced higher nasal IgA titers versus pulmonary WIV alone. Pulmonary WIV alone or with δ-inulin induced hemagglutination inhibition (HI) titers>40, titers which are considered protective against influenza virus. In conclusion, in this study we have shown that δ-inulin adjuvanted WIV induces a better immune response after pulmonary administration than vaccine alone.
Spackman, Erica; Pantin-Jackwood, Mary J
Although little has changed in vaccine technology for avian influenza virus (AIV) in the past 20 years, the approach to vaccination of poultry (chickens, turkeys and ducks) for avian influenza has evolved as highly pathogenic AIV has become endemic in several regions of the world. Vaccination for low pathogenicity AIV is also becoming routine in regions where there is a high level of field challenge. In contrast, some countries will not use vaccination at all and some will only use it on an emergency basis during eradication efforts (i.e. stamping-out). There are pros and cons to each approach and, since every outbreak situation is different, no one method will work equally well in all situations. Numerous practical aspects must be considered when developing an AIV control program with vaccination as a component, such as: (1) the goals of vaccination must be defined; (2) the population to be vaccinated must be clearly identified; (3) there must be a plan to obtain and administer good quality vaccine in a timely manner and to achieve adequate coverage with the available resources; (4) risk factors for vaccine failure should be mitigated as much as possible; and, most importantly, (5) biosecurity must be maintained as much as possible, if not enhanced, during the vaccination period.
The influenza pandemic of 2009 demonstrated the inability of the established global capacity for egg-based vaccine production technology to provide sufficient vaccine for the population in a timely fashion. Several alternative technologies for developing influenza vaccines have been proposed, among which non-replicating virus-like particles (VLPs) represent an attractive option because of their safety and immunogenic characteristics. VLP vaccines against pandemic influenza have been developed in tobacco plant cells and in Sf9 insect cells infected with baculovirus that expresses protein genes from pandemic influenza strains. These technologies allow rapid and large-scale production of vaccines (3-12 weeks). The 2009 influenza outbreak provided an opportunity for clinical testing of a pandemic influenza VLP vaccine in the midst of the outbreak at its epicenter in Mexico. An influenza A(H1N1)2009 VLP pandemic vaccine (produced in insect cells) was tested in a phase II clinical trial involving 4,563 healthy adults. Results showed that the vaccine is safe and immunogenic despite high preexisting anti-A(H1N1)2009 antibody titers present in the population. The safety and immunogenicity profile presented by this pandemic VLP vaccine during the outbreak in Mexico suggests that VLP technology is a suitable alternative to current influenza vaccine technologies for producing pandemic and seasonal vaccines.
Scheminske, Megan; Henninger, Michelle; Irving, Stephanie A.; Thompson, Mark; Williams, Jenny; Shifflett, Pat; Ball, Sarah W.; Avalos, Lyndsay Ammon; Naleway, Allison L.
Objectives: Although pregnant women are a high-priority group for seasonal influenza vaccination, vaccination rates in this population remain below target levels. Previous studies have identified sociodemographic predictors of vaccine choice, but relationships between preconception heath behaviors and seasonal influenza vaccination are poorly…
de Castro, Breno Augusto Campos; Pereira, Juliana Milagres Macedo; Meyer, Renata Leal Bregunci; Trindade, Fernanda Marques; Pedrosa, Moises Salgado; Piancastelli, André Costa Cruz
The etiology of pityriasis lichenoides is unknown. One of the accepted theories admits that PL is an inflammatory response to extrinsic antigens such as infectious agents, drugs and vaccines. In recent medical literature, only the MMR vaccine (Measles, Mumps and Rubella) was associated with the occurrence of this disease. We present a case of a male, 12 year old healthy patient who, five days after Infl uenza vaccination, developed erythematous papules on the trunk, abdomen and limbs, some with adherent crusts and associated systemic symptoms. This case report is notable for describing the first case of pityriasis lichenoides et varioliformis acuta associated with the vaccine against Influenza. PMID:26312710
Curran, T; McCaughey, C; Ellis, J; Mitchell, S J; Feeney, S A; Watt, A P; Mitchell, F; Fairley, D; Crawford, L; McKenna, J; Coyle, P V
False-positive PCR results usually occur as a consequence of specimen-to-specimen or amplicon-to-specimen contamination within the laboratory. Evidence of contamination at time of specimen collection linked to influenza vaccine administration in the same location as influenza sampling is described. Clinical, circumstantial and laboratory evidence was gathered for each of five cases of influenza-like illness (ILI) with unusual patterns of PCR reactivity for seasonal H1N1, H3N2, H1N1 (2009) and influenza B viruses. Two 2010 trivalent influenza vaccines and environmental swabs of a hospital influenza vaccination room were also tested for influenza RNA. Sequencing of influenza A matrix (M) gene amplicons from the five cases and vaccines was undertaken. Four 2009 general practitioner (GP) specimens were seasonal H1N1, H3N2 and influenza B PCR positive. One 2010 GP specimen was H1N1 (2009), H3N2 and influenza B positive. PCR of 2010 trivalent vaccines showed high loads of detectable influenza A and B RNA. Sequencing of the five specimens and vaccines showed greatest homology with the M gene sequence of Influenza A/Puerto Rico/8/1934 H1N1 virus (used in generation of influenza vaccine strains). Environmental swabs had detectable influenza A and B RNA. RNA detection studies demonstrated vaccine RNA still detectable for at least 66 days. Administration of influenza vaccines and clinical sampling in the same room resulted in the contamination with vaccine strains of surveillance swabs collected from patients with ILI. Vaccine contamination should therefore be considered, particularly where multiple influenza virus RNA PCR positive signals (e.g. H1N1, H3N2 and influenza B) are detected in the same specimen.
Lambach, Philipp; Alvarez, Alba Maria Ropero; Hirve, Siddhivinayak; Ortiz, Justin R; Hombach, Joachim; Verweij, Marcel; Hendriks, Jan; Palkonyay, Laszlo; Pfleiderer, Michael
There is potential for influenza vaccine programmes to make a substantial impact on severe disease in low-resource settings, however questions around vaccine composition and programmatic issues will require special attention. Some countries may benefit from immunization programmes that provide year-round supply of vaccine; however the best way to ensure adequate vaccine supply has yet to be determined. In this report, we discuss vaccine composition, availability, and programmatic issues that must be considered when developing year-round influenza immunization programmes. We then explore how these considerations have influenced immunization practices in the Latin American region as a case study. We identify three different approaches to achieve year-round supply: (1) alternating between Northern Hemisphere and Southern Hemisphere formulations, (2) extending the expiration date to permit extended use of a single hemisphere formulation, and (3) local vaccine manufacture with production timelines that align with local epidemiology. Each approach has its challenges and opportunities. The growing data suggesting high influenza disease burden in low resource countries underscores the compelling public health need to determine the best strategies for vaccine delivery.
Song, Langzhou; Liu, Ge; Umlauf, Scott; Liu, Xiangyu; Li, Hong; Tian, Haijun; Reiserova, Lucia; Hou, Fuxiang; Bell, Rodney; Tussey, Lynda
Previously, we demonstrated that for H1N1 and H5N1 influenza strains, the globular head of the hemagglutinin (HA) antigen fused to flagellin of Salmonella typhimurium fljB (STF2) is highly immunogenic in preclinical models and man (Song et al. (2008) ; Song et al. (2009) ; Taylor et al. (2012) ). Further we showed that the vaccine format, or point of attachment of the vaccine antigen to flagellin, can dramatically affect the immunogenicity and safety profile of the vaccine. However, Influenza B vaccines based on these formats are poor triggers of TLR5 and consequently are poorly immunogenic. Through rational design, here we show that we have identified a fusion position within domain 3 of flagellin that improves TLR5 signaling and consequently, immunogenicity of multiple influenza B vaccines. Our results demonstrate that, similar to influenza A strains, the protective subunit of the influenza B HA can be fused to flagellin and produced in a standard prokaryotic expression system thereby allowing for cost and time efficient production of multivalent seasonal influenza vaccines.
GAMOH, Koichiro; NAKAMURA, Shigeyuki
Japan established a vaccine selection system, in which a committee evaluates veterinary influenza vaccines to determine if the vaccine should be updated. In 2013, it was concluded that the present equine influenza vaccine strains did not have to be updated, but clade 2 (Fc2) viruses of the Florida sublineage should be included. We collected three Fc2 viruses as candidates and conducted comparative tests. Results indicated that A/equine/Carlow/2011 (H3N8) is not suitable, because of its unstable antigenic characteristics. A comparison between A/equine/Richmond/1/2007 (H3N8) (Richmond/07) and A/equine/Yokohama/aq13/2010 (H3N8) (Yokohama/10) in eggs showed that they shared equal growth properties. Immunogenicity test in mice showed that Yokohama/10 induced higher HI antibody titers than Richmond/07. Therefore, we concluded that Yokohama/10 was the most suitable strain. PMID:28163276
Lambert, Laura; Kinnear, Ekaterina; McDonald, Jacqueline U.; Grodeland, Gunnveig; Bogen, Bjarne; Stubsrud, Elisabeth; Lindeberg, Mona M.; Fredriksen, Agnete Brunsvik; Tregoning, John S.
Current influenza vaccines are effective but imperfect, failing to cover against emerging strains of virus and requiring seasonal administration to protect against new strains. A key step to improving influenza vaccines is to improve our understanding of vaccine-induced protection. While it is clear that antibodies play a protective role, vaccine-induced CD8+ T cells can improve protection. To further explore the role of CD8+ T cells, we used a DNA vaccine that encodes antigen dimerized to an immune cell targeting module. Immunizing CB6F1 mice with the DNA vaccine in a heterologous prime-boost regime with the seasonal protein vaccine improved the resolution of influenza disease compared with protein alone. This improved disease resolution was dependent on CD8+ T cells. However, DNA vaccine regimes that induced CD8+ T cells alone were not protective and did not boost the protection provided by protein. The MHC-targeting module used was an anti-I-Ed single chain antibody specific to the BALB/c strain of mice. To test the role of MHC targeting, we compared the response between BALB/c, C57BL/6 mice, and an F1 cross of the two strains (CB6F1). BALB/c mice were protected, C57BL/6 were not, and the F1 had an intermediate phenotype; showing that the targeting of antigen is important in the response. Based on these findings, and in agreement with other studies using different vaccines, we conclude that, in addition to antibody, inducing a protective CD8 response is important in future influenza vaccines. PMID:27602032
Poland, Gregory A; Fleming, Douglas M; Treanor, John J; Maraskovsky, Eugene; Luke, Thomas C; Ball, Emma M A; Poland, Caroline M
Both seasonal and pandemic influenza cause considerable morbidity and mortality globally. In addition, the ongoing threat of new, unpredictable influenza pandemics from emerging variant strains cannot be underestimated. Recently bioCSL (previously known as CSL Biotherapies) sponsored a symposium 'New Wisdom to Defy an Old Enemy' at the 4th Influenza Vaccines for the World Congress in Valencia, Spain. This symposium brought together a renowned faculty of experts to discuss lessons from past experience, novel influenza vaccine developments, and new methods to increase vaccine acceptance and coverage. Specific topics reviewed and discussed included new vaccine development efforts focused on improving efficacy via alternative administration routes, dose modifications, improved adjuvants, and the use of master donor viruses. Improved safety was also discussed, particularly the new finding of an excess of febrile reactions isolated to children who received the 2010 Southern Hemisphere (SH) trivalent inactivated influenza vaccine (TIV). Significant work has been done to both identify the cause and minimize the risk of febrile reactions in children. Other novel prophylactic and therapeutic advances were discussed including immunotherapy. Standard IVIg and hIVIg have been used in ferret studies and human case reports with promising results. New adjuvants, such as ISCOMATRIX™ adjuvant, were noted to provide single-dose, prolonged protection with seasonal vaccine after lethal H5N1 virus challenge in a ferret model of human influenza disease. The data suggest that adjuvanted seasonal influenza vaccines may provide broader protection than unadjuvanted vaccines. The use of an antigen-formulated vaccine to induce broad protection between pandemics that could bridge the gap between pandemic declaration and the production of a homologous vaccine was also discussed. Finally, despite the availability of effective vaccines, most current efforts to increase influenza vaccine coverage
Miyaki, Cosue; Meros, Mauricio; Precioso, Alexander R; Raw, Isaias
Technology transfer is a promising approach to increase vaccine production at an affordable price in developing countries. In the case of influenza, it is imperative that developing countries acquire the technology to produce pandemic vaccines through the transfer of know-how, as this will be the only way for the majority of these countries to face the huge demand for vaccine created by influenza pandemics. Access to domestically produced influenza vaccine in such health crises is thus an important national defence strategy. However, technology transfer is not a simple undertaking. It requires a committed provider who is willing to transfer a complete production process, and not just the formulation and fill-finish parts of the process. It requires a recipient with established experience in vaccine production for human use and the ability to conduct research into new developments. In addition, the country of the recipient should preferably have sufficient financial resources to support the undertaking, and an internal market for the new vaccine. Technology transfer should create a solid partnership that results in the joint development of new competency, improvements to the product, and to further innovation. The Instituto Butantan-sanofi pasteur partnership can be seen as a model for successful technology transfer and has led to the technological independence of the Instituto Butantan in the use a strategic public health tool.
Bloom, H G; Bloom, J S; Krasnoff, L; Frank, A D
This study compared three interventions designed to increase acceptance of influenza and pneumococcal vaccines among elderly hospitalized patients. All individuals 65 and older able to give informed consent (73 patients) who were admitted to one medical floor of an acute care hospital were randomized to one of three groups. All groups received informational pamphlets explaining influenza and pneumococcal disease, their respective vaccines, and indications for their use. The first group received pamphlets only, the second received nursing follow-up, and the third received trained volunteer follow-up. Patients on another medical floor served as controls. The results showed a significant improvement in vaccine acceptance in all three study groups compared to controls for both influenza (78% vs 0%) and pneumococcal (75% vs 0%) vaccines. The differences among the three groups were not significant. No significant differences were found among patients accepting or refusing vaccination with regard to diagnosis, age, length of stay, sex, or having a private physician. We conclude that a simple educational program followed by offering vaccination before hospital discharge can be easily implemented, and dramatically increase immunization rates in this high risk group.
Clegg, Christopher H; Roque, Richard; Perrone, Lucy A; Rininger, Joseph A; Bowen, Richard; Reed, Steven G
The ongoing threat from Influenza necessitates the development of new vaccine and adjuvant technologies that can maximize vaccine immunogenicity, shorten production cycles, and increase global vaccine supply. Currently, the most successful adjuvants for Influenza vaccines are squalene-based oil-in-water emulsions. These adjuvants enhance seroprotective antibody titers to homologous and heterologous strains of virus, and augment a significant dose sparing activity that could improve vaccine manufacturing capacity. As an alternative to an emulsion, we tested a simple lipid-based aqueous formulation containing a synthetic TLR4 ligand (GLA-AF) for its ability to enhance protection against H5N1 infection. GLA-AF was very effective in adjuvanting recombinant H5 hemagglutinin antigen (rH5) in mice and was as potent as the stable emulsion, SE. Both adjuvants induced similar antibody titers using a sub-microgram dose of rH5, and both conferred complete protection against a highly pathogenic H5N1 challenge. However, GLA-AF was the superior adjuvant in ferrets. GLA-AF stimulated a broader antibody response than SE after both the prime and boost immunization with rH5, and ferrets were better protected against homologous and heterologous strains of H5N1 virus. Thus, GLA-AF is a potent emulsion-free adjuvant that warrants consideration for pandemic influenza vaccine development.
We evaluated protection conferred by mucosal vaccination with replication competent adenovirus (RCA)-free recombinant adenovirus expressing a codon-optimized avian influenza (AI) H5 gene (AdTW68.H5ck). Commercial layer-type chicken groups were singly vaccinated ocularly at 5 days of age, or singly v...
A comprehensive review of avian influenza (AI) control methods has been completed. From 2002-2010, over 113 billion doses of AI vaccine were used in poultry in 15 countries. The majority of vaccine (over 90%) was used in China while significant amounts were used in Egypt, Indonesia, and Vietnam. ...
more seasonal vaccine than any other country, some stakeholders told us that low vaccination rates can decrease incentives for manufacturers to...of U.S.-Licensed Manufacturers of Seasonal Influenza Vaccine and Number of Doses Produced and Distributed for the 2000–01 through 2010–11 Influenza... Seasons 24 Table 7: Influenza Vaccine Production Process Using Egg-Based Technology 38 Table 8: Additional Potential Benefits of Adjuvants 43
As Product Development Partnerships (PDPs) emerge and evolve in response to the need for vaccines, this paper re-examines the oldest and most successful PDP in the vaccine field; that which year after year, produces and reinvents influenza vaccines. This paper describes the influenza vaccine production and innovation system and reviews some of its most recent major innovations. Innovation in this system is a result of collaborative partnerships between various actors from both the public and private sector. It is argued that the influenza vaccine innovation system is a Product Development Partnership (PDP), be it an unconventional one, with a central coordination role allocated to the WHO rather than a private company or charitable/not for profit entity. The unusual structure of this PDP overcomes some of the organizational issues surrounding vaccine research and production faced by other documented PDPs. These are first, the need to coordinate knowledge flow via an effective knowledge broker. Second, the need to build in-house capacity and fund essential research and elements of production where private partners find involvement too risky or costly.
Chan, Candice Yuen-Yue; Tambyah, Paul Anantharajah
Vaccination is the principal means to reduce the impact of influenza infection. Effective vaccination programs require a reliable and safe production system. Traditionally, influenza vaccines are produced in embryonated chicken eggs. Over the last two decades, new cell culture-derived vaccines have been licensed and manufactured, and other vaccines are still in various phases of development. Vero cells have been used for the development of a wide variety of vaccines including influenza vaccines. Pandemic and avian influenza vaccines derived from Vero cells have been shown to be well tolerated and immunogenic in animal and Phase I-II clinical studies. A Phase III randomized, double-blind, placebo-controlled trial of a trivalent influenza vaccine produced in Vero-cell culture was conducted in 7250 adults aged 18-49 years. Overall protective efficacy for antigenically matched influenza vaccine was 78.5%. The vaccine was well tolerated with no treatment-related serious adverse events and compared favorably with egg-derived vaccines from previous trials. Vero-cell-derived influenza vaccines have the potential to be an important parts of the influenza vaccine strategy, especially if an avian-derived strain becomes predominant or the demand outstrips the capacity of egg-based production systems.
Assessing the pandemic risk posed by specific non-human influenza A viruses remains a complex challenge. As influenza virus genome sequencing becomes cheaper, faster and more readily available, the ability to predict pandemic potential from sequence data could transform pandemic influenza risk asses...
Moore, Dorothy L
The Canadian Paediatric Society continues to encourage annual influenza vaccination for ALL children and youth ≥6 months of age. Recommendations from the National Advisory Committee on Immunization for the 2015/2016 influenza season include some important changes: Children and adolescents with neurological or neurodevelopmental disorders were added to the list of individuals considered to be at high risk for severe influenza.Quadrivalent influenza vaccines are recommended preferentially over trivalent vaccines for use in children and youth.An adjuvanted trivalent inactivated influenza vaccine is now available for use in children six to 23 months of age. PMID:26526862
Sullivan, Seth J; Jacobson, Robert; Poland, Gregory A
On 23 December 2009, the US FDA approved Fluzone® High Dose, a high-dose formulation of the trivalent inactivated influenza vaccine, for prevention of influenza in people 65 years of age and older. As it was approved via an accelerated process designed to allow expeditious availability of safe and effective products with promise to treat or prevent serious or life-threatening diseases, the manufacturer is required to conduct further studies to demonstrate effectiveness. Although these studies are underway, a recently completed randomized, controlled trial demonstrated that this vaccine, containing four-times more hemagglutinin than standard-dose inactivated influenza vaccines, can produce an enhanced immunologic response in subjects of 65 years of age and older, while maintaining a favorable safety profile. This article introduces the vaccine, presents currently available safety and immunogenicity data, discusses current recommendations for use, and proposes what we can expect in the coming years.
Montomoli, Emanuele; Khadang, Baharak; Piccirella, Simona; Trombetta, Claudia; Mennitto, Elisa; Manini, Ilaria; Stanzani, Valerio; Lapini, Giulia
In the 20th century, three influenza pandemics killed approximately 100 million people. The traditional method of influenza vaccine manufacturing is based on using chicken eggs. However, the necessity of the availability of millions of fertile eggs in the event of a pandemic has led research to focus on the development of cell culture-derived vaccines, which offer shorter lead-in times and greater flexibility of production. So far, the cell substrates being evaluated and in use include Vero, Madin-Darby canine kidney, PER.C6 and insect cells. However, Vero cells are the most widely accepted among others. This review introduces briefly the concepts of advanced cell culture-derived influenza vaccine production and highlights the advantages of these vaccines in terms of efficiency, speed and immunogenicity based on the clinical data obtained from different studies.
... Biological Products for Swine Influenza Vaccines AGENCY: National Institutes of Health, Public Health Service... methods of use as Veterinary Influenza Vaccines. Sustained outbreaks of highly pathogenic influenza in animals increase the risk of reassortment and adaption to humans. This technology describes DNA...
Peltola, Heikki; Pelkonen, Tuula; Bernardino, Luis; Monteiro, Lurdes; Silvestre, Silvia da Conceição; Anjos, Elizabete; Cruzeiro, Manuel Leite; Pitkäranta, Anne; Roine, Irmeli
In Angola during 2003-2012, we detected Haemophilus influenzae in 18% of 2,634 and 26% of 2,996 bacteriologically positive pleural or cerebrospinal fluid samples, respectively, from children. After vaccination launch in 2006, H. influenzae empyema declined by 83% and meningitis by 86%. Severe H. influenzae pneumonia and meningitis are preventable by vaccination.
Francisco, Priscila Maria Stolses Bergamo; Borim, Flávia Silva Arbex; Neri, Anita Liberalesso
The vaccine against influenza is the main preventative intervention in public health for this disease. The aim of this study was to establish the prevalence of influenza vaccination in senior citizens according to indicators for their functional capacity, frailty, social support and involvement and state of health. This cross-sectional study was conducted in Campinas in 2008-2009 (FIBRA network, Unicamp center) with a probability sampling of the elderly population(≥ 65 years old).The dependent variable was immunization against influenza in the twelve months prior to the research. The adjusted prevalence ratios were estimated by means of Poisson multiple regression analysis. Of the six hundred and seventy-nine senior citizens involved, 74.4% stated they had been vaccinated during the previous year. The prevalence of the vaccination was significantly higher among men and lower among those with a higher level of education. Slow gait speed is positively associated with immunization, as are most of the social involvement indicators. This can contribute towards improving immunization adherence against seasonal influenza and should be widely acknowledged in order to broaden immunization coverage in Campinas.
Shropshire, Ali M.; Brent-Hotchkiss, Renee; Andrews, Urkovia K.
Objective: To describe the effectiveness of a mass media campaign in increasing the rate of college student influenza vaccine obtainment. Participants/Methods: Students ("N" = 721) at a large southern university completed a survey between September 2011 and January 2012 assessing what flu clinic media sources were visualized and if they…
characterization capabilities within the DoD • Culture, HAI , PCR (battery), Sequencing, Serology (HI, MN) – Rapid sharing of results with CDC and/or...unspecified vaccination types Collect 2 Swabs from Each Pt with “Influenza-Like Illness” (ILI) Follow DoD case definition for ILI: • FEVER ≥100.5°F
Alberta-Wszolek, Lauren; Mousette, Alyse M; Mahalingam, Meera; Levin, Nikki A
Linear IgA Bullous Dermatosis (LABD) is an immune-mediated subepidermal vesiculobullous eruption characterized by linear deposits of IgA at the basement membrane zone. Most cases are idiopathic but medications, infections, and malignancies have also been reported to induce LABD. We report the case of a 54-year-old woman who developed LABD shortly after receiving an influenza vaccination.
Laguio-Vila, Maryrose R.; Thompson, Mark G.; Reynolds, Sue; Spencer, Sarah M.; Gaglani, Manjusha; Naleway, Allison; Ball, Sarah; Bozeman, Sam; Baker, Steven; Martínez-Sobrido, Luis; Levine, Min; Katz, Jackie; Fry, Alicia M.; Treanor, John J.
Background. Most inactivated influenza vaccines contain purified and standardized hemagglutinin (HA) and residual neuraminidase (NA) antigens. Vaccine-associated HA antibody responses (hemagglutination inhibition [HAI]) are well described, but less is known about the immune response to the NA. Methods. Serum of 1349 healthcare personnel (HCP) electing or declining the 2010–2011 trivalent-inactivated influenza vaccine ([IIV3], containing A/California/7/2009 p(H1N1), A/Perth/16/2009 [H3N2], B/Brisbane/60/2008 strains) were tested for NA-inhibiting (NAI) antibody by a modified lectin-based assay using pseudotyped N1 and N2 influenza A viruses with an irrelevant (H5) HA. Neuraminidase-inhibiting and HAI antibody titers were evaluated approximately 30 days after vaccination and end-of-season for those with polymerase chain reaction (PCR)-confirmed influenza infection. Results. In 916 HCP (68%) receiving IIV3, a 2-fold increase in N1 and N2 NAI antibody occurred in 63.7% and 47.3%, respectively. Smaller responses occurred in HCP age >50 years and those without prior 2009–2010 IIV3 nor monovalent A(H1N1)pdm09 influenza vaccinations. Forty-four PCR-confirmed influenza infections were observed, primarily affecting those with lower pre-exposure HAI and NAI antibodies. Higher pre-NAI titers correlated with shorter duration of illness for A(H1N1)pdm09 virus infections. Conclusions. Trivalent-inactivated influenza vaccine is modestly immunogenic for N1 and N2 antigens in HCP. Vaccines eliciting robust NA immune responses may improve efficacy and reduce influenza-associated morbidity. PMID:25884004
Inactivated influenza vaccines do not provide cross-protection to diverse antigenic strains that could be circulating or suddenly arise in a population. It is desirable to vaccinate at a young age to provide maximum protection from influenza; however, maternally-derived factors (antibody or cells) c...
Recently, a new avian influenza vaccine was licensed by USDA for use in the United States for protection of commercial poultry. The vaccine is a recombinant herpes virus of turkeys expressing the hemagglutinin gene of an H5 subtype avian influenza virus belonging to the 2.2 clade of the H5N1 highly ...
Subramanian, Rahul; Graham, Andrea L.; Grenfell, Bryan T.; Arinaminpathy, Nimalan
Despite the availability of vaccines, influenza remains a major public health challenge. A key reason is the virus capacity for immune escape: ongoing evolution allows the continual circulation of seasonal influenza, while novel influenza viruses invade the human population to cause a pandemic every few decades. Current vaccines have to be updated continually to keep up to date with this antigenic change, but emerging ‘universal’ vaccines—targeting more conserved components of the influenza virus—offer the potential to act across all influenza A strains and subtypes. Influenza vaccination programmes around the world are steadily increasing in their population coverage. In future, how might intensive, routine immunization with novel vaccines compare against similar mass programmes utilizing conventional vaccines? Specifically, how might novel and conventional vaccines compare, in terms of cumulative incidence and rates of antigenic evolution of seasonal influenza? What are their potential implications for the impact of pandemic emergence? Here we present a new mathematical model, capturing both transmission dynamics and antigenic evolution of influenza in a simple framework, to explore these questions. We find that, even when matched by per-dose efficacy, universal vaccines could dampen population-level transmission over several seasons to a greater extent than conventional vaccines. Moreover, by lowering opportunities for cross-protective immunity in the population, conventional vaccines could allow the increased spread of a novel pandemic strain. Conversely, universal vaccines could mitigate both seasonal and pandemic spread. However, where it is not possible to maintain annual, intensive vaccination coverage, the duration and breadth of immunity raised by universal vaccines are critical determinants of their performance relative to conventional vaccines. In future, conventional and novel vaccines are likely to play complementary roles in vaccination
Gicquelais, Rachel E.; Safi, Haytham; Butler, Sandra; Smith, Nathaniel; Haselow, Dirk T.
Background: Influenza is a major cause of seasonal viral respiratory illness among school-aged children. Accordingly, the Arkansas Department of Health (ADH) coordinates >800 school-based influenza immunization clinics before each influenza season. We quantified the relationship between student influenza vaccination in Arkansas public schools…
Cheng, Allen C; Brown, Simon; Waterer, Grant; Holmes, Mark; Senenayake, Sanjaya; Friedman, N Deborah; Hewagama, Saliya; Simpson, Graham; Wark, Peter; Upham, John; Korman, Tony; Dwyer, Dominic; Wood-Baker, Richard; Irving, Louis; Bowler, Simon; Kotsimbos, Tom; Kelly, Paul
Influenza is mostly a mild, self-limiting infection and severe infection requiring hospitalisation is uncommon. Immunisation aims to reduce serious morbidity and mortality. The Influenza Complications Alert Network (FluCAN) is a sentinel hospital-based surveillance program that operates at 15 sites across all states and territories in Australia. This study reports on the epidemiology of hospitalisation with confirmed influenza, estimate vaccine coverage and influenza vaccine protection against hospitalisation with influenza during the 2012 influenza season. In this observational study, cases were defined as patients admitted to one of the sentinel hospitals with influenza confirmed by nucleic acid detection. Controls were patients who had acute respiratory illnesses who were test-negative for influenza. Vaccine effectiveness was estimated as 1 minus the odds ratio of vaccination in case patients compared with control patients, after adjusting for known confounders. During the period 9 April to 31 October 2012, 1,231 patients were admitted with confirmed influenza at the 15 FluCAN sentinel hospitals. Of these, 47% were more than 65 years of age, 8% were Indigenous Australians, 3% were pregnant and 76% had chronic co-morbidities. Influenza A was detected in 83% of patients. Vaccination coverage was calculated from the vaccination status of 1,216 test negative controls and was estimated at 77% in patients 65 years or over and 61% in patients with chronic comorbidities. Vaccination effectiveness was estimated at 41% (95% CI: 28%, 51%, P<0.001). Vaccine coverage was incomplete in at-risk groups, particularly non-elderly patients with medical comorbidities. The study results suggest that the seasonal influenza vaccine was moderately protective against hospitalisation with influenza during the 2012 season.
Lopez, A M; Hecker, R; Mutwiri, G; van Drunen Littel-van den Hurk, S; Babiuk, L A; Townsend, H G G
Previous studies have shown that protection against equine influenza virus (EIV) is partially mediated by virus-specific IgGa and IgGb. In this study we tested whether addition of a CpG ODN formulation to a commercial killed virus vaccine would enhance EIV-specific IgGa and IgGb antibody responses, and improve protection against an experimental EIV challenge. Thirty naïve horses were assigned to one of three groups and vaccinated as follows: 10 were given vaccine (Encevac TC4, Intervet Inc.) alone, 10 were given vaccine plus 0.25 mg CpG ODN 2007 formulated with 30% Emulsigen (CpG/Em), and 10 controls were given saline. All horses were challenged with live virus 12 weeks after the final vaccination. Antibody responses were tested by single radial hemolysis (SRH) and ELISA, and protection was evaluated by determination of temperature, coughing, and clinical scores. Killed virus vaccine combined with CpG/Em induced significantly greater serologic responses than did the vaccine alone. All antibody isotypes tested increased after the addition of CpG/Em, although no shift in relative antibody isotypes concentrations was detected. Vaccination significantly improved protection against challenge but the differences between the two vaccine groups were not statistically significant. This study is the first demonstration that CpG/Em enhances antigen-specific antibody responses in horses and supports its potential to be used as an adjuvant for vaccines against equine infections.
Heikkinen, Terho; Booy, Robert; Campins, Magda; Finn, Adam; Olcén, Per; Peltola, Heikki; Rodrigo, Carlos; Schmitt, Heinz-Josef; Schumacher, Fabian; Teo, Stephen; Weil-Olivier, Catherine
Influenza is often regarded as an illness of the elderly portion of the population because most of the excess mortality associated with influenza epidemics occurs in that age group. However, evidence derived from a large number of clinical studies carried out in different countries and various settings has clearly demonstrated that the burden of influenza is also substantial in children. The attack rates of influenza during annual epidemics are consistently highest in children, and young children are hospitalized for influenza-related illnesses at rates comparable to those for adults with high-risk conditions. Especially among children younger than 3 years of age, influenza frequently predisposes the patient to bacterial complications such as acute otitis media. Children also serve as the main transmitters of influenza in the community. A safe and effective vaccine against influenza has been available for decades, but the vaccine is rarely used even for children with high-risk conditions. Despite several existing problems related to influenza vaccination of children, the current evidence indicates that the advantages of vaccinating young children would clearly outweigh the disadvantages. Considering the total burden of influenza in children, children younger than 3 years of age should be regarded as a high-risk group for influenza, analogously with the age-based definition of high risk among persons 65 years of age or older. Annual influenza vaccination should be recommended to all children from 6 months to 3 years of age.
Chang, Yu-Chia; Tung, Ho-Jui; Hsu, Shang-Wei; Chen, Lei-Shin; Kung, Pei-Tseng; Huang, Kuang-Hua; Chiou, Shang-Jyh; Tsai, Wen-Chen
Background Influenza immunization among elderly people with disabilities is a critical public health concern; however, few studies have examined the factors associated with vaccination rates in non-Western societies. Methods By linking the National Disability Registration System and health service claims dataset from the National Health Insurance program, this population-based study investigated the seasonal influenza vaccination rate among elderly people with disabilities in Taiwan (N = 283,172) in 2008. A multivariate logistic regression analysis was conducted to adjust for covariates. Results Nationally, only 32.7% of Taiwanese elderly people with disabilities received influenza vaccination. The strongest predictor for getting vaccinated among older Taiwanese people with disabilities was their experience of receiving an influenza vaccination in the previous year (adjusted odds ratio [AOR] = 6.80, 95% confidence interval [CI]: 6.67–6.93). Frequent OPD use (AOR = 1.85, 95% CI: 1.81–1.89) and undergoing health examinations in the previous year (AOR = 1.66, 95% CI: 1.62–1.69) also showed a moderate and significant association with receiving an influenza vaccination. Conclusions Although free influenza vaccination has been provided in Taiwan since 2001, influenza immunization rates among elderly people with disabilities remain low. Policy initiatives are required to address the identified factors for improving influenza immunization rates among elderly people with disabilities. PMID:27336627
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
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.
The negative impact of high pathogenicity avian influenza virus (HPAIV) infection on egg production and deposition of virus in eggs, as well as any protective effect of vaccination, is unknown. Individually housed non-vaccinated, sham-vaccinated and inactivated H5N9 vaccinated once or twice adult Wh...
Chen, Chi-Yuan; Lin, Shih-Yeh; Cheng, Ming-Chu; Tsai, Ching-Ping; Hung, Chang-Lin; Lo, Kai-Wei; Hwang, Yung; Hu, Yu-Chen
Baculovirus simultaneously displaying and expressing the avian influenza virus (AIV) hemagglutinin (HA) protein can induce potent anti-HA humoral and cellular immune responses. Based on the hypothesis that improving the antigen expression and presentation can further boost the AIV vaccine efficacies, we first constructed a baculoviral vector (Bac-HAW) with HA gene fused with the woodchuck hepatitis virus post-transcriptional regulatory element (WPRE) near its 3' end and expressed under the control of the hybrid CAG promoter. The WPRE fusion improved the HA expression and augmented the humoral and Th1 cellular immune responses after intramuscular administration into BALB/c mice. With Bac-HAW as the backbone, we next constructed Bac-HAMW which harbored the HA gene flanked with the signal sequence (MHCIss) and trafficking domain (MITD) of MHC class I molecule. In comparison with Bac-HAW, Bac-HAMW ameliorated the HA peptide presentation, significantly elevated the HA-specific humoral response (total IgG, IgG2a and hemagglutination inhibition titers) and favorably boosted the Th1 and IFN-γ(+)/CD8(+) T cell responses without extraneous adjuvants. These data collectively confirmed that enhancement of antigen expression and presentation by combining the WPRE and MHCIss/MITD fusion can potentiate the immunogenicity of the baculovirus-based vaccine, and implicates the potential of Bac-HAMW as an appealing AIV vaccine.
Furman, David; Jojic, Vladimir; Kidd, Brian; Shen-Orr, Shai; Price, Jordan; Jarrell, Justin; Tse, Tiffany; Huang, Huang; Lund, Peder; Maecker, Holden T; Utz, Paul J; Dekker, Cornelia L; Koller, Daphne; Davis, Mark M
Despite the importance of the immune system in many diseases, there are currently no objective benchmarks of immunological health. In an effort to identifying such markers, we used influenza vaccination in 30 young (20–30 years) and 59 older subjects (60 to >89 years) as models for strong and weak immune responses, respectively, and assayed their serological responses to influenza strains as well as a wide variety of other parameters, including gene expression, antibodies to hemagglutinin peptides, serum cytokines, cell subset phenotypes and in vitro cytokine stimulation. Using machine learning, we identified nine variables that predict the antibody response with 84% accuracy. Two of these variables are involved in apoptosis, which positively associated with the response to vaccination and was confirmed to be a contributor to vaccine responsiveness in mice. The identification of these biomarkers provides new insights into what immune features may be most important for immune health. PMID:23591775
Zhang, Yan-Yang; Tang, Xue-Feng; Du, Chang-Hui; Wang, Bin-Bing; Bi, Zhen-Wang; Dong, Bi-Rong
ABSTRACT The purpose of this study was to perform a meta-analysis comparing the effectiveness of influenza vaccination alone versus influenza plus pneumococcal dual vaccination for the prevention of pneumonia and mortality in adults ≥ 65 years of age. Medline, Cochrane, CENTRAL, EMBASE, and Google Scholar databases were searched. Inclusion criteria were: 1) Randomized controlled trials (RCTs), 2-arm prospective studies, or retrospective cohort studies; 2) Patients were ≥ 65 years of age with or without chronic respiratory disease; 3) Patients received the influenza vaccine alone or dual pneumococcal and influenza vaccination; 4) Results included incidence of recurrent respiratory tract infections, length of hospital stay, and overall mortality rate. The outcomes were pneumonia and all-cause mortality rates. Of 142 studies identified in the database searches, 6 were ultimately included in the systematic review, and 5 were included in meta-analysis. The number of patients that received the influenza vaccination alone ranged from 211 to 29,346 (total = 53,107), and the number that received influenza+pneumococcal vaccination ranged from 246 to 72,107 (total = 102,068). Influenza+pneumococcal vaccination was associated with a significantly lower pneumonia rate than influenza vaccination alone (relative risk [RR] = 0.835, 95% confidence interval [CI]: 0.718–0.971, P = 0.019), and with a significantly lower all-cause mortality rate than influenza vaccination alone (relative risk [RR] = 0.771, 95% confidence interval [CI]: 0.707–0.842, P = 0.001). In conclusion, the results of this study support concomitant pneumococcal and influenza vaccination of the elderly as a dual vaccination strategy is associated with lower pneumonia and all-cause mortality rates. PMID:27629584
Ibuka, Yoko; Ohkusa, Yasushi; Sugawara, Tamie; Chapman, Gretchen B; Yamin, Dan; Atkins, Katherine E; Taniguchi, Kiyosu; Okabe, Nobuhiko; Galvani, Alison P
Background Contact patterns and vaccination decisions are fundamental to transmission dynamics of infectious diseases. We report on age-specific contact patterns in Japan and their effect on influenza vaccination behaviour. Methods Japanese adults (N=3146) were surveyed in Spring 2011 to assess the number of their social contacts within a 24 h period, defined as face-to-face conversations within 2 m, and gain insight into their influenza-related behaviour. We analysed the duration and location of contacts according to age. Additionally, we analysed the probability of vaccination and influenza infection in relation to the number of contacts controlling for individual's characteristics. Results The mean and median reported numbers of daily contacts were 15.3 and 12.0, respectively. School-aged children and young adults reported the greatest number of daily contacts, and individuals had the most contacts with those in the same age group. The age-specific contact patterns were different between men and women, and differed between weekdays and weekends. Children had fewer contacts between the same age groups during weekends than during weekdays, due to reduced contacts at school. The probability of vaccination increased with the number of contacts, controlling for age and household size. Influenza infection among unvaccinated individuals was higher than for those vaccinated, and increased with the number of contacts. Conclusions Contact patterns in Japan are age and gender specific. These contact patterns, as well as their interplay with vaccination decisions and infection risks, can help inform the parameterisation of mathematical models of disease transmission and the design of public health policies, to control disease transmission. PMID:26424846
Hovden, Arnt-Ove; Cox, Rebecca Jane; Haaheim, Lars Reinhardt
Influenza is a major respiratory pathogen, which exerts a huge human and economic toll on society. Influenza is a vaccine preventable disease, however, the vaccine strains must be annually updated due to the continuous antigenic changes in the virus. Inactivated influenza vaccines have been used for over 50 years and have an excellent safety record. Annual vaccination is therefore recommended for all individuals with serious medical conditions, like COPD, and protects the vaccinee against influenza illness and also against hospitalization and death. In COPD patients, influenza infection can lead to exacerbations resulting in reduced quality of life, hospitalization and death in the most severe cases. Although there is only limited literature on the use of influenza vaccination solely in COPD patients, there is clearly enough evidence to recommend annual vaccination in this group. This review will focus on influenza virus and prophylaxis with inactivated influenza vaccines in COPD patients and other “at risk” groups to reduce morbidity, save lives, and reduce health care costs. PMID:18229561
... Swine Influenza Vaccine, RNA AGENCY: Animal and Plant Health Inspection Service, USDA. ACTION: Notice... test, an unlicensed Swine Influenza Vaccine, RNA. The environmental assessment, which is based on a risk analysis prepared to assess the risks associated with the field testing of this vaccine,...
Alfred, Norma J.; Turner, James C.; David, Felicita; DeLozier, David M.; Strikas, Raymond A.
The United States experienced a shortage of influenza vaccine for the 2004-2005 influenza season. The authors surveyed college health programs to determine whether they had targeted vaccine to priority groups and knew how to reallocate remaining vaccine. They used an electronic message to distribute a Web-based survey to the members of 3…
Bulanov, V E; Ivanov, A V; Shostak, G R
Explore information about the incidence of employees of enterprises of the oil and gas industry with the influenza (SARS). The degree of influence of vaccination on the incidence of influenza, the number and structure of complications as a result of vaccination and their impact on efficiency. Evaluation of the cost-effectiveness of vaccination.
Vaccine associated enhanced respiratory disease (VAERD) has been described in pigs vaccinated with whole-inactivated influenza virus (WIV) following infection with heterologous influenza A virus (IAV). WIV vaccination elicits production of cross-reactive, non-neutralizing antibody to the challenge I...
Vaccine associated enhanced respiratory disease (VAERD) has been described in pigs vaccinated with whole-inactivated influenza virus (WIV) following infection with heterologous influenza A virus (IAV). WIV vaccination elicits production of non-neutralizing antibody that is cross-reactive to the chal...
Huston, Jane E.; Mekaru, Sumiko R.; Kluberg, Sheryl; Brownstein, John S.
Objectives The goal of the HealthMap Vaccine Finder is to provide a free, comprehensive, online service where users can search for locations that offer immunizations. In this article, we describe the data and systems underlying the HealthMap Vaccine Finder (HVF) and summarize the project’s first year of operations. Methods We collected data on vaccination services from a variety of providers for 2012–2013. Data are used to populate an online, public, searchable map. Results In its first year, HVF collected information from 1256 providers representing 46 381 locations. The public Web site received 625 124 visits during the 2012–2013 influenza vaccination season. Conclusions HVF is a unique tool that connects the public to vaccine providers in their communities. During the 2012–2013 influenza season, HVF experienced significant usage and was able to respond to user feedback with new features. PMID:25880945
An influenza pandemic will place an enormous strain on the world's vaccine production, distribution and administration systems. Following a pandemic declaration, industry's priority will be to deliver as much vaccine in as short a timeframe as possible. In respect to this challenge, manufacturers have successfully developed antigen-sparing strategies and significantly increased production capacity, with further growth planned assuming ongoing rising demand for seasonal vaccines. The combination of these factors has the potential to closer meet global needs for vaccine supply than ever before through increased availability of pandemic and pre-pandemic vaccines. The demonstration of cross-clade reactivity with H5N1 viruses makes the concept of pre-pandemic stockpiling and vaccination a reality for this subtype. Ensuring these vaccines are made available in a timely fashion to those who need them will present significant challenges. For local authorities, national governments and international organisations this means defining vaccine allocation and procurement processes as well as strengthening, and where necessary establishing, the critical health systems and infrastructure required for vaccine deployment. For vaccine producers this means addressing the technical and logistical issues associated with supply. This includes working with regulators to streamline key procedures, including generic labelling and batch release, while establishing flexibility in supply formats, including bulk and finished products, to maximise the speed of delivery. Similarly, the deployment of large quantities of vaccines in an emergency situation requires appropriate transport infrastructure and the distribution of associated medical supplies. As well as addressing these issues, specific consideration must be given to the logistics and storage aspects associated with stockpiling pre-pandemic vaccines. Finally, mutually agreed contractual arrangements between manufacturers and governments
Caini, Saverio; Andrade, Winston; Badur, Selim; Balmaseda, Angel; Barakat, Amal; Bella, Antonino; Bimohuen, Abderrahman; Brammer, Lynnette; Bresee, Joseph; Bruno, Alfredo; Castillo, Leticia; Ciblak, Meral A.; Clara, Alexey W.; Cohen, Cheryl; Cutter, Jeffery; Daouda, Coulibaly; de Lozano, Celina; De Mora, Domenica; Dorji, Kunzang; Emukule, Gideon O.; Fasce, Rodrigo A.; Feng, Luzhao; Ferreira de Almeida, Walquiria Aparecida; Guiomar, Raquel; Heraud, Jean-Michel; Holubka, Olha; Huang, Q. Sue; Kadjo, Herve A.; Kiyanbekova, Lyazzat; Kosasih, Herman; Kusznierz, Gabriela; Lara, Jenny; Li, Ming; Lopez, Liza; Mai Hoang, Phuong Vu; Pessanha Henriques, Cláudio Maierovitch; Matute, Maria Luisa; Mironenko, Alla; Moreno, Brechla; Mott, Joshua A.; Njouom, Richard; Nurhayati; Ospanova, Akerke; Owen, Rhonda; Pebody, Richard; Pennington, Kate; Puzelli, Simona; Quynh Le, Mai thi; Razanajatovo, Norosoa Harline; Rodrigues, Ana; Rudi, Juan Manuel; Tzer Pin Lin, Raymond; Venter, Marietjie; Vernet, Marie-Astrid; Wangchuk, Sonam; Yang, Juan; Yu, Hongjie; Zambon, Maria; Schellevis, François; Paget, John
Introduction Determining the optimal time to vaccinate is important for influenza vaccination programmes. Here, we assessed the temporal characteristics of influenza epidemics in the Northern and Southern hemispheres and in the tropics, and discuss their implications for vaccination programmes. Methods This was a retrospective analysis of surveillance data between 2000 and 2014 from the Global Influenza B Study database. The seasonal peak of influenza was defined as the week with the most reported cases (overall, A, and B) in the season. The duration of seasonal activity was assessed using the maximum proportion of influenza cases during three consecutive months and the minimum number of months with ≥80% of cases in the season. We also assessed whether co-circulation of A and B virus types affected the duration of influenza epidemics. Results 212 influenza seasons and 571,907 cases were included from 30 countries. In tropical countries, the seasonal influenza activity lasted longer and the peaks of influenza A and B coincided less frequently than in temperate countries. Temporal characteristics of influenza epidemics were heterogeneous in the tropics, with distinct seasonal epidemics observed only in some countries. Seasons with co-circulation of influenza A and B were longer than influenza A seasons, especially in the tropics. Discussion Our findings show that influenza seasonality is less well defined in the tropics than in temperate regions. This has important implications for vaccination programmes in these countries. High-quality influenza surveillance systems are needed in the tropics to enable decisions about when to vaccinate. PMID:27031105
Iqbal, Shahed; Li, Rongxia; Gargiullo, Paul; Vellozzi, Claudia
Some studies reported an increased risk of Guillain-Barré syndrome (GBS) within six weeks of influenza vaccination. It has also been suggested that this finding could have been confounded by influenza illnesses. We explored the complex relationship between influenza illness, influenza vaccination, and GBS, from an ecologic perspective using nationally representative data. We also studied seasonal patterns for GBS hospitalizations. Monthly hospitalization data (2000-2009) for GBS, and pneumonia and influenza (P&I) in the Nationwide Inpatient Sample were included. Seasonal influenza vaccination coverage for 2004-2005 through the 2008-2009 influenza seasons (August-May) was estimated from the National Health Interview Survey data. GBS seasonality was determined using Poisson regression. GBS and P&I temporal clusters were identified using scan statistics. The association between P&I and GBS hospitalizations in the same month (concurrent) or in the following month (lagged) were determined using negative binomial regression. Vaccine coverage increased over the years (from 19.7% during 2004-2005 to 35.5% during 2008-2009 season) but GBS hospitalization did not follow a similar pattern. Overall, a significant correlation between monthly P&I and GBS hospitalizations was observed (Spearman's correlation coefficient=0.7016, p<0.0001). A significant (p=0.001) cluster of P&I hospitalizations during December 2004-March 2005 overlapped a significant (p=0.001) cluster of GBS hospitalizations during January 2005-February 2005. After accounting for effects of monthly vaccine coverage and age, P&I hospitalization was significantly associated (p<0.0001) with GBS hospitalization in the concurrent month but not with GBS hospitalization in the following month. Monthly vaccine coverage was not associated with GBS hospitalization in adjusted models (both concurrent and lagged). GBS hospitalizations demonstrated a seasonal pattern with winter months having higher rates compared to the
Souza, Thiago Moreno L; Santini-Oliveira, Marilia; Martorelli, Andressa; Luz, Paula M; Vasconcellos, Mauricio T L; Giacoia-Gripp, Carmem B W; Morgado, Mariza; Nunes, Estevão P; Lemos, Alberto S; Ferreira, Ana C G; Moreira, Ronaldo I; Veloso, Valdiléa G; Siqueira, Marilda; Grinsztejn, Beatriz; Camacho, Luiz A B
HIV-infected individuals have a higher risk of serious illnesses following infection by infection with influenza. Although anti-influenza vaccination is recommended, immunosuppression may limit their response to active immunization. We followed-up a cohort of HIV-infected individuals vaccinated against influenza to assess the immunogenicity and sustainability of the immune response to vaccination. Individuals were vaccinated 2011 with inactivated triple influenza vaccine (TIV), and they had received in 2010 the monovalent anti-A(H1N1)pdm09 vaccine. The sustainability of the immune response to A(H1N1)pdm09 at 12 months after monovalent vaccination fell, both in individuals given two single or two double doses. For these individuals, A(H1N1)pdm09 component from TIV acted as a booster, raising around 40% the number of seroprotected individuals. Almost 70% of the HIV-infected individuals were already seroprotected to A/H3N2 at baseline. Again, TIV boosted over 90% the seroprotection to A/H3N2. Anti-A/H3N2 titers dropped by 20% at 6 months after vaccination. Pre-vaccination seroprotection rate to influenza B (victoria lineage) was the lowest among those tested, seroconversion rates were higher after vaccination. Seroconversion/protection after TIV vaccination did not differ significantly across categories of clinical and demographic variables. Anti-influenza responses in Brazilian HIV-infected individuals reflected both the previous history of virus circulation in Brazil and vaccination.
Swayne, David E
There are 30 recorded epizootics of H5 or H7 high pathogenicity avian influenza (HPAI) from 1959 to early 2012. The largest of these epizootics, affecting more birds and countries than the other 29 epizootics combined, has been the H5N1 HPAI, which began in Guangdong China in 1996, and has killed or resulted in culling of over 250 million poultry and/or wild birds in 63 countries. Most countries have used stamping-out programs in poultry to eradicate H5N1 HPAI. However, 15 affected countries have utilized vaccination as a part of the control strategy. Greater than 113 billion doses were used from 2002 to 2010. Five countries have utilized nationwide routine vaccination programs, which account for 99% of vaccine used: 1) China (90.9%), 2) Egypt (4.6%), 3) Indonesia (2.3%), 4) Vietnam (1.4%), and 5) Hong Kong Special Administrative Region (< 0.01%). Mongolia, Kazakhstan, France, The Netherlands, Cote d'Ivoire, Sudan, North Korea, Israel, Russia, and Pakistan used < 1% of the avian influenza (AI) vaccine, and the AI vaccine was targeted to either preventive or emergency vaccination programs. Inactivated AI vaccines have accounted for 95.5% of vaccine used, and live recombinant virus vaccines have accounted for 4.5% of vaccine used. The latter are primarily recombinant Newcastle disease vectored vaccine with H5 influenza gene insert. China, Indonesia, Egypt, and Vietnam implemented vaccination after H5N1 HPAI became enzootic in domestic poultry. Bangladesh and eastern India have enzootic H5N1 HPAI and have not used vaccination in their control programs. Clinical disease and mortality have been prevented in chickens, human cases have been reduced, and rural livelihoods and food security have been maintained by using vaccines during HPAI outbreaks. However, field outbreaks have occurred in vaccinating countries, primarily because of inadequate coverage in the target species, but vaccine failures have occurred following antigenic drift in field viruses within China, Egypt
Kang, Hee Sun; De Gagne, Jennie C; Kim, Jung-Hee
Following our study of attitudes, barriers, and intentions concerning the influenza vaccination among pregnant women in South Korea, we discovered that women displaying a more positive attitude toward the influenza vaccination were more likely to receive it during their pregnancy. We also found that attitudes toward vaccination were more positive among vaccinated pregnant women than among those who were unvaccinated. Furthermore, women showed a greater intention to get vaccinated if a clinician, rather than friends, recommended it. The major perceived barriers to receiving an influenza vaccination were being pregnant, fearing harm to the baby, feeling healthy, and thinking it is unnecessary.
Influenza A (H3N2) viruses were the predominant viruses isolated in the United States and worldwide during 1999-2000. This was the third consecutive year that influenza A/Sydney/05/97-like (H3N2) viruses were the most prevalent viruses isolated in the United States. Influenza activity in the United States was similar to the previous two seasons, although mortality measurements attributed to pneumonia and influenza (P&I) were unusually high. Overall, the 1999-2000 influenza vaccine was well matched to circulating influenza viruses. The 2000-01 influenza season will be the first for which influenza vaccination is recommended for all persons aged > or =50 years. This report summarizes surveillance for influenza in the United States and worldwide during the 1999-2000 influenza season, describes the composition of the 2000-01 influenza vaccine, and highlights changes in the recommendations for prevention and control of influenza.
Hensley, Scott E.
Seasonal influenza vaccine strains are routinely updated when influenza viruses acquire mutations in exposed regions of the hemagglutinin and neuraminidase glycoproteins. Ironically, although thousands of viral isolates are sequenced each year, today's influenza surveillance community places less emphasis on viral genetic information and more emphasis on classical serological assays when choosing vaccine strains. Here, I argue that these classical serological assays are oversimplified and that they fail to detect influenza mutations that facilitate escape of particular types of human antibodies. I propose that influenza vaccine strains should be updated more frequently even when classical serological assays fail to detect significant antigenic alterations. PMID:25108824
McAnerney, Johanna M; Walaza, Sibongile; Tempia, Stefano; Blumberg, Lucille; Treurnicht, Florette K; Madhi, Shabir A; Valley-Omar, Ziyaad; Cohen, Cheryl
Trivalent seasonal influenza vaccine effectiveness during the 2015 season in South Africa was assessed using a test-negative case control study design. Influenza A(H1N1)pdm09 was the dominant circulating strain. Overall influenza vaccine coverage was 3.2% (29/899). The vaccine effectiveness estimate, against any influenza virus infection, adjusted for age, underlying conditions and timing within season was 46.2% (95% CI: -23.5 to 76.5), and 53.6% (95% CI: -62.6 to 80.3) against influenza A(H1N1)pdm09.
Edwards, Frances; Masick, Kevin D; Armellino, Donna
Achieving high vaccination rates of health care personnel (HCP) is critical in preventing influenza transmission from HCP to patients and from patients to HCP; however, acceptance rates remain low. In 2013, New York State adopted the flu mask regulation, requiring unvaccinated HCP to wear a mask when in areas where patients are present. The purpose of this study assessed the impact of the flu mask regulation on the HCP influenza vaccination rate. A 13-question survey was distributed electronically and manually to the HCP to examine their knowledge of influenza transmission and the influenza vaccine and their personal vaccine acceptance history and perception about the use of the mask while working if not vaccinated. There were 1,905 respondents; 87% accepted the influenza vaccine, and 63% were first-time recipients who agreed the regulation influenced their vaccination decision. Of the respondents who declined the vaccine, 72% acknowledge HCP are at risk for transmitting influenza to patients, and 56% reported they did not receive enough information to make an educated decision. The flu mask protocol may have influenced HCP's choice to be vaccinated versus wearing a mask. The study findings supported that HCP may not have adequate knowledge on the morbidity and mortality associated with influenza. Regulatory agencies need to consider an alternative approach to increase HCP vaccination, such as mandating the influenza vaccine for HCP.
The influenza pandemic of 2009 demonstrated the inability of the established global capacity for egg-based vaccine production technology to provide sufficient vaccine for the population in a timely fashion. Several alternative technologies for developing influenza vaccines have been proposed, among which non-replicating virus-like particles (VLPs) represent an attractive option because of their safety and immunogenic characteristics. VLP vaccines against pandemic influenza have been developed in tobacco plant cells and in Sf9 insect cells infected with baculovirus that expresses protein genes from pandemic influenza strains. These technologies allow rapid and large-scale production of vaccines (3–12 weeks). The 2009 influenza outbreak provided an opportunity for clinical testing of a pandemic influenza VLP vaccine in the midst of the outbreak at its epicenter in Mexico. An influenza A(H1N1)2009 VLP pandemic vaccine (produced in insect cells) was tested in a phase II clinical trial involving 4,563 healthy adults. Results showed that the vaccine is safe and immunogenic despite high preexisting anti-A(H1N1)2009 antibody titers present in the population. The safety and immunogenicity profile presented by this pandemic VLP vaccine during the outbreak in Mexico suggests that VLP technology is a suitable alternative to current influenza vaccine technologies for producing pandemic and seasonal vaccines. PMID:22330956
Maroof, Asher; Yorgensen, Yvonne M.; Li, Yufeng; Evans, Jay T.
Influenza disease is a global health issue that causes significant morbidity and mortality through seasonal epidemics. Currently, inactivated influenza virus vaccines given intramuscularly or live attenuated influenza virus vaccines administered intranasally are the only approved options for vaccination against influenza virus in humans. We evaluated the efficacy of a synthetic toll-like receptor 4 agonist CRX-601 as an adjuvant for enhancing vaccine-induced protection against influenza infection. Intranasal administration of CRX-601 adjuvant combined with detergent split-influenza antigen (A/Uruguay/716/2007 (H3N2)) generated strong local and systemic immunity against co-administered influenza antigens while exhibiting high efficacy against two heterotypic influenza challenges. Intranasal vaccination with CRX-601 adjuvanted vaccines promoted antigen-specific IgG and IgA antibody responses and the generation of polyfunctional antigen-specific Th17 cells (CD4+IL-17A+TNFα+). Following challenge with influenza virus, vaccinated mice transiently exhibited increased weight loss and morbidity during early stages of disease but eventually controlled infection. This disease exacerbation following influenza infection in vaccinated mice was dependent on both the route of vaccination and the addition of the adjuvant. Neutralization of IL-17A confirmed a detrimental role for this cytokine during influenza infection. The expansion of vaccine-primed Th17 cells during influenza infection was also accompanied by an augmented lung neutrophilic response, which was partially responsible for mediating the increased morbidity. This discovery is of significance in the field of vaccinology, as it highlights the importance of both route of vaccination and adjuvant selection in vaccine development PMID:24465206
Wicker, S; Rabenau, H F; Gottschalk, R; Krause, G; McLennan, S
Despite decades of effort to encourage healthcare workers (HCWs) to be immunized against influenza, vaccination levels remain insufficient in Germany, with only one in five HCWs receiving the annual influenza vaccination. To prevent nosocomial influenza outbreaks and to ensure the protection of patients and HCWs, new approaches to increase vaccination rates are needed. The experience in the USA has shown that declination forms have increased vaccination coverage. One possible approach for Germany would be a combination of declination forms with the exclusive use of vaccinated staff in defined areas. This approach would respect a HCWs decision to refuse medical treatment, while at the same time protecting vulnerable patients. In addition, the influenza vaccination rates of HCWs should be collected in order to evaluate the implementation of vaccination policies. Similar to the setting of desired vaccination coverage for the chronically ill, a clearly defined vaccination goal should be established for HCWs.
Gany, Francesca; Rau-Murthy, Rohini; Mujawar, Imran
The Healthy People 2020 influenza immunization goal is 80% for non-institutionalized adults 18-64. However, vaccination rates remain stubbornly low. Culturally tailored approaches to communities with poor vaccine uptake are necessary. Taxi drivers are at risk for influenza and its complications, could serve as vectors for influenza infection, and could be an effective vaccination target to enhance herd immunity of the urban population. To the best of our knowledge, this is the first study related to influenza vaccination among taxi drivers. The NYC Taxi Network surveyed a convenience sample of 53 taxi drivers to understand vaccination barriers. Only 17% had been vaccinated. Results informed a pilot tailored workplace intervention, which resulted in vaccinations for 44% of unvaccinated drivers. The study revealed that older drivers were more likely to be vaccinated than younger drivers, while the most common barrier to immunization was that drivers thought vaccination was 'not necessary'.
Background Influenza vaccination coverage in medical students is usually low. Unlike health care workers, there is little information on the attitudes to and predictors of vaccination among medical students, and their attitudes towards institutional strategies for improving rates are unknown. Methods This cross-sectional study evaluated the effect of three influenza vaccination promotional strategies (Web page, video and tri-fold brochure) on medical students’ intention to get vaccinated and associated factors. A total of 538 medical students were asked to answer an anonymous questionnaire assessing the intention to get vaccinated after exposure to any of the promotional strategies. Sociodemographic data collected included: sex, age, university year, influenza risk group and cohabiting with member of a risk group. Results Four hundred twenty-one students answered the questionnaire, of whom 312 (74.1%) were female, 113 (26.8%) had done clinical rotations, and 111 (26.6%) reported intention to get the flu shot. Logistic regression showed the web group had a greater intention to get vaccinated than the reference group (OR: 2.42 95% CI: 1.16-5.03). Having done clinical rotations (OR: 2.55 95% CI: 1.36-4.38) and having received the shot in previous flu seasons (OR: 13.69 95% CI: 7.86-23.96) were independently associated with the intention to get vaccinated. Conclusion Given that previous vaccination is a factor associated with the intention to get vaccinated, education on vaccination of health care workers should begin while they are students, thereby potentiating the habit. In addition, the intention to get vaccinated was greater during the clinical phase of the university career, suggesting this is a good time to introduce promotion strategies. Online promotional campaigns, such as a thematic Web to promote vaccination of health workers, could improve the intention to get vaccinated. PMID:23866902
Rodriguez de Azero, M
Seasonal influenza is widely regarded as a continuing threat to public health, with vaccination remaining the principal measure of prophylaxis. In 2003, the World Health Organization issued targets for influenza vaccine coverage in the elderly of at least 50% by 2006 and 75% by 2010, endorsed by the European Parliament in two resolutions in 2005 and 2006. However, a number of European public health systems lack mechanisms to assess progress in influenza vaccine uptake. The European Vaccine Manufacturers group (EVM) undertook a Europe-wide survey of vaccine distribution over the last five seasons (between 2003 and 2008) to provide baseline data from which vaccination trends may be extrapolated. The survey data showed that the dose distribution level per capita in the 27 EU countries increased from 17% in 2003-4 to 20% in 2006-7; this growth was not maintained in the season 2007-8. Even without information on which age or risk groups received the vaccine, an immunisation rate of approximately 20% of the whole population falls short of the public health goal by more than half: an estimated 49% of the total population fall into risk groups recommended to receive the influenza vaccine in Europe. These data provide the only systematic review of vaccine dose distribution across Europe from a uniform source. Although they represent an important baseline parameter, age- and risk-group related vaccine uptake data with sufficient detail are needed to assist public health policy decision making, immunisation planning and monitoring. In light of this situation, and to support the improvement of immunisation rates across the EU, EVM aims to provide dose distribution data for each influenza season to assist Member States in the implementation of local immunisation policies.
Newall, Anthony T; Dehollain, Juan Pablo
It is important to consider the value for money offered by existing elderly influenza vaccination programs, particularly as doubts persist about the magnitude of the effectiveness of such programs. An informative approach to explore the value of vaccination is to consider what vaccine efficacy would be required for a program to be considered cost-effective. To estimate the cost-effectiveness of the current elderly (65+ years) influenza vaccination program in Australia, we modelled how the hypothetical removal of vaccination would increase current disease burden estimates depending on alternative vaccine efficacy assumptions. The base-case results of the analysis found that the existing elderly vaccination program is likely to be cost-effective (under A$50,000 per quality-adjusted life year gained) if the vaccine efficacy is above ∼30%. This study offers reassurance that the influenza vaccination of elderly Australians is likely to offer value for money.
Lone, Nazir I; Kavanagh, Kimberley; Robertson, Chris; McMenamin, Jim; von Wissmann, Beatrix; Vasileiou, Eleftheria; Butler, Chris; Ritchie, Lewis D; Gunson, Rory; Schwarze, Jürgen; Sheikh, Aziz
Introduction Seasonal (inactivated) influenza vaccination is recommended for all individuals aged 65+ and in individuals under 65 who are at an increased risk of complications of influenza infection, for example, people with asthma. Live attenuated influenza vaccine (LAIV) was recommended for children as they are thought to be responsible for much of the transmission of influenza to the populations at risk of serious complications from influenza. A phased roll-out of the LAIV pilot programme began in 2013/2014. There is limited evidence for vaccine effectiveness (VE) in the populations targeted for influenza vaccination. The aim of this study is to examine the safety and effectiveness of the live attenuated seasonal influenza vaccine programme in children and the inactivated seasonal influenza vaccination programme among different age and at-risk groups of people. Methods and analysis Test negative and cohort study designs will be used to estimate VE. A primary care database covering 1.25 million people in Scotland for the period 2000/2001 to 2015/2016 will be linked to the Scottish Immunisation Recall Service (SIRS), Health Protection Scotland virology database, admissions to Scottish hospitals and the Scottish death register. Vaccination status (including LAIV uptake) will be determined from the primary care and SIRS database. The primary outcome will be influenza-positive real-time PCR tests carried out in sentinel general practices and other healthcare settings. Secondary outcomes include influenza-like illness and asthma-related general practice consultations, hospitalisations and death. An instrumental variable analysis will be carried out to account for confounding. Self-controlled study designs will be used to estimate the risk of adverse events associated with influenza vaccination. Ethics and dissemination We obtained approval from the National Research Ethics Service Committee, West Midlands—Edgbaston. The study findings will be presented at
Mandelboim, Michal; Glatman-Freedman, Aharona; Drori, Yaron; Sherbany, Hilda; Pando, Rakefet; Sefty, Hanna; Zadka, Hila; Shohat, Tamar; Keller, Nathan; Mendelson, Ella
The seasonal influenza vaccine is currently the most effective preventive modality against influenza infection. Nasopharyngeal samples of vaccinated and non-vaccinated patients presenting with Influenza-like-illness (ILI) were collected from over 20 outpatient clinics located in different geographic parts of Israel and were tested for the presence of influenza viruses (influenza A and influenza B). Here we show, that in the 2014-2015 season, the vaccine that included the A/Texas/50/2012 H3N2 virus was ineffective. Significant numbers of individuals vaccinated with the 2014-2015 vaccine, of all ages, were infected with influenza A (H3N2), manifesting similar symptoms as the non-vaccinated group. We further demonstrate that the Israeli circulating influenza A(H3N2) virus was different than that included in the 2014-2015 northern hemisphere vaccine, and that antibodies elicited by this vaccine were significantly less efficient in neutralizing influenza A(H3N2) infection. PMID:26716420
Basta, Nicole E; Chao, Dennis L; Halloran, M Elizabeth; Matrajt, Laura; Longini, Ira M
Vaccinating school-aged children against influenza can reduce age-specific and population-level illness attack rates. Using a stochastic simulation model of influenza transmission, the authors assessed strategies for vaccinating children in the United States, varying the vaccine type, coverage level, and reproductive number R (average number of secondary cases produced by a typical primary case). Results indicated that vaccinating children can substantially reduce population-level illness attack rates over a wide range of scenarios. The greatest absolute reduction in influenza illness cases per season occurred at R values ranging from 1.2 to 1.6 for a given vaccine coverage level. The indirect, total, and overall effects of vaccinating children were strong when transmission intensity was low to intermediate. The indirect effects declined rapidly as transmission intensity increased. In a mild influenza season (R = 1.1), approximately 19 million influenza cases could be prevented by vaccinating 70% of children. At most, nearly 100 million cases of influenza illness could be prevented, depending on the proportion of children vaccinated and the transmission intensity. Given the current worldwide threat of novel influenza A (H1N1), with an estimated R of 1.4-1.6, health officials should consider strategies for vaccinating children against novel influenza A (H1N1) as well as seasonal influenza.
Ruiz, Jennifer; Gilleskie, Gary L; Brown, Patty; Burnett, Bruce; Carbonell, Ruben G
The critical need for enhancing influenza pandemic preparedness in many developing nations has led the World Health Organization (WHO) and the Biomedical Advanced Research and Development Authority (BARDA), part of the U.S. Department of Health and Human Services (HHS), to develop an international influenza vaccine capacity-building program. Among the critical limitations faced by many of these nations is lack of access to training programs for staff supporting operations within vaccine production facilities. With support from BARDA, the Biomanufacturing Training and Education Center (BTEC) at North Carolina State University has addressed this need for training by developing and delivering a comprehensive training program, consisting of three courses: Fundamentals of cGMP Influenza Vaccine Manufacturing, Advanced Upstream Processes for Influenza Vaccine Manufacturing, and Advanced Downstream Processes for Influenza Vaccine Manufacturing. The courses cover process design, transfer, and execution at manufacturing scale, quality systems, and regulations covering both manufacturing and approval of pandemic vaccines. The Fundamentals course focuses on the concepts, equipment, applicable regulations, and procedures commonly used to produce influenza vaccine. The two Advanced courses focus on process design, scale up, validation, and new technologies likely to improve efficiency of vaccine production. All three courses rely on a combination of classroom instruction and hands-on training in BTEC's various laboratories. Each course stands alone, and participants may take one or more of the three courses. Overall participant satisfaction with the courses has been high, and follow-up surveys show that participants actively transferred the knowledge they gained to the workplace. Future plans call for BTEC to continue offering the three courses and to create an online version of several modules of the Fundamentals course.
Surichan, Somchaiya; Wirachwong, Ponthip; Supachaturas, Wutichai; Utid, Kanchala; Theerasurakarn, Sompone; Langsanam, Pimsuk; Lakornrach, Pattharachai; Nitisaporn, Ladda; Chansikkakorn, Chanpen; Vangkanonta, Wilak; Kaweepornpoj, Ruangchai; Poopipatpol, Kittisak; Thirapakpoomanunt, Sit; Srichainak, Somchai; Artavatkun, Witit; Chokevivat, Vichai; Wibulpolprasert, Suwit
In 2005, a year after highly pathogenic avian influenza outbreaks in Thailand, the Thai Government issued a National Strategy Plan for Pandemic Influenza Preparedness, a major objective of which was the domestic production of seasonal influenza vaccine. It was considered that sustained influenza vaccine production was the best guarantee of a pandemic vaccine in the event of a future pandemic. The Government decided to provide funds to establish an industrial-scale influenza vaccine production plant, and gave responsibility for this challenging project to the Government Pharmaceutical Organization (GPO). In 2007, with support from the World Health Organization (WHO), the GPO started to develop egg-based, trivalent inactivated influenza vaccine (IIV) in a renovated pilot plant. In early 2009, during the second year of the project, the GPO turned its attention to develop a pandemic live attenuated influenza vaccine (PLAIV) against the influenza A (H1N1) virus. By December 2010, the H1N1 PLAIV had successfully completed Phase II clinical trials and was awaiting registration approval from the Thai Food and Drug Administration (TFDA). The GPO has also started to develop an H5N2 PLAIV, which is expected to enter clinical trials in January 2011. The next step in 2011 will be the development and clinical evaluation of seasonal LAIV. To meet the needs of the national seasonal influenza vaccination programme, the GPO aims to produce 2 million doses of trivalent IIV in 2012 and progressively increase production to the maximum annual capacity of 10 million doses. This article relates how influenza vaccine production capacity was developed and how major challenges are being met in an expeditious manner, with strong local and global commitment.
Parrella, Adriana; Gold, Michael; Marshall, Helen; Braunack-Mayer, Annette; Watson, Maureen; Baghurst, Peter
To assess parental vaccine safety views and future vaccination decisions after an adverse event following immunization (AEFI) experienced by their child. A cross-sectional telephone survey was conducted of parents of children aged 0-7 y, identified in AEFI reports submitted to the South Australian Immunization Section, Department Health. The reports included childhood National Immunization Program (NIP), seasonal or pandemic influenza vaccines. Interviews were conducted following a national suspension of the 2010 seasonal trivalent influenza (STIV) vaccine. Parental attitudes toward vaccine safety, reasons for reporting the AEFI and impact on future vaccination intent were assessed. Of 179 parents interviewed, 88% were confident in the safety of vaccines in general. Parents reporting an AEFI to the STIV were more likely to state the event had influenced future vaccination decisions than the NIP vaccine reporters (65% vs 14%, p < 0.001), with 63% stating refusal or hesitance to re-vaccinate their children against influenza. Media reports of the 2010 STIV program suspension was the most common reason for reporting an AEFI for parents of children who received an influenza vaccination. The AEFI experience did not impact on parental decision to continue with routine childhood NIP schedules, regardless of whether children received influenza or NIP vaccines. In contrast, most parents whose child experienced an AEFI to the 2010 STIV stated decreased confidence in the safety of influenza vaccines, which is likely to have impacted on the uptake of seasonal influenza vaccination in 2011. Addressing influenza vaccine safety concerns to promote influenza vaccination in the community is required.
Ren, Zhenghua; Lu, Zhongzheng; Wang, Lei; Huo, Zeren; Cui, Jianhua; Zheng, Tingting; Dai, Qing; Chen, Cuiling; Qin, Mengying; Chen, Meihua; Yang, Rirong
H9N2 subtype avian influenza viruses are widespread in domestic poultry, and vaccination remains the most effective way to protect the chicken population from avian influenza pandemics. Currently, egg-based H9N2 influenza vaccine production has several disadvantages and mammalian MDCK cells are being investigated as candidates for influenza vaccine production. However, little research has been conducted on low pathogenic avian influenza viruses (LPAIV) such as H9N2 replicating in mammalian cells using microcarrier beads in a bioreactor. In this study, we present a systematic analysis of a safe H9N2 influenza vaccine derived from MDCK cells for protecting chickens against influenza virus infection. In 2008, we isolated two novel H9N2 influenza viruses from chickens raised in southern China, and these H9N2 viruses were adapted to MDCK cells. The H9N2 virus was produced in MDCK cells in a scalable bioreactor, purified, inactivated, and investigated for use as a vaccine. The MDCK-derived H9N2 vaccine was able to induce high titers of neutralizing antibodies in chickens of different ages. Histopathological examination, direct immunofluorescence, HI assay, CD4(+)/CD8(+) ratio test, and cytokine evaluation indicated that the MDCK-derived H9N2 vaccine evoked a rapid and effective immune response to protect chickens from influenza infection. High titers of H9N2-specific antibodies were maintained in chickens for 5 months, and the MDCK-derived H9N2 vaccine had no effects on chicken growth. The use of MDCK cells in bioreactors for LPAIV vaccine production is an attractive option to prevent outbreaks of LPAIV in poultry.
Amour, Sélilah; Djhehiche, Khaled; Zamora, Adeline; Bergeret, Alain; Vanhems, Philippe
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.
Amour, Sélilah; Djhehiche, Khaled; Zamora, Adeline; Bergeret, Alain; Vanhems, Philippe
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
Background In Spain, the influenza vaccine effectiveness (VE) was estimated in the last three seasons using the observational study cycEVA conducted in the frame of the existing Spanish Influenza Sentinel Surveillance System. The objective of the study was to estimate influenza vaccine effectiveness (VE) against medically attended, laboratory-confirmed influenza-like illness (ILI) among the target groups for vaccination in Spain in the 2011–2012 season. We also studied influenza VE in the early (weeks 52/2011-7/2012) and late (weeks 8-14/2012) phases of the epidemic and according to time since vaccination. Methods Medically attended patients with ILI were systematically swabbed to collect information on exposure, laboratory outcome and confounding factors. Patients belonging to target groups for vaccination and who were swabbed <8 days after symptom onset were included. Cases tested positive for influenza and controls tested negative for any influenza virus. To examine the effect of a late season, analyses were performed according to the phase of the season and according to the time between vaccination and symptoms onset. Results The overall adjusted influenza VE against A(H3N2) was 45% (95% CI, 0–69). The estimated influenza VE was 52% (95% CI, -3 to 78), 40% (95% CI, -40 to 74) and 22% (95% CI, -135 to 74) at 3.5 months, 3.5-4 months, and >4 months, respectively, since vaccination. A decrease in VE with time since vaccination was only observed in individuals aged ≥ 65 years. Regarding the phase of the season, decreasing point estimates were only observed in the early phase, whereas very low or null estimates were obtained in the late phase for the shortest time interval. Conclusions The 2011–2012 influenza vaccine showed a low-to-moderate protective effect against medically attended, laboratory-confirmed influenza in the target groups for vaccination, in a late season and with a limited match between the vaccine and circulating strains. The
Jürgenssen, O; Moritz, A; Liehl, E; Bachmayer, H
A new influenza subunit vaccine which contains only hemagglutinin and neuraminidase antigens was investigated for reactogenicity and immunogenicity in children aged between three and 15 years. Children under six years of age received either 500 IU or 1000 IU of the commercial vaccine, those aged from six to 15 years either 1000 IU or 2000 IU. The vaccines contained the virus strains recommended by the World Health Organisation for the vaccination season 1976/77. In a double blind study the vaccinees were allocated at random to the different dosage groups. The children were examined for reactions by the vaccinating physician 24 hours after vaccination. Serum hemagglutination inhibiting antibody titers were determined before vaccination and four weeks after vaccination. In the younger age-group additional antibody determination was made two weeks after a booster injection. A very low rate of side-reactions was observed in all dosage groups. The increase of the antigen content was not associated with a higher rate of side reactions. After the first vaccination a significant rise of antibody titers could be observed in all children. After the booster injection a further increase of these antibody titers was observed. The response of the younger age group to the dosages 500 and 100 IU did not different significantly. In contrast, in the older age group the increase of the dosage from 1000 to 2000 IU was connected with a better immune response. This was especially marked in the antibody titers against the influenza B-strain virus.
Zielonka, T M; Szymańczak, M; Jakubiak, J; Nitsch-Osuch, A; Życińska, K
Despite intensive recommendations, influenza vaccination rate in medical staff in Poland ranges from about 20 % in physicians to 10 % in nurses. The objective of this work was to assess the influence of hospital influenza vaccination campaign directed toward health care workers, combined with dispensing free of charge vaccine, on vaccination rate. The campaign was conducted by the Hospital Infection Control Team of the Czerniakowski Hospital in Warsaw, Poland, separately for physicians, nurses, and physiotherapists. Overall, 37 % of medical staff were vaccinated, including 55 % of physicians and 21 % of nurses. Concerning physicians, the greatest vaccination rate was in the orthopedic (80 %) and ophthalmology units (73 %), whereas the lowest rate was in the intensive care (22 %) and neurology units (20 %). Concerning nurses, the greatest vaccination rate was in those working in the outpatient (40 %) and emergency units (29 %), whereas the lowest rate was in the ophthalmology (6 %) and surgery units (11 %). We conclude that the professional knowledge campaign combined with the incentive of free of charge vaccine substantially raises the vaccination rate among medical staff.
The history of the 1957/58 Asian flu in Germany is systematically presented for the first time. The focus is on flu vaccination, which is discussed as a yardstick of the perception of the pandemic. International expertise on influenza virology was predominantly based in Anglo-Saxon countries. German microbiologists issued no clear recommendation for preventative vaccination until 1960. Instead, quinine was relied upon as the traditional medicinal prophylaxis. Antibiotics were more frequently administered. In East Germany, little fuss was made over the Asian flu. In line with the authorities' social hygiene orientation, vaccination was accepted as a matter of principle. In the Federal Republic and West Berlin, the population rejected the vaccination largely. It was seen as a scandal that many employees were on sick leave because of the flu, thus adversely affecting the economy.
Simpson, Jacqueline K; Patalay, Rakesh; Francis, Nicholas; Roberts, Nerys
Wells syndrome is a rare disorder of unknown etiology. Precipitants include insect bites, infections, medications, malignancies, and vaccinations. Possible mechanisms include hypersensitivity reactions to antigens. There are four reports in the literature of Wells syndrome precipitated by vaccinations (hepatitis B vaccine, tetanus vaccine, tetanus-diptheria vaccine and triple antigen vaccine). We present a further case of Wells syndrome in a 22-month-old child after influenza vaccine as a novel trigger not previously reported.
Wood, J M; Newman, R W; Daas, A; Terao, E; Buchheit, K-H
The Quality of Medicines & HealthCare (EDQM, Council of Europe) and the European Union (EU) Commission to evaluate the reproducibility of clinical serology results for seasonal influenza vaccines and to assess the impact of technical differences between laboratories on the compliance with the Committee for Human Medicinal Products (CHMP) criteria set by the European Medicines Agency (EMA). The study was run in 2 phases. The present article reports the 1st phase of the study, which aimed at evaluating the variability of the results obtained by 11 laboratories (5 national control laboratories and 6 influenza vaccine manufacturers) using their routine haemagglutination inhibition (HI) assay to test a common panel of clinical trial sera. The results confirmed the limited inter-laboratory reproducibility of the HI testing of influenza vaccine clinical trial samples. In some cases a good agreement was found between laboratories, while a systematic bias or a random scatter of results was observed in other cases. Analysis of estimated systematic bias confirmed that differences between laboratories can be significant (up to 16-fold) in some cases. Correction for this bias resulted in limited improvement. Differences between laboratories were found to result in discrepant decisions on marketing acceptance of vaccines or to decisions based on compliance to different criteria. The study showed that the seroconversion (SC) and mean fold increase (MFI) criteria are more robust against systematic over- or under-estimation of titres whereas the protection rate (PR) is very sensitive to this effect. The fundamental issues with the PR criteria are discussed.
Brogan, Anita J.; Talbird, Sandra E.; Davis, Ashley E.; Thommes, Edward W.; Meier, Genevieve
ABSTRACT Trivalent inactivated influenza vaccines (IIV3s) protect against 2 A strains and one B lineage; quadrivalent versions (IIV4s) protect against an additional B lineage. The objective was to assess projected health and economic outcomes associated with IIV4 versus IIV3 for preventing seasonal influenza in the US. A cost-effectiveness model was developed to interact with a dynamic transmission model. The transmission model tracked vaccination, influenza cases, infection-spreading interactions, and recovery over 10 y (2012–2022). The cost-effectiveness model estimated influenza-related complications, direct and indirect costs (2013–2014 US$), health outcomes, and cost-effectiveness. Inputs were taken from published/public sources or estimated using regression or calibration. Outcomes were discounted at 3% per year. Scenario analyses tested the reliability of the results. Seasonal vaccination with IIV4 versus IIV3 is predicted to reduce annual influenza cases by 1,973,849 (discounted; 2,325,644 undiscounted), resulting in 12–13% fewer cases and influenza-related complications and deaths. These reductions are predicted to translate into 18,485 more quality-adjusted life years (QALYs) accrued annually for IIV4 versus IIV3. Increased vaccine-related costs ($599 million; 5.7%) are predicted to be more than offset by reduced influenza treatment costs ($699 million; 12.2%), resulting in direct medical cost saving annually ($100 million; 0.6%). Including indirect costs, savings with IIV4 are predicted to be $7.1 billion (5.6%). Scenario analyses predict IIV4 to be cost-saving in all scenarios tested apart from low infectivity, where IIV4 is predicted to be cost-effective. In summary, seasonal influenza vaccination in the US with IIV4 versus IIV3 is predicted to improve health outcomes and reduce costs. PMID:27780425
Laskowski, M.; Xiao, Y.; Charland, N.; Moghadas, S. M.
Ongoing research and technology developments hold the promise of rapid production and large-scale deployment of strain-specific or cross-protective vaccines for novel influenza viruses. We sought to investigate the impact of early vaccination on age-specific attack rates and evaluate the outcomes of different vaccination strategies that are influenced by the level of single or two-dose vaccine-induced protections. We developed and parameterized an agent-based model for two population demographics of urban and remote areas in Canada. Our results demonstrate that there is a time period before and after the onset of epidemic, during which the outcomes of vaccination strategies may differ significantly and are highly influenced by demographic characteristics. For the urban population, attack rates were lowest for children younger than 5 years of age in all vaccination strategies. However, for the remote population, the lowest attack rates were obtained for adults older than 50 years of age in most strategies. We found that the reduction of attack rates following the start of vaccination campaigns during the epidemic depends critically on the disease transmissibility, suggesting that for a sufficiently high transmissibility, vaccine delivery after the onset of epidemic has little or no effect, regardless of the population demographics. PMID:26658016
The neuraminidase protein of influenza viruses is a surface glycoprotein that has enzymatic activity to remove sialic acid, the viral receptor, from both viral and host proteins. The removal of sialic acid from viral proteins plays a key role in the release of the virus from the cell by preventing ...
Cargnelutti, Diego Esteban; Sánchez, María Victoria; Mattion, Nora Marta; Scodeller, Eduardo Alberto
In pursuit of better influenza vaccines, many strategies are being studied worldwide. An attractive alternative is the generation of a broadly cross-reactive vaccine based on the induction of cytotoxic T-lymphocytes (CTL) directed against conserved internal antigens of influenza A virus. The feasibility of this approach using recombinant viral vectors has recently been demonstrated in mice and humans by several research groups. However, similar results might also be achieved through immunization with viral proteins expressed in a prokaryotic system formulated with the appropriate adjuvants and delivery systems. This approach would be much simpler and less expensive. Recent results from several laboratories seem to confirm this is as a valid option to be considered. PMID:23337287
Fitzgerald, Thomas J.; Kang, Yoonjae; Bridges, Carolyn B.; Talbert, Todd; Vagi, Sara J.; Lamont, Brock; Graitcer, Samuel B.
Background During an influenza pandemic, to achieve early and rapid vaccination coverage and maximize the benefit of an immunization campaign, partnerships between public health agencies and vaccine providers are essential. Immunizing pharmacists represent an important group for expanding access to pandemic vaccination. However, little is known about nationwide coordination between public health programs and pharmacies for pandemic vaccine response planning. Methods To assess relationships and planning activities between public health programs and pharmacies, we analyzed data from Centers for Disease Control and Prevention assessments of jurisdictions that received immunization and emergency preparedness funding from 2012 to 2015. Results Forty-seven (88.7%) of 53 jurisdictions reported including pharmacies in pandemic vaccine distribution plans, 24 (45.3%) had processes to recruit pharmacists to vaccinate, and 16 (30.8%) of 52 established formal relationships with pharmacies. Most jurisdictions plan to allocate less than 10% of pandemic vaccine supply to pharmacies. Discussion While most jurisdictions plan to include pharmacies as pandemic vaccine providers, work is needed to establish formalized agreements between public health departments and pharmacies to improve pandemic preparedness coordination and ensure that vaccinating pharmacists are fully utilized during a pandemic. PMID:27686834
Gnatiuc, L; Buist, A S; Kato, B; Janson, C; Ait-Khaled, N; Nielsen, R; Koul, P A; Nizankowska-Mogilnicka, E; Obaseki, D; Idolor, L F; Harrabi, I; Burney, P G J
Background Increasing access to essential respiratory medicines and influenza vaccination has been a priority for over three decades. Their use remains low in low and middle income countries (LMICs) where little is known about factors influencing use, or about the use of influenza vaccination for preventing respiratory exacerbations. Methods We estimated rates of regular use of bronchodilators, inhaled corticosteroids and influenza vaccine, and predictors for use among 19,000 adults from 23 high (HIC) and LMIC sites. Findings Bronchodilators, inhaled corticosteroids and influenza vaccine were used significantly more in HIC than in LMICs after adjusting for similar clinical needs. Although used more commonly by people with symptomatic or severe respiratory disease, the gap between HIC and LMICs is not explained by prevalence of COPD or doctor-diagnosed asthma. Site-specific factors are likely to influence use differently. The gross national income per capita for the country is a strong predictor for use of these treatments, suggesting that economics influence under-treatment. Conclusion A better understanding of determinants for low use of essential respiratory medicines and influenza vaccine in low income settings remains important. Identifying and addressing these more systematically could improve access and use of effective treatments. PMID:25519786
Furman, David; Jojic, Vladimir; Sharma, Shalini; Shen-Orr, Shai; Angel, Cesar J Lopez; Onengut-Gumuscu, Suna; Kidd, Brian; Maecker, Holden T; Concannon, Patrick; Dekker, Cornelia L; Thomas, Paul G; Davis, Mark M
Cytomegalovirus (CMV) is a beta-herpes virus present in a latent form in most people worldwide. In immunosuppressed individuals, CMV can reactivate and cause serious clinical complications, but the effect of the latent state on healthy people remains elusive. We undertook a systems approach to understand the differences between seropositive and negative subjects and measured hundreds of immune system components from blood samples including cytokines and chemokines, immune cell phenotyping, gene expression, ex vivo cell responses to cytokine stimuli and the antibody response to seasonal influenza vaccination. As expected, we found decreased responses to vaccination and an overall down-regulation of immune components in aged individuals regardless of CMV serostatus. In contrast, CMV-infected young adults exhibited an overall up-regulation of immune components including enhanced antibody responses to influenza vaccination, increased CD8+ T cell sensitivity, and elevated levels of circulating IFN-γ compared to uninfected individuals. Experiments with young mice infected with murine CMV also showed significant protection from an influenza virus challenge compared with uninfected animals, although this effect declined with time. These data show that CMV and its murine equivalent can have a beneficial effect on the immune response of young, healthy individuals, which may explain the continued coexistence of CMV and mammals throughout their evolution. PMID:25834109
Jiang, Jiu; Fisher, Erin M; Concannon, Mark; Lustigman, Sara; Shen, Hao; Murasko, Donna M
Immunization is the best way to prevent seasonal epidemics and pandemics of influenza. There are two kinds of influenza vaccines available in the United States: an inactivated vaccine (TIV) and an attenuated vaccine; however, only TIV is approved for immunization of the elderly population. While the aged population has the highest rate of influenza vaccination, the protective efficacy is low as evidenced by elderly individuals having the highest mortality associated with influenza. Recently, we reported that an adjuvant derived from the helminth parasite Onchocerca volvulus, named O. volvulus activation-associated secreted protein-1 (Ov-ASP-1), can significantly enhance the protective efficacy of an inactivated vaccine (TIV) in young adult mice. In the current study, we examined whether this recombinant Ov-ASP-1 (rOv-ASP-1) can enhance the efficacy of TIV in aged mice as well. While primary immunization with TIV alone produced only a low level of influenza-specific antibodies (total IgG, IgG1, and IgG2c) in aged mice, the antibody levels were significantly increased after immunization with TIV+rOv-ASP-1. More importantly, the level of the total IgG in aged mice administered TIV+rOv-ASP-1 was comparable to that of young adult mice immunized with TIV alone. Co-administration of rOv-ASP-1 induced a low level of cross-reactive antibody and enhanced the protective efficacy of TIV in aged mice, reflected by significantly increased survival after challenge with a heterologous influenza virus. rOv-ASP-1 was also superior to the conventional adjuvant alum in inducing specific IgG after TIV immunization in aged mice, and in conferring protection after challenge. These results demonstrate that rOv-ASP-1 may serve as a potential adjuvant for influenza vaccine to improve the efficacy of protection in the elderly.
Szyszko, E; Brokstad, K; Cox, R J; Hovden, A-O; Madhun, A; Haaheim, L R
Vaccination provides the most effective method of limiting the impact of influenza. Inactivated influenza vaccines are available in three formulations and more information needs to be generated on how antigen presented in different vaccine formulations influences the subsequent immune response. In the present study, we have investigated the effect of two different influenza vaccine formulations on the resulting antibody and cytokine responses and compared these responses with influenza infection. Mice were vaccinated intramuscularly with one or two doses of whole or split virus vaccine or alternatively intranasally infected with influenza virus. Lymphocytes were isolated from spleen cells and stimulated in vitro for 24 or 72 h for analysis of cytokine profile at the gene expression and at the protein level. Additionally, whole blood was collected and the serum antibody response investigated by haemagglutination inhibition (HI) and enzyme-linked immunosorbent assay (ELISA). We found that one dose of whole virus vaccine induced higher antibody and cytokine responses and thus was more immunogenic in unprimed mice than split virus vaccine. Whole virus vaccine induced a strong IFN-gamma (type 1) immune response after one dose of vaccine and a more mixed cytokine response after the second dose. Split virus vaccine induced a type 2 response, particularly after two vaccine doses. Our results show that two doses of vaccine (both vaccine formulation) were more effective in induction of Th2 type of cytokines and thus indicate that both the formulation and also the number of vaccine doses substantially influences the magnitude and quality of the immune response.
Edwards, Kate M; Burns, Victoria E; Allen, Louise M; McPhee, Jamie S; Bosch, Jos A; Carroll, Douglas; Drayson, Mark; Ring, Christopher
The immune response to vaccination in animals can be enhanced by exposure to acute stress at the time of vaccination. The efficacy of this adjuvant strategy for vaccination in humans requires investigation. The current study employed a randomised controlled trial design to examine the effects of eccentric exercise prior to influenza vaccination on the antibody and cell-mediated responses. Sixty young healthy adults (29 men, 31 women) performed eccentric contractions of the deltoid and biceps brachii muscles of the non-dominant arm (exercise group) or rested quietly (control group), and were vaccinated 6h later in the non-dominant arm. Change in arm circumference and pain were measured to assess the physiological response to exercise. Antibody titres were measured pre-vaccination and at 6- and 20-week follow-ups. Interferon-gamma in response to in vitro stimulation by the whole vaccine, an index of the cell-mediated response, was measured 8 weeks post-vaccination. Interferon-gamma responses were enhanced by exercise in men, whereas antibody titres were enhanced by eccentric exercise in women but not in men. Men showed greater increase in arm circumference after eccentric exercise than women but there was no difference in reported pain. The interferon-gamma response was positively associated with the percentage increase in arm circumference among the exercise group. Eccentric exercise exerted differential effects on the response to vaccination in men and women, with enhancement of the antibody response in women, but enhancement of the cell-mediated response in men. Eccentric exercise of the muscle at the site of vaccine administration should be explored further as a possible behavioural adjuvant to vaccination.
The interruption to the New Zealand influenza vaccine supply in 2005 (caused by a manufacturing error) greatly disrupted the annual influenza vaccination programme. The sole-tendering process used by PHARMAC was blamed by some for the crisis, which may have been alleviated by having more than one supplier. In this article, the author discusses the issues resulting from having limited options of vaccine supply. Supply problems are not limited to influenza vaccine but the tight timelines required for vaccine delivery may make it wise to secure two suppliers in future. Like all health insurance, the cost of supply redundancy will be appreciable.
Influenza A virus (IAV) remains a significant global health issue causing annual epidemics, pandemics, and sporadic human infections with highly pathogenic avian or swine influenza viruses. Current inactivated and live vaccines are the mainstay of the public health response to influenza, although vaccine efficacy is lower against antigenically distinct viral strains. The first pandemic of the twenty-first century underlined the urgent need to develop new vaccines capable of protecting against a broad range of influenza strains. Such “universal” influenza vaccines are based on the idea of heterosubtypic immunity, wherein immune responses to epitopes conserved across IAV strains can confer protection against subsequent infection and disease. T-cells recognizing conserved antigens are a key contributor in reducing viral load and limiting disease severity during heterosubtypic infection in animal models. Recent studies undertaken during the 2009 H1N1 pandemic provided key insights into the role of cross-reactive T-cells in mediating heterosubtypic protection in humans. This review focuses on human influenza to discuss the epidemiological observations that underpin cross-protective immunity, the role of T-cells as key players in mediating heterosubtypic immunity including recent data from natural history cohort studies and the ongoing clinical development of T-cell-inducing universal influenza vaccines. The challenges and knowledge gaps for developing vaccines to generate long-lived protective T-cell responses is discussed. PMID:27242800
In 2010, the Advisory Committee on Immunization Practices (ACIP) first recommended annual influenza vaccination for all persons aged ≥6 months in the United States (1). Annual influenza vaccination of all persons aged ≥6 months continues to be recommended. This document 1) describes influenza vaccine virus strains included in the U.S. seasonal influenza vaccine for 2012-13; 2) provides guidance for the use of influenza vaccines during the 2012-13 season, including an updated vaccination schedule for children aged 6 months through 8 years and a description of available vaccine products and indications; 3) discusses febrile seizures associated with administration of influenza and 13-valent pneumococcal conjugate (PCV-13) vaccines; 4) provides vaccination recommendations for persons with a history of egg allergy; and 5) discusses the development of quadrivalent influenza vaccines for use in future influenza seasons. Information regarding issues related to influenza vaccination that are not addressed in this update is available in CDC's Prevention and Control of Influenza with Vaccines: Recommendations of the Advisory Committee on Immunization Practices (ACIP), 2010 and associated updates (1,2).
Avian influenza (AI) vaccines have emerged to be a viable emergency tool for use in a comprehensive strategy for dealing with high pathogenicity (HP) AI in developed countries. However, the available doses of inactivated AI vaccine are limited to national vaccine banks and inventory stocks of some ...
Buchan, Sarah A.; Rosella, Laura C.; Finkelstein, Michael; Juurlink, David; Isenor, Jennifer; Marra, Fawziah; Patel, Anik; Russell, Margaret L.; Quach, Susan; Waite, Nancy; Kwong, Jeffrey C.
BACKGROUND: Uptake of influenza vaccination in Canada remains suboptimal despite widespread public funding. To increase access, several provinces have implemented policies permitting pharmacists to administer influenza vaccines in community pharmacies. We examined the impact of such policies on the uptake of seasonal influenza vaccination in Canada. METHODS: We pooled data from the 2007–2014 cycles of the Canadian Community Health Survey (n = 481 526). To determine the impact of influenza vaccine administration by pharmacists, we estimated the prevalence ratio for the association between the presence of a pharmacist policy and individual-level vaccine uptake using a modified Poisson regression model (dependent variable: vaccine uptake) with normalized weights while controlling for numerous health and sociodemographic factors. RESULTS: Across all survey cycles combined, 28.8% of respondents reported receiving a seasonal influenza vaccine during the 12 months before survey participation. Introduction of a policy for pharmacist administration of influenza vaccine was associated with a modest increase in coverage (2.2%) and an individual’s likelihood of uptake (adjusted prevalence ratio 1.05, 95% confidence interval 1.02–1.08). INTERPRETATION: Uptake of influenza immunization was modestly increased in Canadian jurisdictions that allowed pharmacists to administer influenza vaccines. PMID:27503864
Mallajosyula, Jyothi K; Hiatt, Ernie; Hume, Steve; Johnson, Ashley; Jeevan, Trushar; Chikwamba, Rachel; Pogue, Gregory P; Bratcher, Barry; Haydon, Hugh; Webby, Richard J; McCormick, Alison A
Recombinant subunit vaccines are an efficient strategy to meet the demands of a possible influenza pandemic, because of rapid and scalable production. However, vaccines made from recombinant hemagglutinin (HA) subunit protein are often of low potency, requiring high dose or boosting to generate a sustained immune response. We have improved the immunogenicity of a plant-made HA vaccine by chemical conjugation to the surface of the Tobacco mosaic virus (TMV) which is non infectious in mammals. We have previously shown that TMV is taken up by mammalian dendritic cells and is a highly effective antigen carrier. In this work, we tested several TMV-HA conjugation chemistries, and compared immunogenicity in mice as measured by anti-HA IgG titers and hemagglutination inhibition (HAI). Importantly, pre-existing immunity to TMV did not reduce initial or boosted titers. Further optimization included dosing with and without alum or oil-in water adjuvants. Surprisingly, we were able to stimulate potent immunogenicity and HAI titers with a single 15µg dose of HA as a TMV conjugate. We then evaluated the efficacy of the TMV-HA vaccine in a lethal virus challenge in mice. Our results show that a single dose of the TMV-HA conjugate vaccine is sufficient to generate 50% survival, or 100% survival with adjuvant, compared with 10% survival after vaccination with a commercially available H1N1 vaccine. TMV-HA is an effective dose-sparing influenza vaccine, using a single-step process to rapidly generate large quantities of highly effective flu vaccine from an otherwise low potency HA subunit protein. PMID:24378714
Mallajosyula, Jyothi K; Hiatt, Ernie; Hume, Steve; Johnson, Ashley; Jeevan, Trushar; Chikwamba, Rachel; Pogue, Gregory P; Bratcher, Barry; Haydon, Hugh; Webby, Richard J; McCormick, Alison A
Recombinant subunit vaccines are an efficient strategy to meet the demands of a possible influenza pandemic, because of rapid and scalable production. However, vaccines made from recombinant hemagglutinin (HA) subunit protein are often of low potency, requiring high dose or boosting to generate a sustained immune response. We have improved the immunogenicity of a plant-made HA vaccine by chemical conjugation to the surface of the Tobacco mosaic virus (TMV) which is non infectious in mammals. We have previously shown that TMV is taken up by mammalian dendritic cells and is a highly effective antigen carrier. In this work, we tested several TMV-HA conjugation chemistries, and compared immunogenicity in mice as measured by anti-HA IgG titers and hemagglutination inhibition (HAI). Importantly, pre-existing immunity to TMV did not reduce initial or boosted titers. Further optimization included dosing with and without alum or oil-in water adjuvants. Surprisingly, we were able to stimulate potent immunogenicity and HAI titers with a single 15 µg dose of HA as a TMV conjugate. We then evaluated the efficacy of the TMV-HA vaccine in a lethal virus challenge in mice. Our results show that a single dose of the TMV-HA conjugate vaccine is sufficient to generate 50% survival, or 100% survival with adjuvant, compared with 10% survival after vaccination with a commercially available H1N1 vaccine. TMV-HA is an effective dose-sparing influenza vaccine, using a single-step process to rapidly generate large quantities of highly effective flu vaccine from an otherwise low potency HA subunit protein.
Blyth, Christopher C; Macartney, Kristine K; Hewagama, Saliya; Senenayake, Sanjaya; Friedman, N Deborah; Simpson, Graham; Upham, John; Kotsimbos, Tom; Kelly, Paul; Cheng, Allen C
The Influenza Complications Alert Network (FluCAN) is a sentinel hospital-based surveillance programme operating in all states and territories in Australia. We summarise the epidemiology of children hospitalised with laboratory-confirmed influenza in 2014 and reports on the effectiveness of inactivated trivalent inactivated vaccine (TIV) in children. In this observational study, cases were defined as children admitted with acute respiratory illness (ARI) with influenza confirmed by PCR. Controls were hospitalised children with ARI testing negative for influenza. Vaccine effectiveness (VE) was estimated as 1 minus the odds ratio of vaccination in influenza positive cases compared with test-negative controls using conditional logistic regression models. From April until October 2014, 402 children were admitted with PCR-confirmed influenza. Of these, 28% were aged < 1 year, 16% were Indigenous, and 39% had underlying conditions predisposing to severe influenza. Influenza A was detected in 90% of cases of influenza; influenza A(H1N1)pdm09 was the most frequent subtype (109/141 of subtyped cases) followed by A(H3N2) (32/141). Only 15% of children with influenza received antiviral therapy. The adjusted VE of one or more doses of TIV for preventing hospitalised influenza was estimated at 55.5% (95% confidence intervals (CI): 11.6-77.6%). Effectiveness against influenza A(H1N1)pdm09 was high (91.6% , 95% CI: 36.0-98.9%) yet appeared poor against H3N2. In summary, the 2014 southern hemisphere TIV was moderately effective against severe influenza in children. Significant VE was observed against influenza A(H1N1)pdm09.
Lum, Lucy Chai See; Borja-Tabora, Charissa Fay; Breiman, Robert F; Vesikari, Timo; Sablan, Benjamin P; Chay, Oh Moh; Tantracheewathorn, Taweewong; Schmitt, Heinz-Josef; Lau, Yu-Lung; Bowonkiratikachorn, Piyaporn; Tam, John S; Lee, Bee Wah; Tan, Kah Kee; Pejcz, Jerzy; Cha, Sungho; Gutierrez-Brito, Maricruz; Kaltenis, Petras; Vertruyen, Andre; Czajka, Hanna; Bojarskas, Jurgis; Brooks, W Abdullah; Cheng, Sheau-Mei; Rappaport, Ruth; Baker, Sherryl; Gruber, William C; Forrest, Bruce D
Children aged 11 to <24 months received 2 intranasal doses of live attenuated influenza vaccine (LAIV) or placebo, 35+/-7 days apart. Dose 1 was administered concomitantly with a combined measles, mumps, and rubella vaccine (Priorix). Seroresponses to measles and mumps were similar between groups. Compared with placebo, response rates to rubella in LAIV+Priorix recipients were statistically lower at a 15 IU/mL threshold (83.9% vs 78.0%) and the prespecified noninferiority criteria were not met. In a post hoc analysis using an alternate widely accepted threshold of 10 IU/mL, the noninferiority criteria were met (93.4% vs 89.8%). Concomitant administration with Priorix did not affect the overall influenza protection rate of LAIV (78.4% and 63.8% against antigenically similar influenza strains and any strain, respectively).
Halloran, M Elizabeth; Piedra, Pedro A; Longini, Ira M; Gaglani, Manjusha J; Schmotzer, Brian; Fewlass, Charles; Herschler, Gayla B; Glezen, W Paul
In the 2003-2004 influenza season, the predominant circulating influenza A (H3N2) virus in the United States was similar antigenically to A/Fujian/411/2002 (H3N2), a drift variant of A/Panama/2007/99 (H3N2), the vaccine strain. That year, a field study of trivalent live-attenuated influenza vaccine (LAIV-T) was conducted in Temple-Belton, Texas, as part of a larger community-based, non-randomized, open-label study in three communities that began in August 1998 [Gaglani MJ, Piedra PA, Herschler GB, Griffith ME, Kozinetz CA, Riggs MW, et al. Direct effectiveness of the trivalent, cold-adapted, influenza virus vaccine (CAIV-T) against the 2000-2001 influenza A (H1N1) and B epidemic in healthy children. Arch Pediatr Adolesc Med 2004;158:65-73; Piedra PA, Gaglani MJ, Kozinetz CA, Herschler G, Riggs M, Griffith M, et al. Herd immunity in adults against influenza-related illnesses with use of the trivalent-live attenuated influenza vaccine (CAIV-T) in children. Vaccine 2005;23:1540-8; Piedra PA, Gaglani MJ, Riggs M, Herschler G, Fewlass C, Watts M, et al. Live attenuated influenza vaccine, trivalent, is safe in healthy children 18 months to 4 years, 5 to 9 years, and 10 to 18 years of age in a community-based, nonrandomized, open-label trial. Pediatrics 2005;116:397-407]. Participants were healthy children aged 5-18 years. The analysis here concerns 6403 children in the Scott & White Health Plan (SWHP) database living within zip codes of the Temple-Belton area, of whom 1706 received LAIV-T and 548 received trivalent inactivated vaccine (TIV) in 2003, 983 had been previously vaccinated in 1998-2001, but not in 2002-2003 or 2003, and 3166 had never been vaccinated. The main outcome measure was medically-attended acute respiratory illness (MAARI). Surveillance culture results were incorporated into the analysis to estimate efficacy against culture-confirmed influenza illness. Vaccine effectiveness of LAIV-T against MAARI was 26% (95% confidence interval (CI) 11, 39). Vaccine
McLean, Kenneth A; Goldin, Shoshanna; Nannei, Claudia; Sparrow, Erin; Torelli, Guido
A global shortage and inequitable access to influenza vaccines has been cause for concern for developing countries who face dire consequences in the event of a pandemic. The Global Action Plan for Influenza Vaccines (GAP) was launched in 2006 to increase global capacity for influenza vaccine production to address these concerns. It is widely recognized that well-developed infrastructure to produce seasonal influenza vaccines leads to increased capacity to produce pandemic influenza vaccines. This article summarizes the results of a survey administered to 44 manufacturers to assess their production capacity for seasonal influenza and pandemic influenza vaccine production. When the GAP was launched in 2006, global production capacity for seasonal and pandemic vaccines was estimated to be 500million and 1.5billion doses respectively. Since 2006 there has been a significant increase in capacity, with the 2013 survey estimating global capacity at 1.5billion seasonal and 6.2billion pandemic doses. Results of the current survey showed that global seasonal influenza vaccine production capacity has decreased since 2013 from 1.504billion doses to 1.467billion doses. However, notwithstanding the overall global decrease in seasonal vaccine capacity there were notable positive changes in the distribution of production capacity with increases noted in South East Asia (SEAR) and the Western Pacific (WPR) regions, albeit on a small scale. Despite a decrease in seasonal capacity, there has been a global increase of pandemic influenza vaccine production capacity from 6.2 billion doses in 2013 to 6.4 billion doses in 2015. This growth can be attributed to a shift towards more quadrivalent vaccine production and also to increased use of adjuvants. Pandemic influenza vaccine production capacity is at its highest recorded levels however challenges remain in maintaining this capacity and in ensuring access in the event of a pandemic to underserved regions.
Harris, Katherine M; Uscher-Pines, Lori; Mattke, Soeren; Kellermann, Arthur L
Vaccine-preventable disease continues to take a heavy toll on adults despite the widespread availability of effective vaccines. This article identifies where efforts to improve the delivery of adult vaccination have stalled and recommends targeted strategies that are supported by available evidence and build on existing infrastructure. The authors conducted a comprehensive review of the published literature on adult immunization, a stakeholder workshop, and follow-up interviews with meeting participants and additional experts. They also partnered with an organization represented at the workshop to conduct a telephone survey of adults to learn about the relationship between influenza vaccination and beliefs about the safety of influenza vaccine. Findings include that office-based providers remain the primary source of vaccination, though a substantial proportion of physicians who treat adults appear not to vaccinate at all and adult vaccination is infrequently discussed at health care encounters. Adult practices also lack a strong business case to offer vaccination, as it entails substantial fixed costs. In addition, achieving substantial increases in adult vaccination will require persuading large numbers of individuals disinclined to be vaccinated. Vaccination stakeholders need to engage in a collaborative fashion to promote adult vaccination and the integration of advice about vaccination into routine office-based practice. Recommendations include strengthening evidence surrounding practice gaps and the economic value of promoting vaccination in office-based settings, improving guidance to providers about vaccinating adults, and formalizing procedures for referring patients to complementary vaccinators.
Domínguez, Àngela; Soldevila, Núria; Toledo, Diana; Godoy, Pere; Castilla, Jesús; Force, Lluís; Morales, María; Mayoral, José María; Egurrola, Mikel; Tamames, Sonia; Martín, Vicente; Astray, Jenaro
Vaccination of the elderly is an important factor in limiting the impact of influenza in the community. The aim of this study was to investigate the factors associated with influenza vaccination coverage in hospitalized patients aged ≥65 years hospitalized due to causes unrelated to influenza in Spain. We carried out a cross-sectional study. Bivariate analysis was performed comparing vaccinated and unvaccinated patients, taking in to account sociodemographic variables and medical risk conditions. Multivariate analysis was performed using multilevel regression models. We included 1038 patients: 602 (58%) had received the influenza vaccine in the 2013–14 season. Three or more general practitioner visits (OR = 1.61; 95% CI 1.19–2.18); influenza vaccination in any of the 3 previous seasons (OR = 13.57; 95% CI 9.45–19.48); and 23-valent pneumococcal polysaccharide vaccination (OR = 1.97; 95% CI 1.38–2.80) were associated with receiving the influenza vaccine. Vaccination coverage of hospitalized elderly people is low in Spain and some predisposing characteristics influence vaccination coverage. Healthcare workers should take these characteristics into account and be encouraged to proactively propose influenza vaccination to all patients aged ≥65 years. PMID:26824383
Domínguez, Àngela; Soldevila, Núria; Toledo, Diana; Godoy, Pere; Castilla, Jesús; Force, Lluís; Morales, María; Mayoral, José María; Egurrola, Mikel; Tamames, Sonia; Martín, Vicente; Astray, Jenaro
Vaccination of the elderly is an important factor in limiting the impact of influenza in the community. The aim of this study was to investigate the factors associated with influenza vaccination coverage in hospitalized patients aged ≥ 65 years hospitalized due to causes unrelated to influenza in Spain. We carried out a cross-sectional study. Bivariate analysis was performed comparing vaccinated and unvaccinated patients, taking in to account sociodemographic variables and medical risk conditions. Multivariate analysis was performed using multilevel regression models. We included 1038 patients: 602 (58%) had received the influenza vaccine in the 2013-14 season. Three or more general practitioner visits (OR = 1.61; 95% CI 1.19-2.18); influenza vaccination in any of the 3 previous seasons (OR = 13.57; 95% CI 9.45-19.48); and 23-valent pneumococcal polysaccharide vaccination (OR = 1.97; 95% CI 1.38-2.80) were associated with receiving the influenza vaccine. Vaccination coverage of hospitalized elderly people is low in Spain and some predisposing characteristics influence vaccination coverage. Healthcare workers should take these characteristics into account and be encouraged to proactively propose influenza vaccination to all patients aged ≥ 65 years.
Yoo, Byung-Kwang; Szilagyi, Peter G.; Schaffer, Stanley J.; Humiston, Sharon G.; Rand, Cynthia M.; Albertin, Christina S.; Vincelli, Phyllis; Blumkin, Aaron K.; Shone, Laura P.; Coleman, Margaret S.
Context Although all children 6 months to 18 years are now recommended to receive influenza vaccine, the total direct and indirect costs for pediatric practices of delivering childhood influenza vaccination are unknown. Objective To estimate nationally-representative pediatric practices’ costs of providing influenza vaccination during the 2006–2007 season, and to simulate the costs pediatric practices might incur when implementing universal influenza vaccination for US children 6 months to 18 years. Design and Setting We surveyed a stratified, random sample of New York State pediatric practices (n=91) to obtain information from physicians and office managers about all practice resources associated with provision of influenza vaccination. We estimated vaccination costs for two practice sizes (small, large) and three geographic areas (urban, suburban, rural). We adjusted these data to obtain national estimates. Main Outcome Measure(s) Total practice cost for providing one influenza vaccine (2006 dollars) to children 6 months to 18 years. Results Among all respondents, the median total cost per vaccination was $28.62 (range $18.67 (25th percentile) to $45.28 (75th percentile)). The median component costs were: (1) clinical personnel/labor- $2.01, (2) non-clinical personnel/labor- $7.96, and (3) all other (overhead) costs- $10.43. Vaccine purchase costs averaged $8.22. Smaller practices and urban practices had higher costs than larger or suburban practices. Assuming that vaccine administration reimbursement for all Vaccine For Children program (VFC) eligible children is the current Medicaid median of $8.40, the financial loss across all US pediatric practices through delivering VFC vaccines would be $98 million if only one-third of children received influenza vaccine. Conclusion The total cost for pediatric practices to provide influenza vaccination is high, varies by practice characteristics, and exceeds average VFC reimbursement. Many pediatric practices may face
Sandbulte, Matthew R; Spickler, Anna R; Zaabel, Pamela K; Roth, James A
Influenza A virus in swine (IAV-S) is one of the most important infectious disease agents of swine in North America. In addition to the economic burden of IAV-S to the swine industry, the zoonotic potential of IAV-S sometimes leads to serious public health concerns. Adjuvanted, inactivated vaccines have been licensed in the United States for over 20 years, and there is also widespread usage of autogenous/custom IAV-S vaccines. Vaccination induces neutralizing antibodies and protection against infection with very similar strains. However, IAV-S strains are so diverse and prone to mutation that these vaccines often have disappointing efficacy in the field. This scientific review was developed to help veterinarians and others to identify the best available IAV-S vaccine for a particular infected herd. We describe key principles of IAV-S structure and replication, protective immunity, currently available vaccines, and vaccine technologies that show promise for the future. We discuss strategies to optimize the use of available IAV-S vaccines, based on information gathered from modern diagnostics and surveillance programs. Improvements in IAV-S immunization strategies, in both the short term and long term, will benefit swine health and productivity and potentially reduce risks to public health.
Sandbulte, Matthew R.; Spickler, Anna R.; Zaabel, Pamela K.; Roth, James A.
Influenza A virus in swine (IAV-S) is one of the most important infectious disease agents of swine in North America. In addition to the economic burden of IAV-S to the swine industry, the zoonotic potential of IAV-S sometimes leads to serious public health concerns. Adjuvanted, inactivated vaccines have been licensed in the United States for over 20 years, and there is also widespread usage of autogenous/custom IAV-S vaccines. Vaccination induces neutralizing antibodies and protection against infection with very similar strains. However, IAV-S strains are so diverse and prone to mutation that these vaccines often have disappointing efficacy in the field. This scientific review was developed to help veterinarians and others to identify the best available IAV-S vaccine for a particular infected herd. We describe key principles of IAV-S structure and replication, protective immunity, currently available vaccines, and vaccine technologies that show promise for the future. We discuss strategies to optimize the use of available IAV-S vaccines, based on information gathered from modern diagnostics and surveillance programs. Improvements in IAV-S immunization strategies, in both the short term and long term, will benefit swine health and productivity and potentially reduce risks to public health. PMID:26344946
Cummins, Nathan W.; Weaver, Eric A.; May, Shannon M.; Croatt, Anthony J.; Foreman, Oded; Kennedy, Richard B.; Poland, Gregory A.; Barry, Michael A.; Nath, Karl A.; Badley, Andrew D.
Underlying mechanisms of individual variation in severity of influenza infection and response to vaccination are poorly understood. We investigated the effect of reduced heme oxygenase-1 (HO-1) expression on vaccine response and outcome of influenza infection. HO-1-deficient and wild-type (WT) mice (kingdom, Animalia; phylum, Chordata; genus/species, Mus musculus) were infected with influenza virus A/PR/8/34 with or without prior vaccination with an adenoviral-based influenza vaccine. A genome-wide association study evaluated the expression of single-nucleotide polymorphisms (SNPs) in the HO-1 gene and the response to influenza vaccination in healthy humans. HO-1-deficient mice had decreased survival after influenza infection compared to WT mice (median survival 5.5 vs. 6.5 d, P=0.016). HO-1-deficient mice had impaired production of antibody following influenza vaccination compared to WT mice (mean antibody titer 869 vs. 1698, P=0.02). One SNP in HO-1 and one SNP in the constitutively expressed isoform HO-2 were independently associated with decreased antibody production after influenza vaccination in healthy human volunteers (P=0.017 and 0.014, respectively). HO-1 deficient mice were paired with sex- and age-matched WT controls. HO-1 affects the immune response to both influenza infection and vaccination, suggesting that therapeutic induction of HO-1 expression may represent a novel adjuvant to enhance influenza vaccine effectiveness.—Cummins, N. W., Weaver, E. A., May, S. M., Croatt, A. J., Foreman, O., Kennedy, R. B., Poland, G. A., Barry, M. A., Nath, K. A., Badley, A. D. Heme oxygenase-1 regulates the immune response to influenza virus infection and vaccination in aged mice. PMID:22490782
Suzuki, Tsubasa; Ono, Yasuhiko; Maeda, Hidenori; Tsujimoto, Yoshiki; Shobugawa, Yugo; Dapat, Clyde; Hassan, Mohd Rohaizat; Yokota, Chihiro; Kondo, Hiroki; Dapat, Isolde C; Saito, Kousuke; Saito, Reiko
Influenza vaccination is considered the single most important medical intervention for the prevention of influenza. The dose of trivalent influenza vaccine in children was increased almost double since 2011/12 season in Japan. We estimated the influenza vaccine effectiveness for children 1-11 years of age using rapid test kits in Isahaya City, involving 28,884 children-years, over two consecutive influenza seasons (2011/12 and 2012/13). Children were divided into two groups, vaccinated and unvaccinated, according to their vaccination record, which was obtained from an influenza registration program organized by the Isahaya Medical Association for all pediatric facilities in the city. There were 14,562 and 14,282 children aged from 1-11 years in the city in 2011 and 2012 respectively. In the 2011/12 season, the overall vaccine effectiveness in children from 1-11 years of age, against influenza A and B were 23% [95% confidence interval (CI): 14%-31%] and 20% [95% CI: 8%-31%], respectively. In the 2012/13 season, vaccine effectiveness against influenza A and B was 13% (95% CI: 4%-20%) and 9% (95% CI: -4%-21%), respectively. The vaccine effectiveness was estimated using the rapid diagnosis test kits. Age-stratified estimation showed that vaccine effectiveness was superior in younger children over both seasons and for both virus types. In conclusion, the trivalent influenza vaccine has a significant protective effect for children 1-11 years of age against influenza A and B infection in the 2011/12 season and against influenza A infection in the 2012/13 season in a community in Japan.
Herbert, Andrew S; Heffron, Lynn; Sundick, Roy; Roberts, Paul C
Background Influenza epidemics continue to cause morbidity and mortality within the human population despite widespread vaccination efforts. This, along with the ominous threat of an avian influenza pandemic (H5N1), demonstrates the need for a much improved, more sophisticated influenza vaccine. We have developed an in vitro model system for producing a membrane-bound Cytokine-bearing Influenza Vaccine (CYT-IVAC). Numerous cytokines are involved in directing both innate and adaptive immunity and it is our goal to utilize the properties of individual cytokines and other immunomodulatory proteins to create a more immunogenic vaccine. Results We have evaluated the immunogenicity of inactivated cytokine-bearing influenza vaccines using a mouse model of lethal influenza virus challenge. CYT-IVACs were produced by stably transfecting MDCK cell lines with mouse-derived cytokines (GM-CSF, IL-2 and IL-4) fused to the membrane-anchoring domain of the viral hemagglutinin. Influenza virus replication in these cell lines resulted in the uptake of the bioactive membrane-bound cytokines during virus budding and release. In vivo efficacy studies revealed that a single low dose of IL-2 or IL-4-bearing CYT-IVAC is superior at providing protection against lethal influenza challenge in a mouse model and provides a more balanced Th1/Th2 humoral immune response, similar to live virus infections. Conclusion We have validated the protective efficacy of CYT-IVACs in a mammalian model of influenza virus infection. This technology has broad applications in current influenza virus vaccine development and may prove particularly useful in boosting immune responses in the elderly, where current vaccines are minimally effective. PMID:19393093
Lu, Degan; Qiao, Yanru; Brown, Natalie E.; Wang, Junling
vaccine coverage between whites and the minority groups were no longer significant for adults aged 50–64 years. However, the difference were still statistically significant for those aged ≥65 years. Conclusions In the United States, there are significant disparities in influenza vaccination by race and ethnicity for adults over 65 years with at least one chronic health condition. Future research is needed to help develop more targeted interventions to address these issues and improve influenza vaccination rates. PMID:28081234
Ilyushina, Natalia A.; Haynes, Brenda C.; Hoen, Anne G.; Khalenkov, Alexey M.; Housman, Molly L.; Brown, Eric P.; Ackerman, Margaret E.; Treanor, John J.; Luke, Catherine J.; Subbarao, Kanta; Wright, Peter F.
Background. Live attenuated influenza vaccine (LAIV) and inactivated influenza vaccine (IIV) are available for children. Local and systemic immunity induced by LAIV followed a month later by LAIV and IIV followed by LAIV were investigated with virus recovery after LAIV doses as surrogates for protection against influenza on natural exposure. Methods. Fifteen children received IIV followed by LAIV, 13 an initial dose of LAIV, and 11 a second dose of LAIV. The studies were done during autumn 2009 and autumn 2010 with the same seasonal vaccine (A/California/07/09 [H1N1], A/Perth/16/09 [H3N2], B/Brisbane/60/08). Results. Twenty-eight of 39 possible influenza viral strains were recovered after the initial dose of LAIV. When LAIV followed IIV, 21 of 45 viral strains were identified. When compared to primary LAIV infection, the decreased frequency of shedding with the IIV-LAIV schedule was significant (P = .023). With LAIV-LAIV, the fewest viral strains were recovered (3/33)—numbers significantly lower (P < .001) than shedding after initial LAIV and after IIV-LAIV (P < .001). Serum hemagglutination inhibition antibody responses were more frequent after IIV than LAIV (P = .02). In contrast, more mucosal immunoglobulin A responses were seen with LAIV. Conclusions. LAIV priming induces greater inhibition of virus recovery on LAIV challenge than IIV priming. The correlate(s) of protection are the subject of ongoing analysis. Clinical Trials Registration. NCT01246999. PMID:25165161
Wang, Wenling; Li, Renqing; Deng, Yao; Lu, Ning; Chen, Hong; Meng, Xin; Wang, Wen; Wang, Xiuping; Yan, Kexia; Qi, Xiangrong; Zhang, Xiangmin; Xin, Wei; Lu, Zhenhua; Li, Xueren; Bian, Tao; Gao, Yingying; Tan, Wenjie; Ruan, Li
The conventional hemagglutinin (HA)- and neuraminidase (NA)-based influenza vaccines need to be updated most years and are ineffective if the glycoprotein HA of the vaccine strains is a mismatch with that of the epidemic strain. Universal vaccines targeting conserved viral components might provide cross-protection and thus complement and improve conventional vaccines. In this study, we generated DNA plasmids and recombinant vaccinia viruses expressing the conserved proteins nucleoprotein (NP), polymerase basic 1 (PB1), and matrix 1 (M1) from influenza virus strain A/Beijing/30/95 (H3N2). BALB/c mice were immunized intramuscularly with a single vaccine based on NP, PB1, or M1 alone or a combination vaccine based on all three antigens and were then challenged with lethal doses of the heterologous influenza virus strain A/PR/8/34 (H1N1). Vaccines based on NP, PB1, and M1 provided complete or partial protection against challenge with 1.7 50% lethal dose (LD50) of PR8 in mice. Of the three antigens, NP-based vaccines induced protection against 5 LD50 and 10 LD50 and thus exhibited the greatest protective effect. Universal influenza vaccines based on the combination of NP, PB1, and M1 induced a strong immune response and thus might be an alternative approach to addressing future influenza virus pandemics.
Schwartz, Benjamin; Orenstein, Walter A
Few catastrophes can compare with the global impact of a severe influenza pandemic. The 1918-1919 pandemic was associated with more than 500,000 deaths in the USA and an estimated 20-40 million deaths worldwide, though some place the global total much higher. In an era when infectious disease mortality had been steadily decreasing, the 1918-1919 pandemic caused a large spike in overall population mortality, temporarily reversing decades of progress. The US Department of Health and Human Services, extrapolating from the 1918-1919 pandemic to the current US population size and demographics, has estimated that a comparable pandemic today would result in almost two million deaths. Vaccination is an important component of a pandemic response. Public health measures such as reduction of close contacts with others, improved hygiene, and respiratory protection with facemasks or respirators can reduce the risk of exposure and illness (Germann et al. 2006; Ferguson et al. 2006), but would not reduce susceptibility among the population. Prophylaxis with antiviral medications also may prevent illness but depends on the availability of large antiviral drug stockpiles and also does not provide long-term immunity. By contrast, immunization with a well-matched pandemic vaccine would provide active immunity and represent the most durable pandemic response. However, given current timelines for the development of a pandemic influenza vaccine and its production capacity, vaccine is likely not to be available in sufficient quantities to protect the entire population before pandemic outbreaks occur, and thus potentially limited stocks may need to be prioritized. This chapter reviews information on influenza vaccine production capacity, describes approaches used in the USA to set priorities for vaccination in the setting of limited supply, and presents a proposed strategy for prioritization.
Amour, Sélilah; Voirin, Nicolas; Regis, Corinne; Bouscambert-Duchamp, Maude; Comte, Brigitte; Coppéré, Brigitte; Pires-Cronenberger, Silene; Lina, Bruno; Vanhems, Philippe
The aim of this study was to estimate influenza vaccine effectiveness (IVE) against laboratory-confirmed influenza among hospitalized patients. A case-control investigation was based on the prospective surveillance of influenza-like illness (ILI) during five flu seasons. We compared influenza-positive cases and influenza-negative controls. Unadjusted overall IVE was 62% (95% confidence interval 24% to 81%). We found that IVE was lower during the 2004-05 flu season (11%; 95% CI -232% to 76%) when the vaccine and circulating viruses were mismatched. Expansion of the study to other hospitals could provide IVE estimates earlier in the season, for different age groups and emerging virus strains.
Rodriguez, Laura; Nogales, Aitor; Reilly, Emma C; Topham, David J; Murcia, Pablo R; Parrish, Colin R; Martinez Sobrido, Luis
Canine influenza is a contagious respiratory disease in dogs caused by two subtypes (H3N2 and H3N8) of canine influenza virus (CIV). Currently, only inactivated influenza vaccines (IIVs) are available for the prevention of CIVs. Historically, live-attenuated influenza vaccines (LAIVs) have been shown to produce better immunogenicity and protection efficacy than IIVs. Here, we have engineered a CIV H3N2 LAIV by using the internal genes of a previously described CIV H3N8 LAIV as a master donor virus (MDV) and the surface HA and NA genes of a circulating CIV H3N2 strain. Our findings show that CIV H3N2 LAIV replicates efficiently at low temperature but its replication is impaired at higher temperatures. The CIV H3N2 LAIV was attenuated in vivo but induced better protection efficacy in mice against challenge with wild-type CIV H3N2 than a commercial CIV H3N2 IIV. This is the first description of a LAIV for the prevention of CIV H3N2 in dogs.
Rahn, J; Hoffmann, D; Harder, T C; Beer, M
Influenza A viruses are important pathogens with a very broad host spectrum including domestic poultry and swine. For preventing clinical disease and controlling the spread, vaccination is one of the most efficient tools. Classical influenza vaccines for domestic poultry and swine are conventional inactivated preparations. However, a very broad range of novel vaccine types ranging from (i) nucleic acid-based vaccines, (ii) replicon particles, (iii) subunits and virus-like particles, (iv) vectored vaccines, or (v) live-attenuated vaccines has been described, and some of them are now also used in the field. The different novel approaches for vaccines against avian and swine influenza virus infections are reviewed, and additional features like universal vaccines, novel application approaches and the "differentiating infected from vaccinated animals" (DIVA)-strategy are summarized.
Yin, Jiehui Kevin; Salkeld, Glenn; Heron, Leon; Khandaker, Gulam; Rashid, Harunor; Booy, Robert
Influenza is an acute respiratory illness that remains an important cause of excessive morbidity and mortality with substantial economic cost to the population. Influenza, being a virus that frequently mutates, is not amenable to elimination. Vaccination remains the most effective preventive measure. This review summarises the latest developments in the fields of biology and epidemiology relating to clinical and economic impacts of influenza disease, and vaccination. We suggest that future efforts should focus on developing safer, more effective, and cost-effective prophylactic vaccines for influenza.
De Groot, Anne S; Ardito, Matthew; Terry, Frances; Levitz, Lauren; Ross, Ted; Moise, Leonard; Martin, William
A new avian-origin influenza virus emerged near Shanghai in February 2013, and by the beginning of May it had caused over 130 human infections and 36 deaths. Human-to-human transmission of avian-origin H7N9 influenza A has been limited to a few family clusters, but the high mortality rate (27%) associated with human infection has raised concern about the potential for this virus to become a significant human pathogen. European, American, and Asian vaccine companies have already initiated the process of cloning H7 antigens such as hemagglutinin (HA) into standardized vaccine production vehicles. Unfortunately, previous H7 HA-containing vaccines have been poorly immunogenic. We used well-established immunoinformatics tools to analyze the H7N9 protein sequences and compare their T cell epitope content to other circulating influenza A strains as a means of estimating the immunogenic potential of the new influenza antigen. We found that the HA proteins derived from closely related human-derived H7N9 strains contain fewer T cell epitopes than other recently circulating strains of influenza, and that conservation of T cell epitopes with other strains of influenza was very limited. Here, we provide a detailed accounting of the type and location of T cell epitopes contained in H7N9 and their conservation in other H7 and circulating (A/California/07/2009, A/Victoria/361/2011, and A/Texas/50/2012) influenza A strains. Based on this analysis, avian-origin H7N9 2013 appears to be a "stealth" virus, capable of evading human cellular and humoral immune response. Should H7N9 develop pandemic potential, this analysis predicts that novel strategies for improving vaccine immunogenicity for this unique low-immunogenicity strain of avian-origin influenza will be urgently needed.
Ha, Chrysanthy; Rios, Lenoa M.; Pannaraj, Pia S.
Background: School personnel are important for communicating with parents about school vaccination programs and recognizing influenza outbreaks. This study examined knowledge, attitudes, and practices of school personnel regarding seasonal and 2009 H1N1 influenza, vaccinations, and school outbreak investigations. Methods: Data were analyzed from…
Yen, Chia-Feng; Hsu, Shang-Wei; Loh, Ching-Hui; Fang, Wen-Hui; Wu, Chia-Ling; Chu, Cordia M.; Lin, Jin-Ding
The aim of the present study was to describe the seasonal influenza vaccination rate and to examine its determinants for children and adolescents with intellectual disabilities (ID) living in the community. A cross-sectional survey was conducted to analyze the data on seasonal influenza vaccination rate among 1055 ID individuals between the ages…
Painter, Julia E.; Sales, Jessica M.; Pazol, Karen; Wingood, Gina M.; Windle, Michael; Orenstein, Walter A.; Diclemente, Ralph J.
The Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices recently expanded annual influenza vaccination recommendations to include all children 6 months through 18 years of age. Adolescent attitudes toward influenza vaccination may play a key role in reaching this newly added age group. This study examined the…
Vaccines have been used to control a variety of piscian, avian, and mammalian diseases. Commercial usage of vaccines against avian influenza (AI) began in 1979, in Minnesota to control H4 and H6 low pathogenicity avian influenza (LPAI) which was causing economically significant disease in turkey br...
Behrouzi, Ava; Vaziri, Farzam; Rahimi-Jamnani, Fatemeh; Afrough, Parviz; Rahbar, Mohammad; Satarian, Fereshteh; Siadat, Seyed Davar
Nonencapsulated, nontypeable Hemophilus influenzae (NTHi) remains an important cause of acute otitis and respiratory diseases in children and adults. NTHi bacteria are one of the major causes of respiratory tract infections, including acute otitis media, cystic fibrosis, and community-acquired pneumonia among children, especially in developing countries. The bacteria can also cause chronic diseases such as chronic bronchitis and chronic obstructive pulmonary disease in the lower respiratory tract of adults. Such bacteria express several outer membrane proteins, some of which have been studied as candidates for vaccine development. Due to the lack of effective vaccines as well as the spread and prevalence of NTHi worldwide, there is an urgent need to design and develop effective vaccine candidates against these strains. PMID:28088130
Skene, Katherine J.; Paltiel, A. David; Shim, Eunha; Galvani, Alison P.
Background There is widespread recognition that interventions targeting “superspreaders” are more effective at containing epidemics than strategies aimed at the broader population. However, little attention has been devoted to determining optimal levels of coverage for targeted vaccination strategies, given the nonlinear relationship between program scale and the costs and benefits of identifying and successfully administering vaccination to potential superspreaders. Methods We developed a framework for such an assessment derived from a transmission model of seasonal influenza parameterized to emulate typical seasonal influenza epidemics in the US. We used this framework to estimate how the marginal benefit of expanded targeted vaccination changes with the proportion of the target population already vaccinated. Results The benefit of targeting additional superspreaders varies considerably as a function of both the baseline vaccination coverage and proximity to the herd immunity threshold. The general form of the marginal benefit function starts low, particularly for severe epidemics, increases monotonically until its peak at the point of herd immunity, and then plummets rapidly. Limitations We present a simplified transmission model, primarily designed to convey qualitative insight rather than quantitative precision. With appropriate contact data, future work could address more complex population structures, such as age structure and assortative mixing patterns. Our illustrative example highlights the general economic and epidemiological findings of our method, but does not contrive to address intervention design, policy, and resource allocation issues related to practical implementation of this particular scenario. Conclusions Our approach offers a means of estimating willingness to pay for search costs associated with targeted vaccination of superspreaders, which can inform policies regarding whether a targeted intervention should be implemented and, if so
Cobbin, Joanna C. A.; Zeng, Weiguang; Jackson, David C.; Brown, Lorena E.
Current split influenza virus vaccines that induce strain-specific neutralising antibodies provide some degree of protection against influenza infection but there is a clear need to improve their effectiveness. The constant antigenic drift of influenza viruses means that vaccines are often not an exact match to the circulating strain and so levels of relevant antibodies may not be sufficiently high to afford protection. In the situation where the emergent influenza virus is completely novel, as is the case with pandemic strains, existing vaccines may provide no benefit. In this study we tested the concept of a combination vaccine consisting of sub-optimal doses of split influenza virus vaccine mixed with a cross-protective T-cell inducing lipopeptide containing the TLR2 ligand Pam2Cys. Mice immunised with combination vaccines showed superior levels of lung viral clearance after challenge compared to either split virus or lipopeptide alone, mediated through activation of enhanced humoral and/or additional cellular responses. The mechanism of action of these vaccines was dependent on the route of administration, with intranasal administration being superior to subcutaneous and intramuscular routes, potentially through the induction of memory CD8+ T cells in the lungs. This immunisation strategy not only provides a mechanism for minimising the dose of split virus antigen but also, through the induction of cross-protective CD8+ T cells, proves a breadth of immunity to provide potential benefit upon encounter with serologically diverse influenza isolates. PMID:25522323
Liu, Jing; Wu, Jianqi; Wang, Bing; Zeng, Sheng; Qi, Feifei; Lu, Changlong; Kimura, Yoshinobu; Liu, Beixing
It is well accepted that vaccination by oral administration has many advantages over injected parenteral immunization. The present study focuses on whether oral vaccination with a DNA vaccine could induce protective immunity against respiratory challenge infection. The M1 gene of influenza A virus was used to construct DNA vaccine using pcDNA 3.1(+) plasmid, a eukaryotic expression vector. The cationic liposomes were used to deliver the constructed DNA vaccine. In vitro and in vivo expression of M1 gene was observed in the cell line and in the intestine of orally vaccinated C57BL/6 mice, respectively. It became clear that this type of oral DNA vaccination was capable of inducing both humoral and cellular immune responses, together with an augmentation of IFN-γ production. In addition, oral vaccination with liposome-encapsulated DNA vaccine could protect the mice against respiratory challenge infection. These results suggest that gastrointestinal tract, a constituent member of the common mucosal immune system, is a potent candidate applicable as a DNA vaccine route against virus respiratory diseases.
McDowell, I; Newell, C; Rosser, W
Despite recommendations supporting annual influenza vaccination for people aged 65 years or older, vaccination rates remain low. Several studies have evaluated the effect of sending mailed reminders, but few have compared alternative ways of reminding patients to receive the vaccine. In a randomized trial of 939 patients aged 65 years or older in four family practices carried out between Oct. 23 and Dec. 31, 1984, we compared three ways of reminding elderly patients to receive the vaccine: personal reminder by the physician, telephone reminder by the nurse and reminder by letter. The vaccination rates for the three groups were 22.9%, 37% and 35.1% respectively. No reminder was issued to a control group, and the rate was 9.8%. Some patients could not be reached by telephone, and some did not see the physician during the specified time. Among the patients whom the nurse actually contacted, the vaccination rate was 43.5%; the rate for patients whom the doctor actually saw was 45.1%. Overall, a telephone reminder by the nurse was the most effective method, and at an hourly salary of $16 or less this method would also be the most cost-effective. The reminders used in this study were automatically generated from a computerized medical record system. The study shows how a computerized system can be used to identify patients for whom preventive procedures are due.
... more than one disease.Children over 5 years old and adults usually do not need Hib vaccine. But it may be recommended for older children or adults with asplenia or sickle cell ... for people 5 to 18 years old with HIV. Ask your doctor for details.Your ...
Moroz, Ekaterina; Albrecht, Randy A.; Aden, Brandon; Beeder, Ann Bordwine; Yuan, Jianda; García-Sastre, Adolfo; Edlin, Brian R.; Salvatore, Mirella
Background Influenza vaccination is recommended for vulnerable individuals, including active drug users, to prevent influenza complications and decrease influenza spread. Recent studies suggest that opioids negatively regulate immune responses in experimental models, but the extent to which opioid use will affect the humoral responses to influenza vaccine in humans is unknown. This information is critical in maximizing vaccination efforts. Objective To determine whether there is a difference in antibody response after influenza vaccination in heroin or methadone users compared to control subjects. Methods We studied active heroin users, subjects on methadone maintenance treatment (MMT) and subjects that did not use any drugs before and 1 and 4 weeks after vaccination with trivalent influenza vaccine (TIV). We measured hemagglutination inhibition and microneutralization titers, and we compared geometric mean titers (GMT), and rates of seroprotection and seroconversion for each of the vaccine strains among the 3 groups of subjects. Results Heroin users, subjects on MMT and non-user controls mount a similarly robust serologic response to TIV. GMT and rates of seroprotection and seroconversion were not significantly different among groups. Conclusion Our results suggest that opioid use do not significantly alter antibody responses to influenza vaccine supporting the vaccination effort in these populations. PMID:26859239
Arao, Robert F; Rosenberg, Kenneth D; McWeeney, Shannon; Hedberg, Katrina
In spite of increased risk of influenza complications during pregnancy, only half of US pregnant women get influenza vaccination. We surveyed physician prenatal care providers in Oregon to assess their knowledge and behaviors regarding vaccination of pregnant women. From September through November 2011, a state-wide survey was mailed to a simple random sample (n = 1,114) of Oregon obstetricians and family physicians. The response rate was 44.5 %. Of 496 survey respondents, 187 (37.7 %) had provided prenatal care within the last 12 months. Of these, 88.5 % reported that they routinely recommended influenza vaccine to healthy pregnant patients. No significant differences in vaccine recommendation were found by specialty, practice location, number of providers in their practice, physician gender or years in practice. In multivariable regression analysis, routinely recommending influenza vaccine was significantly associated with younger physician age [adjusted odds ratio (AOR) 2.01, 95 % confidence interval (CI) 1.29-3.13] and greater number of pregnant patients seen per week (AOR 1.95, 95 % CI 1.25-3.06). Among rural physicians, fewer obstetricians (90.3 %) than family physicians (98.5 %) had vaccine-appropriate storage units (p = 0.001). Most physician prenatal care providers understand the importance of influenza vaccination during pregnancy. To increase influenza vaccine coverage among pregnant women, it will be necessary to identify and address patient barriers to receiving influenza vaccination during pregnancy.
Wang, Lulan; Liu, Su-Yang; Chen, Hsiang-Wen; Xu, Juan; Chapon, Maxime; Zhang, Tao; Zhou, Fan; Wang, Yao E; Quanquin, Natalie; Wang, Guiqin; Tian, Xiaoli; He, Zhanlong; Liu, Longding; Yu, Wenhai; Sanchez, David Jesse; Liang, Yuying; Jiang, Taijiao; Modlin, Robert; Bloom, Barry R; Li, Qihan; Deng, Jane C; Zhou, Paul; Qin, F Xiao-Feng; Cheng, Genhong
New influenza vaccines that provide effective and broad protection are desperately needed. Live attenuated viruses are attractive vaccine candidates because they can elicit both humoral and cellular immune responses. However, recent formulations of live attenuated influenza vaccines (LAIVs) have not been protective. We combined high-coverage transposon mutagenesis of influenza virus with a rapid high-throughput screening for attenuation to generate W7-791, a live attenuated mutant virus strain. W7-791 produced only a transient asymptomatic infection in adult and neonatal mice even at doses 100-fold higher than the LD50 of the parent strain. A single administration of W7-791 conferred full protection to mice against lethal challenge with H1N1, H3N2, and H5N1 strains, and improved viral clearance in ferrets. Adoptive transfer of T cells from W7-791-immunized mice conferred heterologous protection, indicating a role for T cell-mediated immunity. These studies present an LAIV development strategy to rapidly generate and screen entire libraries of viral clones.
Jiménez-García, Rodrigo; Herńndez-Barrera, Valentín; Rodríguez-Rieiro, Cristina; de Andrés, Ana López; Miguel-Diez, Javier de; Trujillo, Isabel Jimenez; Carrasco-Garrido, Pilar
We investigated the effectiveness of applying age-based strategies to improve influenza vaccination coverage in Spain. We described and compared influenza vaccination coverage from 2003 to 2010 between those Spanish autonomous regions (AR) that lowered the age limit to 60 y and those regions that maintained the limit at 65 y. We used data collected from two surveys covering a representative sample of the Spanish population aged ≥ 16 y [Spanish National Health Survey (SNHS) 2003/2004 and the European Health Survey for Spain (EHSS) 2009/2010]. The study population (persons aged ≥ 60 y) comprised 7,496 persons in the SNHS and 7,686 in the EHSS. In 2010, those AR which had reduced the age limit had higher coverage for all age groups analyzed-regardless of the presence of associated chronic conditions-than AR which continued vaccination for those ≥ 65 y. The greatest differences appeared in individuals aged 60 to 64 y (36.9% vs. 24.4% for individuals without chronic conditions, 59.1% vs. 52.9% for those with chronic conditions, and 43.3% vs. 32.3% for the entire age group). Multivariate analysis showed that those AR which lowered the age limit increased total coverage for all age groups, specifically among individuals with chronic conditions aged 60 to 64 y (IRR 1.18; 95% CI, 1.01-1.54) and ≥ 65 y (IRR 1.07; 95% CI, 1.00-1.14). No significant changes were observed over time for the AR that continued vaccinating people aged ≥ 65 y. Our results suggest that age-based strategies are effective for improving influenza vaccination coverage in Spain.
Meliopoulos, Victoria A.; Wang, Wei; Lin, Xudong; Stucker, Karla M.; Halpin, Rebecca A.; Stockwell, Timothy B.; Schultz-Cherry, Stacey
propagating the virus under well-controlled laboratory conditions, we found that the FluMist vaccine backbone could regain virulence to cause severe disease in mice. The identification of the responsible substitutions and elucidation of the underlying mechanisms provide unique insights into the attenuation of influenza virus, which is important to basic research on vaccines, attenuation reversion, and replication. In addition, this study suggests that the safety of LAIVs should be closely monitored after mass vaccination and that novel strategies to continue to improve LAIV vaccine safety should be investigated. PMID:27440882
Yu, Wei; Yang, Fan; Yang, Jinghui; Ma, Lei; Cun, Yina; Song, Shaohui; Liao, Guoyang
Usage of influenza vaccine is the best choice measure for preventing and conclusion of influenza virus infection. Although it has been used of chicken embryo to produce influenza vaccine, following with WHO recommended vaccine strain, there were uncontrollable factors and its deficiencies, specially, during an influenza pandemic in the world. The Vero cells are used for vaccine production of a few strains including influenza virus, because of its homology with human, recommended by WHO. However, as known most of the influenza viruses strains could not culture by Vero cells. It was used two high-yield influenza viruses adapted in Vero cells as donor viruses, such as A/Yunnan/1/2005Va (H3N2) and B/Yunnan/2/2005Va (B), to construct high-yield wild influenza virus in Vero cells under antibody selection pressure. After reassortment and passages, it obtained the new Vaccine strains with A/Tianjin/15/2009Va (H1N1), A/Fujian/196/2009Va (H3N2) and B/Chongqing/1384/2010Va (B), which was not only completely keeping their original antigenic (HA and NA), but also grown well in Vero cells with high-yield. All results of gene analysis and HA, HI shown that this reassortment method could be used to find new direction to product the influenza vaccine. J. Med. Virol. 88:1914-1921, 2016. © 2016 Wiley Periodicals, Inc.
Sheikh, Qamar M.; Gatherer, Derek; Reche, Pedro A; Flower, Darren R.
Motivation: Influenza A viral heterogeneity remains a significant threat due to unpredictable antigenic drift in seasonal influenza and antigenic shifts caused by the emergence of novel subtypes. Annual review of multivalent influenza vaccines targets strains of influenza A and B likely to be predominant in future influenza seasons. This does not induce broad, cross protective immunity against emergent subtypes. Better strategies are needed to prevent future pandemics. Cross-protection can be achieved by activating CD8+ and CD4+ T cells against highly conserved regions of the influenza genome. We combine available experimental data with informatics-based immunological predictions to help design vaccines potentially able to induce cross-protective T-cells against multiple influenza subtypes. Results: To exemplify our approach we designed two epitope ensemble vaccines comprising highly conserved and experimentally verified immunogenic influenza A epitopes as putative non-seasonal influenza vaccines; one specifically targets the US population and the other is a universal vaccine. The USA-specific vaccine comprised 6 CD8+ T cell epitopes (GILGFVFTL, FMYSDFHFI, GMDPRMCSL, SVKEKDMTK, FYIQMCTEL, DTVNRTHQY) and 3 CD4+ epitopes (KGILGFVFTLTVPSE, EYIMKGVYINTALLN, ILGFVFTLTVPSERG). The universal vaccine comprised 8 CD8+ epitopes: (FMYSDFHFI, GILGFVFTL, ILRGSVAHK, FYIQMCTEL, ILKGKFQTA, YYLEKANKI, VSDGGPNLY, YSHGTGTGY) and the same 3 CD4+ epitopes. Our USA-specific vaccine has a population protection coverage (portion of the population potentially responsive to one or more component epitopes of the vaccine, PPC) of over 96 and 95% coverage of observed influenza subtypes. The universal vaccine has a PPC value of over 97 and 88% coverage of observed subtypes. Availability and Implementation: http://imed.med.ucm.es/Tools/episopt.html. Contact: email@example.com PMID:27402904
Both pandemic and seasonal influenza are receiving more attention from mass media than ever before. Topics such as epidemic severity and vaccination are changing the way in which we perceive the utility of disease prevention. Voluntary influenza vaccination has been recently modeled using inductive reasoning games. It has thus been found that severe epidemics may occur because individuals do not vaccinate and, instead, attempt to benefit from the immunity of their peers. Such epidemics could be prevented by voluntary vaccination if incentives were offered. However, a key assumption has been that individuals make vaccination decisions based on whether there was an epidemic each influenza season; no other epidemiological information is available to them. In this work, we relax this assumption and investigate the consequences of making more informed vaccination decisions while no incentives are offered. We obtain three major results. First, individuals will not cooperate enough to constantly prevent influenza epidemics through voluntary vaccination no matter how much they learned about influenza epidemiology. Second, broadcasting epidemiological information richer than whether an epidemic occurred may stabilize the vaccination coverage and suppress severe influenza epidemics. Third, the stable vaccination coverage follows the trend of the perceived benefit of vaccination. However, increasing the amount of epidemiological information released to the public may either increase or decrease the perceived benefit of vaccination. We discuss three scenarios where individuals know, in addition to whether there was an epidemic, (i) the incidence, (ii) the vaccination coverage and (iii) both the incidence and the vaccination coverage, every influenza season. We show that broadcasting both the incidence and the vaccination coverage could yield either better or worse vaccination coverage than broadcasting each piece of information on its own.
Both pandemic and seasonal influenza are receiving more attention from mass media than ever before. Topics such as epidemic severity and vaccination are changing the way in which we perceive the utility of disease prevention. Voluntary influenza vaccination has been recently modeled using inductive reasoning games. It has thus been found that severe epidemics may occur because individuals do not vaccinate and, instead, attempt to benefit from the immunity of their peers. Such epidemics could be prevented by voluntary vaccination if incentives were offered. However, a key assumption has been that individuals make vaccination decisions based on whether there was an epidemic each influenza season; no other epidemiological information is available to them. In this work, we relax this assumption and investigate the consequences of making more informed vaccination decisions while no incentives are offered. We obtain three major results. First, individuals will not cooperate enough to constantly prevent influenza epidemics through voluntary vaccination no matter how much they learned about influenza epidemiology. Second, broadcasting epidemiological information richer than whether an epidemic occurred may stabilize the vaccination coverage and suppress severe influenza epidemics. Third, the stable vaccination coverage follows the trend of the perceived benefit of vaccination. However, increasing the amount of epidemiological information released to the public may either increase or decrease the perceived benefit of vaccination. We discuss three scenarios where individuals know, in addition to whether there was an epidemic, (i) the incidence, (ii) the vaccination coverage and (iii) both the incidence and the vaccination coverage, every influenza season. We show that broadcasting both the incidence and the vaccination coverage could yield either better or worse vaccination coverage than broadcasting each piece of information on its own. PMID:22205944
Kim, Yeu-Chun; Quan, Fu-Shi; Compans, Richard W; Kang, Sang-Moo; Prausnitz, Mark R
Mortality due to seasonal and pandemic influenza could be reduced by increasing the speed of influenza vaccine production and distribution. We propose that vaccination can be expedited by (1) immunizing with influenza virus-like particle (VLP) vaccines, which are simpler and faster to manufacture than conventional egg-based inactivated virus vaccines, and (2) administering vaccines using microneedle patches, which should simplify vaccine distribution due to their small package size and possible self-administration. In this study, we coated microneedle patches with influenza VLP vaccine, which was released into skin by dissolution within minutes. Optimizing the coating formulation required balancing factors affecting the coating dose and vaccine antigen stability. Vaccine stability, as measured by an in vitro hemagglutination assay, was increased by formulation with increased concentration of trehalose or other stabilizing carbohydrate compounds and decreased concentration of carboxymethylcellulose (CMC) or other viscosity-enhancing compounds. Coating dose was increased by formulation with increased VLP concentration, increased CMC concentration, and decreased trehalose concentration, as well as increased number of dip coating cycles. Finally, vaccination of mice using microneedles stabilized by trehalose generated strong antibody responses and provided full protection against high-dose lethal challenge infection. In summary, this study provides detailed analysis to guide formulation of microneedle patches coated with influenza VLP vaccine and demonstrates effective vaccination in vivo using this system.
Tseng, Yu-Fen; Weng, Tsai-Chuan; Lai, Chia-Chun; Lin, Jun-Yang; Chen, Po-Ling; Wang, Ya-Fang; Chao, Sin-Ru; Chang, Jui-Yuan; Hwang, Yi-Shiuh; Yeh, Chia-Tsui; Yu, Cheng-Ping; Chen, Yee-Chun; Su, Ih-Jen; Lee, Min-Shi
Avian-origin influenza A (H7N9) viruses emerged as human pathogens in China in early 2013 and have killed >100 persons. Influenza vaccines are mainly manufactured using egg-based technology which could not meet the surging demand during influenza pandemics. In this study, we evaluated cell-based influenza H7N9 vaccines in ferrets. An egg-derived influenza H7N9 reassortant vaccine virus was adapted in MDCK cells. Influenza H7N9 whole virus vaccine antigen was manufactured using a microcarrier-based culture system. Immunogenicity and protection of the vaccine candidates with three different formulations (300μg aluminum hydroxide, 1.5μg HA, and 1.5μg HA plus 300μg aluminum hydroxide) were evaluated in ferrets. In ferrets receiving two doses of vaccination, geometric mean titers of hemagglutination (HA) inhibition and neutralizing antibodies were <10 and <40 for the control group (adjuvant only), 17 and 80 for the unadjuvanted (HA only) group, and 190 and 640 for the adjuvanted group (HA plus adjuvant), respectively. After challenge with wild-type influenza H7N9 viruses, virus titers in respiratory tracts of the adjuvanted group were significantly lower than that in the control, and unadjuvanted groups. MDCK cell-derived influenza H7N9 whole virus vaccine candidate is immunogenic and protective in ferrets and clinical development is highly warranted. PMID:25799397
Sirinonthanawech, Naraporn; Surichan, Somchaiya; Namsai, Aphinya; Puthavathana, Pilaipan; Auewarakul, Prasert; Kongchanagul, Alita
Formulation and quality control of trivalent live-attenuated influenza vaccine requires titration of infectivity of individual strains in the trivalent mix. This is usually performed by selective neutralization of two of the three strains and titration of the un-neutralized strain in cell culture or embryonated eggs. This procedure requires standard sera with high neutralizing titer against each of the three strains. Obtaining standard sera, which can specifically neutralize only the corresponding strain of influenza viruses and is able to completely neutralize high concentration of virus in the vaccine samples, can be a problem for many vaccine manufacturers as vaccine stocks usually have very high viral titers and complete neutralization may not be obtained. Here an alternative approach for titration of individual strain in trivalent vaccine without the selective neutralization is presented. This was done by detecting individual strains with specific antibodies in an end-point titration of a trivalent vaccine in cell culture. Similar titers were observed in monovalent and trivalent vaccines for influenza A H3N2 and influenza B strains, whereas the influenza A H1N1 strain did not grow well in cell culture. Viral interference among the vaccine strains was not observed. Therefore, providing that vaccine strains grow well in cell culture, this assay can reliably determine the potency of individual strains in trivalent live-attenuated influenza vaccines.
Wright, Peter F.; Hoen, Anne G.; Ilyushina, Natalia A.; Brown, Eric P.; Ackerman, Margaret E.; Wieland-Alter, Wendy; Connor, Ruth I.; Jegaskanda, Sinthujan; Rosenberg-Hasson, Yael; Haynes, Brenda C.; Luke, Catherine J.; Subbarao, Kanta; Treanor, John J.
Background. The efficacy of live, attenuated live attenuated influenza vaccine(LAIV) and inactivated influenza vaccine(IIV) is poorly explained by either single or composite immune responses to vaccination. Protective biomarkers were therefore studied in response to LAIV or IIV followed by LAIV challenge in children. Methods. Serum and mucosal responses to LAIV or IIV were analyzed using immunologic assays to assess both quantitative and functional responses. Cytokines and chemokines were measured in nasal washes collected before vaccination, on days 2, 4, and 7 after initial LAIV, and again after LAIV challenge using a 63-multiplex Luminex panel. Results. Patterns of immunity induced by LAIV and IIV were significantly different. Serum responses induced by IIV, including hemagglutination inhibition, did not correlate with detection or quantitation of LAIV on subsequent challenge. Modalities that induced sterilizing immunity seen after LAIV challenge could not be defined by any measurements of mucosal or serum antibodies induced by the initial LAIV immunization. No single cytokine or chemokine was predictive of protection. Conclusions. The mechanism of protective immunity observed after LAIV could not be defined, and traditional measurements of immunity to IIV did not correlate with protection against an LAIV challenge. PMID:27419180
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
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.
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
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
Kon, Theone C.; Onu, Adrian; Berbecila, Laurentiu; Lupulescu, Emilia; Ghiorgisor, Alina; Kersten, Gideon F.; Cui, Yi-Qing; Amorij, Jean-Pierre; Van der Pol, Leo
The aim of this study was to evaluate the impact of different inactivation and splitting procedures on influenza vaccine product composition, stability and recovery to support transfer of process technology. Four split and two whole inactivated virus (WIV) influenza vaccine bulks were produced and compared with respect to release criteria, stability of the bulk and haemagglutinin recovery. One clarified harvest of influenza H3N2 A/Uruguay virus prepared on 25.000 fertilized eggs was divided equally over six downstream processes. The main unit operation for purification was sucrose gradient zonal ultracentrifugation. The inactivation of the virus was performed with either formaldehyde in phosphate buffer or with beta-propiolactone in citrate buffer. For splitting of the viral products in presence of Tween®, either Triton™ X-100 or di-ethyl-ether was used. Removal of ether was established by centrifugation and evaporation, whereas removal of Triton-X100 was performed by hydrophobic interaction chromatography. All products were sterile filtered and subjected to a 5 months real time stability study. In all processes, major product losses were measured after sterile filtration; with larger losses for split virus than for WIV. The beta-propiolactone inactivation on average resulted in higher recoveries compared to processes using formaldehyde inactivation. Especially ether split formaldehyde product showed low recovery and least stability over a period of five months. PMID:26959983
Kon, Theone C; Onu, Adrian; Berbecila, Laurentiu; Lupulescu, Emilia; Ghiorgisor, Alina; Kersten, Gideon F; Cui, Yi-Qing; Amorij, Jean-Pierre; Van der Pol, Leo
The aim of this study was to evaluate the impact of different inactivation and splitting procedures on influenza vaccine product composition, stability and recovery to support transfer of process technology. Four split and two whole inactivated virus (WIV) influenza vaccine bulks were produced and compared with respect to release criteria, stability of the bulk and haemagglutinin recovery. One clarified harvest of influenza H3N2 A/Uruguay virus prepared on 25.000 fertilized eggs was divided equally over six downstream processes. The main unit operation for purification was sucrose gradient zonal ultracentrifugation. The inactivation of the virus was performed with either formaldehyde in phosphate buffer or with beta-propiolactone in citrate buffer. For splitting of the viral products in presence of Tween®, either Triton™ X-100 or di-ethyl-ether was used. Removal of ether was established by centrifugation and evaporation, whereas removal of Triton-X100 was performed by hydrophobic interaction chromatography. All products were sterile filtered and subjected to a 5 months real time stability study. In all processes, major product losses were measured after sterile filtration; with larger losses for split virus than for WIV. The beta-propiolactone inactivation on average resulted in higher recoveries compared to processes using formaldehyde inactivation. Especially ether split formaldehyde product showed low recovery and least stability over a period of five months.
Pineda Solas, A; Bernaola Iturbe, E; Martinón-Torres, F; Baca Cots, M; de Juan Martín, F; Gómez Campderá, J A; Díaz Domingo, J; Garcés Sánchez, M; Giménez Sánchez, F; Picazo, J
The recommendations of the Spanish Association of Pediatrics on influenza vaccination in the pediatric age group for the 2006-2007 season are presented. Influenza has special characteristics in children due to the high morbidity it carries. Moreover, children constitute the most frequent source of transmission. The risk factors supporting influenza vaccination in children and the need for immunization in persons living with high-risk children are discussed. The advisability of extending vaccination in health workers, and specifically to pediatricians and medical personnel in contact with sick children is stressed. The composition of the vaccine for the 2006-2007 seasons, the schedules and dosages in children depending on age, and the contraindications to vaccination are specified. Finally, the premises required to recommend universal vaccination in young children in Spain as a strategy to reduce morbidity due to this epidemic in children and adults are discussed.
AI vaccines provide protection to birds, principally through mucosal and systemic humoral immunity against the HA protein and protection is HA subtype specific. Protection can be directly assessed by prevention of clinical signs and death, a decrease in number of birds infected, reduction in the qu...
Manceur, Aziza P; Kamen, Amine A
Significant improvements in production and purification have been achieved since the first approved influenza vaccines were administered 75 years ago. Global surveillance and fast response have limited the impact of the last pandemic in 2009. In case of another pandemic, vaccines can be generated within three weeks with certain platforms. However, our Achilles heel is at the quantification level. Production of reagents for the quantification of new vaccines using the SRID, the main method formally approved by regulatory bodies, requires two to three months. The impact of such delays can be tragic for vulnerable populations. Therefore, efforts have been directed toward developing alternative quantification methods, which are sensitive, accurate, easy to implement and independent of the availability of specific reagents. The use of newly-developed antibodies against a conserved region of hemagglutinin (HA), a surface protein of influenza, holds great promises as they are able to recognize multiple subtypes of influenza; these new antibodies could be used in immunoassays such as ELISA and slot-blot analysis. HA concentration can also be determined using reversed-phase high performance liquid chromatography (RP-HPLC), which obviates the need for antibodies but still requires a reference standard. The number of viral particles can be evaluated using ion-exchange HPLC and techniques based on flow cytometry principles, but non-viral vesicles have to be taken into account with cellular production platforms. As new production systems are optimized, new quantification methods that are adapted to the type of vaccine produced are required. The nature of these new-generation vaccines might dictate which quantification method to use. In all cases, an alternative method will have to be validated against the current SRID assay. A consensus among the scientific community would have to be reached so that the adoption of new quantification methods would be harmonized between
El Masry, Ihab; Rijks, Jolianne; Peyre, Marisa; Taylor, Nick; Lubroth, Juan; Jobre, Yilma
Highly pathogenic avian influenza (AI) due to H5N1 virus was first reported in Egypt in February 2006; since then, the government has allowed avian influenza vaccination in poultry. The present study evaluated the impact of AI vaccination in terms of cumulative annual flock immunity (CAFI): the percentage of bird × weeks protected by immunity. This evaluation took account of the combined effects of vaccination coverage, vaccine efficacy (VE), and different characteristics of household poultry production on the effectiveness of the adopted vaccination strategy (VS), and provided alternative options for improvement. The evaluation used a population and vaccination model that calculates the CAFI. Participatory approaches were employed in 21 villages to develop the vaccination and flock parameters required for the model. The adopted VS were compared in the model with three alternative VS scenarios in terms of the CAFI. Vaccination coverage varied among villages but was generally low (between 1 and 48 %; median 14 %). Under the adopted VS, the CAFI predicted for the villages ranged from 2 to 31 %. It was concluded that despite the enormous effort put into rural household poultry AI vaccination by the Egyptian government, village CAFI is unlikely to be maintained at the levels required to significantly reduce the virus load and restrict transmission. In HPAI-endemic countries that consider AI vaccination as one of the disease control options, the high cost of mass AI vaccination campaigns and their achievable benefits must be compared with other available control measures, which may include targeted vaccination. Achievable vaccination coverage, VE and the different characteristics of commercial and household (village) poultry production are key parameters determining the feasibility and cost-effectiveness of different AI vaccination strategies.
Wang, Ji; Li, Bo; Wu, Mei X.
The current study details efficient lesion-free cutaneous vaccination via vaccine delivery into an array of micropores in the skin, instead of bolus injection at a single site. Such delivery effectively segregated vaccine-induced inflammation, resulting in rapid resolution of the inflammation, provided that distances between any two micropores were sufficient. When the inoculation site was treated by FDA-approved nonablative fractional laser (NAFL) before insertion of a PR8 model influenza vaccine-packaged, biodegradable microneedle array (MNs), mice displayed vigorous antigen-uptake, eliciting strong Th1-biased immunity. These animals were completely protected from homologous viral challenges, and fully or partially protected from heterologous H1N1 and H3N2 viral challenges, whereas mice receiving MNs alone suffered from severe illnesses or died of similar viral challenges. NAFL-mediated adjuvanicity was ascribed primarily to dsDNA and other “danger” signals released from laser-damaged skin cells. Thus, mice deficient in dsDNA-sensing pathway, but not Toll like receptor (TLR) or inflammasome pathways, showed poor responses to NAFL. Importantly, with this novel approach both mice and swine exhibited strong protective immunity without incurring any appreciable skin irritation, in sharp contrast to the overt skin irritation caused by intradermal injections. The effective lesion-free cutaneous vaccination merits further clinical studies. PMID:25848020
LAIV) to inactivated influenza vaccine (TIV) among adults . To compare the incidence of influenza-like illness following immu- nization of adultswith...influenza vaccine (LAIV) has been licensed for use in children and adults in the U.S. since 2003. The vac- cine, which is administered intranasally...challenge studies, have been conducted among adults . Although both vaccines have been shown to have absolute effec- tiveness against influenza-like
Sheridan, Patricia A.; Paich, Heather A.; Handy, Jean; Karlsson, Erik A.; Schultz-Cherry, Stacey; Hudgens, Michael; Weir, Sam; Noah, Terry; Beck, Melinda A.
Background Diabetics are considered to be at high risk for complications from influenza infection and Type 2 diabetes is a significant comorbidity of obesity. Obesity is an independent risk factor for complications from infection with influenza. Annual vaccination is considered the best strategy for protecting against influenza infection and it’s complications. Our previous study reported intact antibody responses 30 days post vaccination in an obese population. This study was designed to determine the antibody response to influenza vaccination in type 2 diabetics. Methods Subjects enrolled were 18 or older without immunosuppressive diseases or taking immunosuppressive medications. A pre-vaccination blood draw was taken at time of enrollment, the subjects received the influenza vaccine and returned 28–32 days later for a post-vaccination blood draw. Height and weight were also obtained at the first visit and BMI was calculated. Antibody levels to the vaccine were determined by both ELISA and hemagglutination inhibition (HAI) assays. Results As reported in our previous work, obesity positively correlates with the influenza antibody response (p=0.02), while age was negatively correlated with antibody response (p<0.001). In both year 1 and year 2 of our study there was no significant difference in the percentage of the type 2 diabetic subjects classified as seroprotected or a responder to the influenza vaccine compared to the non-diabetic subjects. Conclusions These data are important because they demonstrate that diabetics, considered a high risk group during influenza season, are able to mount an antibody response to influenza vaccination that may protect them from influenza infection. PMID:26044491
Valenciano, Marta; Kissling, Esther; Cohen, Jean-Marie; Oroszi, Beatrix; Barret, Anne-Sophie; Rizzo, Caterina; Nunes, Baltazar; Pitigoi, Daniela; Larrauri Cámara, Amparro; Mosnier, Anne; Horvath, Judith K.; O'Donnell, Joan; Bella, Antonino; Guiomar, Raquel; Lupulescu, Emilia; Savulescu, Camelia; Ciancio, Bruno C.; Kramarz, Piotr; Moren, Alain
Background A multicentre case-control study based on sentinel practitioner surveillance networks from seven European countries was undertaken to estimate the effectiveness of 2009–2010 pandemic and seasonal influenza vaccines against medically attended influenza-like illness (ILI) laboratory-confirmed as pandemic influenza A (H1N1) (pH1N1). Methods and Findings Sentinel practitioners swabbed ILI patients using systematic sampling. We included in the study patients meeting the European ILI case definition with onset of symptoms >14 days after the start of national pandemic vaccination campaigns. We compared pH1N1 cases to influenza laboratory-negative controls. A valid vaccination corresponded to >14 days between receiving a dose of vaccine and symptom onset. We estimated pooled vaccine effectiveness (VE) as 1 minus the odds ratio with the study site as a fixed effect. Using logistic regression, we adjusted VE for potential confounding factors (age group, sex, month of onset, chronic diseases and related hospitalizations, smoking history, seasonal influenza vaccinations, practitioner visits in previous year). We conducted a complete case analysis excluding individuals with missing values and a multiple multivariate imputation to estimate missing values. The multivariate imputation (n = 2902) adjusted pandemic VE (PIVE) estimates were 71.9% (95% confidence interval [CI] 45.6–85.5) overall; 78.4% (95% CI 54.4–89.8) in patients <65 years; and 72.9% (95% CI 39.8–87.8) in individuals without chronic disease. The complete case (n = 1,502) adjusted PIVE were 66.0% (95% CI 23.9–84.8), 71.3% (95% CI 29.1–88.4), and 70.2% (95% CI 19.4–89.0), respectively. The adjusted PIVE was 66.0% (95% CI −69.9 to 93.2) if vaccinated 8–14 days before ILI onset. The adjusted 2009–2010 seasonal influenza VE was 9.9% (95% CI −65.2 to 50.9). Conclusions Our results suggest good protection of the pandemic monovalent vaccine against medically attended pH1N1 and no
Dunning, Andrew J; DiazGranados, Carlos A; Voloshen, Timothy; Hu, Branda; Landolfi, Victoria A; Talbot, H Keipp
Although a number of studies have investigated and quantified immune correlates of protection against influenza in adults and children, data on immune protection in the elderly are sparse. A recent vaccine efficacy trial comparing standard-dose with high-dose inactivated influenza vaccine in persons 65 years of age and older provided the opportunity to examine the relationship between values of three immunologic assays and protection against community-acquired A/H3N2 influenza illness. The high-dose vaccine induced significantly higher antibody titers than the standard-dose vaccine for all assays. For the hemagglutination inhibition assay, a titer of 40 was found to correspond with 50% protection when the assay virus was antigenically well matched to the circulating virus--the same titer as is generally recognized for 50% protection in younger adults. A dramatically higher titer was required for 50% protection when the assay virus was a poor match to the circulating virus. With the well-matched virus, some protection was seen at the lowest titers; with the poorly matched virus, high levels of protection were not achieved even at the highest titers. Strong associations were also seen between virus neutralization test titers and protection, but reliable estimates for 50% protection were not obtained. An association was seen between titers of an enzyme-linked lectin assay for antineuraminidase N2 antibodies and protection; in particular, the proportion of treatment effect explained by assay titer in models that included both this assay and one of the other assays was consistently higher than in models that included either assay alone. (This study has been registered at ClinicalTrials.gov under registration no. NCT01427309.).
The rightfulness and relevance of the use of fear appeals in prevention are not debated in France. However, it seems that the recent failure of the H1N1 influenza vaccination, following many political and journalistic speeches mainly focused on the fear of the illness and its consequences, should challenge policy-makers about the choice of this communication means. Other methods, founded on the results of an "emotional epidemiology" of the epidemic and based on community health approaches, could have been usefully applied.
Håberg, Siri E; Trogstad, Lill; Gunnes, Nina; Wilcox, Allen J.; Gjessing, Håkon K.; Samuelsen, Sven Ove; Skrondal, Anders; Cappelen, Inger; Engeland, Anders; Aavitsland, Preben; Madsen, Steinar; Buajordet, Ingebjørg; Furu, Kari; Nafstad, Per; Vollset, Stein Emil; Berit, Feiring; Nøkleby, Hanne; Magnus, Per; Stoltenberg, Camilla
Background During the 2009 influenza pandemic, pregnant women were at particular risk of serious influenza illness. This concern was further complicated by questions about vaccine safety in pregnant women raised by anecdotal reports of fetal deaths following vaccination. Methods We explored the safety of influenza vaccination of pregnant women by linking Norwegian national registries and medical consultation data to determine influenza diagnosis, vaccination status, birth outcomes, and background information for pregnant women before, during, and after the pandemic. We used Cox regression models to estimate hazard ratios of fetal death, with gestational day as the time metric and vaccination and pandemic exposure as time-dependent exposure variables. Results There were 117,347 eligible pregnancies in Norway in 2009–2010. Fetal mortality was 4.9/1000. 54% of pregnant women in their second or third trimester during the pandemic were vaccinated. Vaccination in pregnancy substantially reduced the risk of influenza diagnosis (adjusted hazard ratio, 0.30; 95% confidence interval [CI], 0.25 to 0.34). A clinical diagnosis of influenza in the mother increased the risk of fetal death (adjusted hazard ratio, 1.91; 95% CI, 1.07 to 3.41). Among pregnant women, the risk of fetal death was lower with vaccination, although this reduction was not statistically significant (adjusted hazard ratio, 0.88; 95% CI, 0.66 to 1.17). Conclusions Pandemic influenza in pregnancy was associated with increased risk of fetal death. Vaccination during pregnancy reduced the risk of influenza diagnosis. Vaccination itself did not increase fetal mortality, and may have reduced the risk of influenza-related fetal death during the pandemic. PMID:23323868
Fonseca, Wendy; Ozawa, Makoto; Hatta, Masato; Orozco, Esther; Martínez, Máximo B; Kawaoka, Yoshihiro
Infections with influenza and respiratory syncytial virus (RSV) rank high among the most common human respiratory diseases worldwide. Previously, we developed a replication-incompetent influenza virus by replacing the coding sequence of the PB2 gene, which encodes one of the viral RNA polymerase subunits, with that of a reporter gene. Here, we generated a PB2-knockout recombinant influenza virus expressing the F protein of RSV (PB2-RSVF virus) and tested its potential as a bivalent vaccine. In mice intranasally immunized with the PB2-RSVF virus, we detected high levels of antibodies against influenza virus, but not RSV. PB2-RSVF virus-immunized mice were protected from a lethal challenge with influenza virus but experienced severe body weight loss when challenged with RSV, indicating that PB2-RSVF vaccination enhanced RSV-associated disease. These results highlight one of the difficulties of developing an effective bivalent vaccine against influenza virus and RSV infections. PMID:24292020
Artiaga, Bianca L.; Yang, Guan; Hackmann, Timothy J.; Liu, Qinfang; Richt, Jürgen A.; Salek-Ardakani, Shahram; Castleman, William L.; Lednicky, John A.; Driver, John P.
Natural killer T (NKT) -cells activated with the glycolipid ligand α-galactosylceramide (α-GalCer) stimulate a wide array of immune responses with many promising immunotherapeutic applications, including the enhancement of vaccines against infectious diseases and cancer. In the current study, we evaluated whether α-GalCer generates protective immunity against a swine influenza (SI) virus infection when applied as an intramuscular vaccine adjuvant. Immunization of newly weaned piglets with UV-killed pandemic H1N1 A/California/04/2009 (kCA04) SI virus and α-GalCer induced high titers of anti-hemagglutinin antibodies and generated virus-specific T cells that localized in intrapulmonary airways and in alveolar walls. Vaccination with α-GalCer resulted in a systemic increase in NKT-cell concentrations, including in the respiratory tract, which was associated with complete inhibition of viral replication in the upper and lower respiratory tract and much reduced viral shedding. These results indicate that NKT-cell agonists could be used to improve swine vaccine formulations in order to reduce the clinical signs of SI infection and limit the spread of influenza viruses amongst commercial pigs. PMID:27004737
Flood, Alexander; Chen, Dexiang
An influenza pandemic remains a major public health concern. A key strategy to prevent a pandemic is to stockpile and pre-position stable influenza vaccine to allow rapid deployment in response to an outbreak. However, most influenza vaccines today are formulated as liquids that are stable only within a temperature range of 2°C to 8°C and require use of a cold chain, making vaccine transportation, distribution, and storage complicated and expensive, particularly for developing countries. To support the National Strategy for Pandemic Influenza preparedness in the United States and internationally, we developed two lead dry formulations of stable H1N1 influenza subunit vaccines using freeze-drying technology. The stable formulations contain an excipient combination of a disaccharide, such as sucrose or trehalose, and glycine, in addition to a surfactant and phosphate buffer. The freeze-dried vaccines were shown to be safe and remained immunogenic in an in vivo study in mice. Moreover, the lead formulations demonstrated no significant loss of activity after 40 months at storage temperatures of 25°C and 37°C. This stability can be particularly attractive as it could eliminate the need to use a cold chain for vaccine deployment and facilitate integration of vaccine distribution with general drug distribution where appropriate. These freeze-dried thermostable influenza subunit vaccines could also reduce the frequency of vaccine stockpile turnover, offering a cost-effective option for pandemic preparedness. PMID:27851765
Shono, Aiko; Kondo, Masahide
In Japan, trivalent inactivated influenza vaccine is the only approved influenza vaccine. It is typically administrated by hypodermic injection, and children under 13 years of age are recommended to be vaccinated two times during each winter season. Live-attenuated influenza vaccine (LAIV) is administered by a thimerosal-free nasal spray. If LAIV is approved in the future in Japan, parents will have an alternative type of influenza vaccine for their children. This study investigated parents' preference for the type of seasonal influenza vaccine for their children if alternatives are available. The marginal willingness to pay for vaccine benefits was also evaluated. We conducted a discrete choice experiment, a quantitative approach that is often used in healthcare studies, in January 2013. Respondents were recruited from a registered online survey panel, and parents with at least one child under 13 years of age were offered questionnaires. This study showed that for seasonal influenza vaccines for their children, parents are more likely to value safety, including thimerosal-free vaccines and those with a lower risk of adverse events, instead of avoiding the momentary pain from an injection. If LAIV is released in Japan, the fact that it is thimerosal-free could be an advantage. However, for parents to choose LAIV, they would need to accept the slightly higher risk of minor adverse events from LAIV.
Wong, Chinn Yi; Mifsud, Edin J.; Edenborough, Kathryn M.; Sekiya, Toshiki; Tan, Amabel C. L.; Mercuri, Francesca; Rockman, Steve; Chen, Weisan; Turner, Stephen J.; Doherty, Peter C.; Kelso, Anne; Brown, Lorena E.; Jackson, David C.
ABSTRACT The continual threat to global health posed by influenza has led to increased efforts to improve the effectiveness of influenza vaccines for use in epidemics and pandemics. We show in this study that formulation of a low dose of inactivated detergent-split influenza vaccine with a Toll-like receptor 2 (TLR2) agonist-based lipopeptide adjuvant (R4Pam2Cys) provides (i) immediate, antigen-independent immunity mediated by the innate immune system and (ii) significant enhancement of antigen-dependent immunity which exhibits an increased breadth of effector function. Intranasal administration of mice with vaccine formulated with R4Pam2Cys but not vaccine alone provides protection against both homologous and serologically distinct (heterologous) viral strains within a day of administration. Vaccination in the presence of R4Pam2Cys subsequently also induces high levels of systemic IgM, IgG1, and IgG2b antibodies and pulmonary IgA antibodies that inhibit hemagglutination (HA) and neuraminidase (NA) activities of homologous but not heterologous virus. Improved primary virus nucleoprotein (NP)-specific CD8+ T cell responses are also induced by the use of R4Pam2Cys and are associated with robust recall responses to provide heterologous protection. These protective effects are demonstrated in wild-type and antibody-deficient animals but not in those depleted of CD8+ T cells. Using a contact-dependent virus transmission model, we also found that heterologous virus transmission from vaccinated mice to naive mice is significantly reduced. These results demonstrate the potential of adding a TLR2 agonist to an existing seasonal influenza vaccine to improve its utility by inducing immediate short-term nonspecific antiviral protection and also antigen-specific responses to provide homologous and heterologous immunity. PMID:26507227
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...
Long, Joanna E; Ring, Christopher; Drayson, Mark; Bosch, Jos; Campbell, John P; Bhabra, Jagraj; Browne, David; Dawson, Joel; Harding, Sarah; Lau, Jamie; Burns, Victoria E
High intensity acute exercise at the time of vaccination has been shown to enhance the subsequent antibody response. This study examines whether an acute moderate intensity aerobic intervention prior to vaccination can enhance antibody response to pneumonia and half dose influenza vaccination. Sixty young (age (SD)=22.0 (6.1) years) and 60 older (age (SD)=57.5 (6.5) years) adults attended the laboratory on two separate occasions. At the first session, baseline antibody titres were determined, before participants completed either a brisk walk around campus at >55% of their age-predicted heart rate maximum, or a resting control condition, for 45 min. After the intervention, all participants received a full-dose pneumococcal vaccination and a half-dose influenza vaccination. Four weeks later, participants returned for a follow up blood sample. Multivariate ANOVA revealed an increase in total antibody titres against the influenza vaccine (F((12,106))=25.76, p<.001, η(2)=.75) and both the IgM (F((12,106))=17.10, p<.001, η(2)=.66) and IgG (F((12,106))=25.76, p<.001, η(2)=.75) antibody titres against the pneumococcal vaccine. However, there were no significant Time×Group interactions (p's all >.15), indicating that a 45 min brisk walk prior to vaccination did not affect antibody response to either the influenza or pneumonia vaccine. The results suggest that higher intensity exercise is necessary to augment antibody response to vaccination.
Barr, Ian G; Jelley, Lauren L
Influenza vaccines form the mainstay of public health and personal protection against infection with seasonal influenza viruses. These vaccines are designed to protect people against infection with the currently circulating influenza viruses. Since the late 1970s, this has required the use of a trivalent vaccine consisting of two influenza A viruses and one influenza B virus. However, since the early 2000s, a second lineage of B viruses has regularly circulated in many countries that is quite distinct, with only low levels of cross protection between the two lineages. Due to the difficulties in determining which B lineage will circulate, and matching this with the vaccine to be administered some 6-9 months later, there has been an increasing interest in the development of quadrivalent influenza vaccines, containing two influenza B viruses representing both lineages. Development has been rapid and we are now on the cusp of a new generation of influenza vaccines becoming available. This paper discusses the issues and rationale behind this welcome development and who is likely to benefit most.
Gwon, Yong-Dae; Kim, Sehyun; Cho, Yeondong; Heo, Yoonki; Cho, Hansam; Park, Kihoon; Lee, Hee-Jung; Choi, Jiwon; Poo, Haryoung; Kim, Young Bong
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
Sundaram, Neisha; Purohit, Vidula; Schaetti, Christian; Kudale, Abhay; Joseph, Saju; Weiss, Mitchell G
Vaccination is a cornerstone of influenza prevention, but limited vaccine uptake was a problem worldwide during the 2009–2010 pandemic. Community acceptance of a vaccine is a critical determinant of its effectiveness, but studies have been confined to high-income countries. We conducted a cross-sectional, mixed-method study in urban and rural Pune, India in 2012–2013. Semi-structured explanatory model interviews were administered to community residents (n = 436) to study awareness, experience and preference between available vaccines for pandemic influenza. Focus group discussions and in-depth interviews complemented the survey. Awareness of pandemic influenza vaccines was low (25%). Some respondents did not consider vaccines relevant for adults, but nearly all (94.7%), when asked, believed that a vaccine would prevent swine flu. Reported vaccine uptake however was 8.3%. Main themes identified as reasons for uptake were having heard of a death from swine flu, health care provider recommendation or affiliation with the health system, influence of peers and information from media. Reasons for non-use were low perceived personal risk, problems with access and cost, inadequate information and a perceived lack of a government mandate endorsing influenza vaccines. A majority indicated a preference for injectable over nasal vaccines, especially in remote rural areas. Hesitancy from a lack of confidence in pandemic influenza vaccines appears to have been less of an issue than access, complacency and other sociocultural considerations. Recent influenza outbreaks in 2015 highlight a need to reconsider policy for routine influenza vaccination while paying attention to sociocultural factors and community preferences for effective vaccine action. PMID:26110454
Sundaram, Neisha; Purohit, Vidula; Schaetti, Christian; Kudale, Abhay; Joseph, Saju; Weiss, Mitchell G
Vaccination is a cornerstone of influenza prevention, but limited vaccine uptake was a problem worldwide during the 2009-2010 pandemic. Community acceptance of a vaccine is a critical determinant of its effectiveness, but studies have been confined to high-income countries. We conducted a cross-sectional, mixed-method study in urban and rural Pune, India in 2012-2013. Semi-structured explanatory model interviews were administered to community residents (n = 436) to study awareness, experience and preference between available vaccines for pandemic influenza. Focus group discussions and in-depth interviews complemented the survey. Awareness of pandemic influenza vaccines was low (25%). Some respondents did not consider vaccines relevant for adults, but nearly all (94.7%), when asked, believed that a vaccine would prevent swine flu. Reported vaccine uptake however was 8.3%. Main themes identified as reasons for uptake were having heard of a death from swine flu, health care provider recommendation or affiliation with the health system, influence of peers and information from media. Reasons for non-use were low perceived personal risk, problems with access and cost, inadequate information and a perceived lack of a government mandate endorsing influenza vaccines. A majority indicated a preference for injectable over nasal vaccines, especially in remote rural areas. Hesitancy from a lack of confidence in pandemic influenza vaccines appears to have been less of an issue than access, complacency and other sociocultural considerations. Recent influenza outbreaks in 2015 highlight a need to reconsider policy for routine influenza vaccination while paying attention to sociocultural factors and community preferences for effective vaccine action.
Genetic and antigenic diversity within H1 influenza A virus (IAV) subtypes circulating in swine is increasing. The need for cross-protective influenza vaccines in swine is necessary as the virus becomes more diverse. This study compared the humoral and cell-mediated immune response of modified live ...
Weil-Olivier, Catherine; Lina, Bruno
For a number of years now, GEIG, the Groupement d'Expertise et d'Information sur la Grippe (Influenza Expertise and Information Group) has conducted surveys to monitor seasonal trivalent vaccine uptake in France in adults. During the H1N1 pandemic in 2009, this survey was conducted to determine vaccination uptake for both pandemic and seasonal vaccines. An additional specific questionnaire was used to collect data on vaccination in children under 15 years of age. This additional study was carried out because pandemic vaccination (PV) was offered to the French population and children were listed as a priority target group by the national health authorities, whereas seasonal trivalent inactivated vaccines (TIV) are not recommended in children in France. Overall, we collected 2443 questionnaires on children, including children with underlying conditions (9.2%) for whom TIV vaccination was recommended. Overall, 17.9% of children (438/2443) received at least one shot of PV, compared to 3.4% (83/2443) who received at least one shot of TIV. PV uptake was statistically different between non at-risk and at-risk children (366/2218 [16.5%] vs. 71/225 [31.8%], p<0.0001). This difference was even more significant in the subgroup of children with severe underlying diseases (42.7%, p<0.0001). This confirms that despite the low overall PV uptake in the French population (9%), the specific recommendation for PV for children increased vaccine uptake in this specific population, suggesting that the disease burden of influenza in children is recognised by both practitioners and parents. The next few years will tell us whether TIV uptake in children increases as a consequence of the specific recommendations made for children during the 2009 pandemic wave, or whether it will return to the very low level of 3.4% observed before the pandemic.
Wiley, Kerrie E; Cooper, Spring C; Wood, Nicholas; Leask, Julie
Internationally, pregnant and postpartum women have been the focus of influenza and pertussis immunization campaigns, with differing levels of vaccine acceptance. We used semistructured interviews to explore pregnant women's perspectives on influenza vaccination during pregnancy and postpartum pertussis vaccination. Many women saw pregnancy as a busy time filled with advice on what they "should" and "should not" do to ensure the health of their fetus, and vaccinating themselves was regarded as just one of these tasks needing consideration. Women were more concerned about potential risks to their infants' health before their own. They saw influenza as a disease affecting the mother, whereas they viewed pertussis as a threat to the baby and therefore comparatively more risky. They were thus more likely to intend to vaccinate against pertussis to protect their infant. Framing of vaccination information toward protection of the baby might help increase vaccine uptake among pregnant women.
Manske, Jill M
Influenza vaccine is universally recommended for pregnant women during any trimester of pregnancy. In light of this recommendation, a comprehensive literature review was conducted to examine the available evidence regarding influenza vaccine efficacy and effectiveness during pregnancy. A comprehensive Medline search identified potentially relevant articles published between January 1, 1964 and February 1, 2013. Articles were selected that specifically evaluated the efficacy and effectiveness of maternal influenza vaccine in protecting women and infants from influenza infection. These were reviewed with a particular focus on the methods used to confirm influenza infection. Ten of 476 articles met the inclusion criteria. None of the six studies evaluating maternal outcomes were randomized controlled studies using a laboratory-confirmed influenza diagnosis to measure vaccine efficacy. Two studies included reverse-transcriptase polymerase chain reaction confirmation; four relied solely on clinical outcomes. The reported vaccine effectiveness (VE) ranged from -15 to 70 %. Seven studies examined the potential for maternal vaccination to protect infants. Four of these applied some form of laboratory confirmation, with VE ranging from 41 to 91 %. Vaccination against infectious disease is an unparalleled public health success. However, studies to date demonstrate that influenza vaccine provides only moderate protection from influenza infection in pregnant women. This review found broad heterogeneity among studies, with no uniform outcome measured and little data based on laboratory-confirmed influenza, leading to wide-ranging estimates of effectiveness. Rigorously designed studies assessing clearly defined outcomes are needed to support the development of reasoned public health policy about influenza prevention in this population.
Because influenza can be especially severe during pregnancy, the American College of Obstetricians and Gynecologists (ACOG) and the Advisory Committee on Immunization Practices (ACIP) recommend influenza vaccination for women who will be pregnant during the influenza season, regardless of trimester. During the 2009-10 influenza season, pregnant women were at increased risk for severe disease and mortality from influenza A (H1N1)pdm09 (pH1N1) pandemic virus infection. Anticipating this risk, both the inactivated trivalent seasonal and monovalent pH1N1 vaccinations were recommended for pregnant women. To estimate state-specific seasonal and pH1N1 influenza vaccination coverage among pregnant women, CDC analyzed data from the Pregnancy Risk Assessment Monitoring System (PRAMS). This report provides estimates from 29 states and New York City (NYC) for women who had live births during September 2009-May 2010. Median state coverage was 47.1% for seasonal and 40.4% for pH1N1 influenza vaccination. Overall, women who reported that a health-care provider offered them influenza vaccination or told them to get it during their pregnancy were more likely to be vaccinated than those without an offer or recommendation (prevalence ratio [PR] = 5.2 for seasonal, and PR = 14.4 for pH1N1). Substantial variation across areas was observed for prevalence of a provider offer or recommendation during pregnancy and for influenza vaccination. These findings highlight the need for state-specific strategies that optimize provider involvement to increase influenza vaccination of pregnant women.
Domínguez, Angela; Castilla, Jesús; Godoy, Pere; Delgado-Rodríguez, Miguel; Saez, Marc; Soldevila, Núria; Astray, Jenaro; Mayoral, José María; Martín, Vicente; Quintana, José María; González-Candelas, Fernando; Galán, Juan Carlos; Tamames, Sonia; Castro, Ady; Baricot, Maretva; Garín, Olatz; Pumarola, Tomas; Working Group (Spain), CIBERESP Cases and Controls in Pandemic Influenza
Background: Since influenza predisposes to bacterial pneumonia caused by Streptococcus pneumoniae, studies have suggested that pneumococcal vaccination might reduce its occurrence during pandemics. We assessed the effectiveness of pneumococcal polysaccharide vaccination alone and in combination with influenza vaccination in preventing influenza hospitalization during the 2009–2010 pandemic wave and 2010–2011 influenza epidemic. Methods: We conducted a multicenter case-control study in 36 Spanish hospitals. We selected patients aged ≥ 18 y hospitalized with confirmed influenza and two hospitalized controls per case, matched according to age, date of hospitalization and province of residence. Multivariate analysis was performed using conditional logistic regression. Subjects were considered vaccinated if they had received the pneumococcal or seasonal influenza vaccine > 14 d (or > 7 d for pandemic influenza vaccine) before the onset of symptoms (cases) or the onset of symptoms in matched cases (controls). Results: 1187 cases and 2328 controls were included. The adjusted estimate of effectiveness of pneumococcal vaccination in preventing influenza hospitalization was 41% (95% CI 8–62) in all patients and 43% (95% CI 2–78) in patients aged ≥ 65 y. The adjusted effectiveness of dual PPV23 and influenza vaccination was 81% (95% CI 65–90) in all patients and 76% (95% CI 46–90) in patients aged ≥ 65 y. The adjusted effectiveness of influenza vaccination alone was 58% (95% CI 38–72). Conclusions: In elderly people and adults with chronic illness, pneumococcal vaccination may reduce hospitalizations during the influenza season. In people vaccinated with both the influenza and pneumococcal vaccines, the benefit in hospitalizations avoided was greater than in those vaccinated only against influenza. PMID:23563516
Le, Phuc; Griffiths, Ulla K.; Anh, Dang Duc; Franzini, Luisa; Chan, Wenyaw; Swint, J. Michael
Background With GAVI support, Vietnam introduced Haemophilus influenzae type b (Hib) vaccine in 2010 without evidence on cost-effectiveness. We aimed to analyze the cost-effectiveness of Hib vaccine from societal and governmental perspectives. Method We constructed a decision-tree cohort model to estimate the costs and effectiveness of Hib vaccine versus no Hib vaccine for the 2011 birth cohort. The disease burden was estimated from local epidemiologic data and literature. Vaccine delivery costs were calculated from governmental reports and 2013 vaccine prices. A prospective cost-of-illness study was conducted to estimate treatment costs. The human capital approach was employed to estimate productivity loss. The incremental costs of Hib vaccine were divided by cases, deaths, and disability-adjusted life years (DALY) averted. We used the WHO recommended cost-effectiveness thresholds of an intervention being highly cost-effective if incremental costs per DALY were below GDP per capita. Result From the societal perspective, incremental costs per discounted case, death and DALY averted were US$ 6,252, US$ 26,476 and US$ 1,231, respectively; the break-even vaccine price was US$ 0.69/dose. From the governmental perspective, the results were US$ 6,954, US$ 29,449, and US$ 1,373, respectively; the break-even vaccine price was US$ 0.48/dose. Vietnam's GDP per capita was US$ 1,911 in 2013. In deterministic sensitivity analysis, morbidity and mortality parameters were among the most influential factors. In probabilistic sensitivity analysis, Hib vaccine had an 84% and 78% probability to be highly cost-effective from the societal and governmental perspectives, respectively. Conclusion Hib vaccine was highly cost-effective from both societal and governmental perspectives. However, with GAVI support ending in 2016, the government will face a six-fold increase in its vaccine budget at the 2013 vaccine price. The variability of vaccine market prices adds an element of uncertainty
Development of vaccines for effective control of avian influenza (AI) virus in poultry and wild birds is in high demand. Most AI vaccines target the immunodominant antigens such as hemagglutinin (HA) and neuraminidase (NA); however, these vaccines only provide protection against a particular AI ser...
Immunosuppressive viruses are known to affect vaccinal immunity, however the impact of virally induced immunosuppression on avian influenza vaccine efficacy has not been quantified. In order to determine the effect of exposure to infectious bursal disease virus (IBDV) on vaccinal immunity to highly ...
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
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.
The immune system normally protects the human host against death by infection. I will introduce a physical theory of the evolutionary dynamics that occurs in the antibody-mediated and T cell-mediated immune responses. The theory will be used to provide a mechanism for original antigenic sin, wherein an initial exposure to antigen can degrade the response of the immune system upon subsequent exposure to related, but different, antigens. A new order parameter to characterize antigenic distance will be introduced from the theory. This order parameter predicts effectiveness of the influenza vaccine more reliably than do results from animal model studies currently used by world health authorit