Østerhus, Sven Frederick
The Cochrane Library was systematically searched for meta-analyses regarding influenza vaccination of various populations, both healthy and sick. An effect in reducing the number of cases of influenza, influenza-like illness or complications to influenza was found in some studies, but, generally......, the quality of the studies was low, and several studies lacked hard clinical endpoints. Data on adverse effects were scarce. More randomised controlled trials investigating the effects of influenza vaccination are warranted....
L.A. Reperant (Leslie); G.F. Rimmelzwaan (Guus); A.D.M.E. Osterhaus (Albert)
textabstractInfluenza virus infections yearly cause high morbidity and mortality burdens in humans, and the development of a new influenza pandemic continues to threaten mankind as a Damoclean sword. Influenza vaccines have been produced by using egg-based virus growth and passaging techniques that
Full Text Available 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 21st century underlined the urgent need to develop new vaccines capable of protection 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 recognising conserved antigens are a key contributor to 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.
Conclusions: Controlled human infection studies are an important research tool in assessing promising influenza vaccines and antivirals. These studies are performed quickly and are cost-effective and safe, with a low incidence of serious adverse events.
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
Marshall K. Cheney
Full Text Available Yearly influenza vaccination continues to be underutilized by those who would most benefit from it. The Health Belief Model was used to explain differences in beliefs about influenza vaccination among at-risk individuals resistant to influenza vaccination. Survey data were collected from 74 members of at-risk groups who were not vaccinated for influenza during the previous flu season. Accepting individuals were more likely to perceive flu as a threat to health and perceive access barriers, and cues to action were the most important influence on whether they plan to get vaccinated. In comparison, resistant individuals did not feel threatened by the flu, access barriers were not a problem, and they did not respond favorably to cues to action. Perceived threat, perceived access barriers, and cues to action were significantly associated with plans to be vaccinated for influenza in the next flu season. Participants who saw influenza as a threat to their health had 5.4 times the odds of planning to be vaccinated than those who did not. Participants reporting barriers to accessing influenza vaccination had 7.5 times the odds of reporting plans to be vaccinated. Those responding positively to cues to action had 12.2 times the odds of planning to be vaccinated in the next flu season than those who did not. Accepting and resistant individuals have significant differences in their beliefs, which require different intervention strategies to increase vaccination rates. These findings provide important information to researchers and practitioners working to increase influenza vaccination rates.
Amorij, Jean-Pierre; Hinrichs, Wouter L.J.; Frijlink, Henderik W.; Wilschut, Jan C.; Huckriede, Anke
Vaccination is the cornerstone of influenza control in epidemic and pandemic situations. Influenza vaccines are typically given by intramuscular injection. However, needle-free vaccinations could offer several distinct advantages over intramuscular injections: they are pain-free, easier to
Kubota-Koketsu, Ritsuko; Mizuta, Hiroyuki [Department of Virology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871 (Japan); Oshita, Masatoshi; Ideno, Shoji [Osaka Research Laboratory, Benesis Corporation, Yodogawa-ku, Osaka 532-6505 (Japan); Yunoki, Mikihiro [Osaka Research Laboratory, Benesis Corporation, Yodogawa-ku, Osaka 532-6505 (Japan); Department of Virology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871 (Japan); Kuhara, Motoki [Ina Laboratory, Medical and Biological Laboratories Corporation, Ltd., Ina, Nagano 396-0002 (Japan); Yamamoto, Naomasa [Department of Biochemistry, School of Pharmaceutical Sciences, Ohu University, Koriyama, Fukushima 963-8611 (Japan); Okuno, Yoshinobu [Kanonji Institute, The Research Foundation for Microbial Diseases of Osaka University, Kanonji, Kagawa 768-0061 (Japan); Ikuta, Kazuyoshi, E-mail: firstname.lastname@example.org [Department of Virology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871 (Japan)
Human monoclonal antibodies (HuMAbs) prepared from patients with viral infections could provide information on human epitopes important for the development of vaccines as well as potential therapeutic applications. Through the fusion of peripheral blood mononuclear cells from a total of five influenza-vaccinated volunteers, with newly developed murine-human chimera fusion partner cells, named SPYMEG, we obtained 10 hybridoma clones stably producing anti-influenza virus antibodies: one for influenza A H1N1, four for influenza A H3N2 and five for influenza B. Surprisingly, most of the HuMAbs showed broad reactivity within subtype and four (two for H3N2 and two for B) showed broad neutralizing ability. Importantly, epitope mapping revealed that the two broad neutralizing antibodies to H3N2 derived from different donors recognized the same epitope located underneath the receptor-binding site of the hemagglutinin globular region that is highly conserved among H3N2 strains.
Kubota-Koketsu, Ritsuko; Mizuta, Hiroyuki; Oshita, Masatoshi; Ideno, Shoji; Yunoki, Mikihiro; Kuhara, Motoki; Yamamoto, Naomasa; Okuno, Yoshinobu; Ikuta, Kazuyoshi
Human monoclonal antibodies (HuMAbs) prepared from patients with viral infections could provide information on human epitopes important for the development of vaccines as well as potential therapeutic applications. Through the fusion of peripheral blood mononuclear cells from a total of five influenza-vaccinated volunteers, with newly developed murine-human chimera fusion partner cells, named SPYMEG, we obtained 10 hybridoma clones stably producing anti-influenza virus antibodies: one for influenza A H1N1, four for influenza A H3N2 and five for influenza B. Surprisingly, most of the HuMAbs showed broad reactivity within subtype and four (two for H3N2 and two for B) showed broad neutralizing ability. Importantly, epitope mapping revealed that the two broad neutralizing antibodies to H3N2 derived from different donors recognized the same epitope located underneath the receptor-binding site of the hemagglutinin globular region that is highly conserved among H3N2 strains.
Infections with the influenza virus and Streptococcus pneumoniae are associated with ... .well as the potential benefit and the safety of the vaccine ..... 4.6 Antiviral agents for influenza A2 ... persons who are to travel to other areas, e.g. northern.
Full Text Available BACKGROUND: The virus-specific cytotoxic T lymphocyte (CTL induction is an important target for the development of a broadly protective human influenza vaccine, since most CTL epitopes are found on internal viral proteins and relatively conserved. In this study, the possibility of developing a strain/subtype-independent human influenza vaccine was explored by taking a bioinformatics approach to establish an immunogenic HLA-A24 restricted CTL epitope screening system in HLA-transgenic mice. METHODOLOGY/PRINCIPAL FINDINGS: HLA-A24 restricted CTL epitope peptides derived from internal proteins of the H5N1 highly pathogenic avian influenza A virus were predicted by CTL epitope peptide prediction programs. Of 35 predicted peptides, six peptides exhibited remarkable cytotoxic activity in vivo. More than half of the mice which were subcutaneously vaccinated with the three most immunogenic and highly conserved epitopes among three different influenza A virus subtypes (H1N1, H3N2 and H5N1 survived lethal influenza virus challenge during both effector and memory CTL phases. Furthermore, mice that were intranasally vaccinated with these peptides remained free of clinical signs after lethal virus challenge during the effector phase. CONCLUSIONS/SIGNIFICANCE: This CTL epitope peptide selection system can be used as an effective tool for the development of a cross-protective human influenza vaccine. Furthermore this vaccine strategy can be applicable to the development of all intracellular pathogens vaccines to induce epitope-specific CTL that effectively eliminate infected cells.
As every year, the Medical Service is taking part in the campaign to promote vaccination against seasonal influenza. Vaccination against seasonal influenza is especially recommended for people suffering from chronic lung, cardio-vascular or kidney conditions or diabetes, for those recovering from a serious illness or surgical operation and for everyone over the age of 65. The influenza virus is transmitted by air and contact with contaminated surfaces, hence the importance of washing hands regularly with soap and / or disinfection using a hydro-alcoholic solution. From the onset of symptoms (fever> 38°, chills, cough, muscle aches and / or joint pain, fatigue) you are strongly recommended to stay at home to avoid spreading the virus. In the present context of the influenza A (H1N1) pandemic, it is important to dissociate these two illnesses and emphasise that the two viruses and the vaccines used to combat them are quite different and that protection against one will not pr...
Influenza A viruses (IAVs) are genetically diverse and variable pathogens that share various hosts including human, swine, and domestic poultry. Interspecies and intercontinental viral spreads make the ecology of IAV more complex. Beside endemic IAV infections, human has been exposed to pandemic and zoonotic threats from avian and swine influenza viruses. Animal health also has been threatened by high pathogenic avian influenza viruses (in domestic poultry) and reverse zoonosis (in swine). Considering its dynamic interplay between species, prevention and control against IAV should be conducted effectively in both humans and animal sectors. Vaccination is one of the most efficient tools against IAV. Numerous vaccines against animal IAVs have been developed by a variety of vaccine technologies and some of them are currently commercially available. We summarize several challenges in control of IAVs faced by human and animals and discuss IAV vaccines for animal use with those application in susceptible populations. PMID:29399575
... DEPARTMENT OF HEALTH AND HUMAN SERVICES Office of the Secretary Pandemic Influenza Vaccines... Secretary issued a declaration for pandemic influenza vaccines, which has been amended a number of times. The original pandemic influenza vaccine declaration was published on January 26, 2007,\\1\\ and was...
Saluja, Vinay; Hinrichs, Wouter L. J.; Frijlink, Henderik W.
Since last year influenza pandemic has struck again after 40 years, this is the right moment to discuss the different available formulation options for influenza vaccine. Looking back to the last 4 decades, most vaccines are still formulated as liquid solution. These vaccines have shown a poor
Full Text Available Nine polyvalent human influenza virus vaccines were tested by reverse transcriptase-polymerase chain reaction (RT-PCR for the presence of pestivirus RNA. Samples were selected from manufacturers in Europe and the USA. Three samples of the nine vaccines tested (33.3% gave positive results for pestivirus RNA. The 5´-untranslated genomic region sequence of the contaminant pestivirus RNA was analysed based on primary nucleotide sequence homology and on secondary sequence structures characteristic to genotypes. Two sequences belonged to Pestivirus type-1 (bovine viral diarrhoea virus [BVDV] species, genotypes BVDV-1b and BVDV-1e. These findings confirm previous reports, suggesting an improvement in preventive measures against contamination of biological products for human use.
... type="submit" value="Submit" /> Archived Flu Emails Influenza Types Seasonal Avian Swine Variant Pandemic Other Flublok Seasonal Influenza (Flu) Vaccine Questions & Answers Language: English (US) Español ...
As every year, the Medical Service is taking part in the campaign to promote vaccination against seasonal influenza. Vaccination against seasonal influenza is especially recommended for people suffering from chronic lung, cardio-vascular or kidney conditions or diabetes, for those recovering from a serious illness or surgical operation and for everyone over the age of 65. The influenza virus is transmitted by air and contact with contaminated surfaces, hence the importance of washing hands regularly with soap and / or disinfection using a hydro-alcoholic solution. From the onset of symptoms (fever> 38°, chills, cough, muscle aches and / or joint pain, fatigue) you are strongly recommended to stay at home to avoid spreading the virus. In the present context of the influenza A (H1N1) pandemic, it is important to dissociate these two illnesses and emphasise that the two viruses and the vaccines used to combat them are quite different and that protection against one will not provide protection against the...
Zimmerman, Richard K; Raviotta, Jonathan M; Nowalk, Mary Patricia; Moehling, Krissy K; Reis, Evelyn Cohen; Humiston, Sharon G; Lin, Chyongchiou Jeng
To report the results of an intervention using the 4 Pillars™ Practice Transformation Program (4 Pillars™ Program) to increase adolescent vaccinations including human papillomavirus vaccine (HPV) and influenza vaccines, which remain underutilized in this population. Eleven pediatric and family medicine practices, previously control sites from a randomized controlled cluster trial, with ≥50 adolescent patients participated. The 4 Pillars™ Program was the foundation of the intervention. De-identified demographic, office visit and vaccination data were derived from electronic medical record extractions for patients whose date of birth was 4/1/1997 to 4/1/2004 (ages 11-17years at baseline). Vaccination rates for HPV, influenza, tetanus-pertussis-diphtheria (Tdap) and meningococcal (MenACWY) vaccines were determined for all eligible patients pre- and post intervention (i.e., vaccination rates on 4/1/2015 and 4/30/2016). Among 9473 patients ages 11-17years at baseline (4/1/2015), mean pre-intervention vaccination rates for HPV initiation and completion, meningococcal, Tdap and influenza vaccines were below national levels. Rates increased significantly post intervention (P<0.001) for HPV initiation which increased 17.1 percentage points (PP) from 51.4%; HPV completion increased 14.8PP from 30.7%, meningococcal vaccine uptake increased 16.6PP from 79.1%, Tdap vaccine uptake increased 14.6PP from 76.9%. Influenza vaccine uptake did not increase significantly (2.3PP from 40.1%). In the regression using generalized estimating equations, odds of vaccination were higher for younger, non-white adolescents for all vaccines; being in a smaller practice decreased the odds of Tdap vaccination but increased the odds of influenza vaccination. Clinically and statistically significant improvements in HPV series initiation and completion, and meningococcal and Tdap vaccinations were observed in primary care practices implementing the 4 Pillars™ Practice Transformation Program
Hu, Weibin [Molecular Virus Unit, Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200025 (China); Chen, Aizhong [Key Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031 (China); Miao, Yi [Shanghai Xuhui Central Hospital, Shanghai 200031 (China); Xia, Shengli [Center for Disease Control and Prevention of Henan Province, Zhengzhou 450016 (China); Ling, Zhiyang; Xu, Ke; Wang, Tongyan [Molecular Virus Unit, Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200025 (China); Xu, Ying; Cui, Jun; Wu, Hongqiang; Hu, Guiyu; Tian, Lin; Wang, Lingling [Key Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031 (China); Shu, Yuelong [Chinese Center for Disease Control and Prevention, Beijing 102206 (China); Ma, Xiaowei [Hualan Biological Bacterin Company, Xinxiang 453003 (China); Xu, Bianli; Zhang, Jin [Center for Disease Control and Prevention of Henan Province, Zhengzhou 450016 (China); Lin, Xiaojun, E-mail: email@example.com [Hualan Biological Bacterin Company, Xinxiang 453003 (China); Bian, Chao, E-mail: firstname.lastname@example.org [Key Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031 (China); Sun, Bing, E-mail: email@example.com [Molecular Virus Unit, Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200025 (China); Key Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031 (China)
Whether the 2009 pandemic H1N1 influenza vaccine can induce heterosubtypic cross-protective anti-hemagglutinin (HA) neutralizing antibodies is an important issue. We obtained a panel of fully human monoclonal antibodies from the memory B cells of a 2009 pandemic H1N1 influenza vaccine recipient. Most of the monoclonal antibodies targeted the HA protein but not the HA1 fragment. Among the analyzed antibodies, seven mAbs exhibited neutralizing activity against several influenza A viruses of different subtypes. The conserved linear epitope targeted by the neutralizing mAbs (FIEGGWTGMVDGWYGYHH) is part of the fusion peptide on HA2. Our work suggests that a heterosubtypic neutralizing antibody response primarily targeting the HA stem region exists in recipients of the 2009 pandemic H1N1 influenza vaccine. The HA stem region contains various conserved neutralizing epitopes with the fusion peptide as an important one. This work may aid in the design of a universal influenza A virus vaccine.
Hu, Weibin; Chen, Aizhong; Miao, Yi; Xia, Shengli; Ling, Zhiyang; Xu, Ke; Wang, Tongyan; Xu, Ying; Cui, Jun; Wu, Hongqiang; Hu, Guiyu; Tian, Lin; Wang, Lingling; Shu, Yuelong; Ma, Xiaowei; Xu, Bianli; Zhang, Jin; Lin, Xiaojun; Bian, Chao; Sun, Bing
Whether the 2009 pandemic H1N1 influenza vaccine can induce heterosubtypic cross-protective anti-hemagglutinin (HA) neutralizing antibodies is an important issue. We obtained a panel of fully human monoclonal antibodies from the memory B cells of a 2009 pandemic H1N1 influenza vaccine recipient. Most of the monoclonal antibodies targeted the HA protein but not the HA1 fragment. Among the analyzed antibodies, seven mAbs exhibited neutralizing activity against several influenza A viruses of different subtypes. The conserved linear epitope targeted by the neutralizing mAbs (FIEGGWTGMVDGWYGYHH) is part of the fusion peptide on HA2. Our work suggests that a heterosubtypic neutralizing antibody response primarily targeting the HA stem region exists in recipients of the 2009 pandemic H1N1 influenza vaccine. The HA stem region contains various conserved neutralizing epitopes with the fusion peptide as an important one. This work may aid in the design of a universal influenza A virus vaccine.
... direct-discovery technology for use in FDA laboratories. C. Eligibility Information The technology...] Direct Discovery of HLA Associated Influenza Epitopes Isolated From Human Cells for Vaccine and... technology to molecularly characterize peptide epitopes that are processed and presented on soluble HLA...
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
Arunorat, Jirapat; Charoenvisal, Nataya; Woonwong, Yonlayong; Kedkovid, Roongtham; Jittimanee, Supattra; Sitthicharoenchai, Panchan; Kesdangsakonwut, Sawang; Poolperm, Pariwat; Thanawongnuwech, Roongroje
Since the pandemic H1N1 emergence in 2009 (pdmH1N1), many reassortant pdmH1N1 viruses emerged and found circulating in the pig population worldwide. Currently, commercial human subunit vaccines are used commonly to prevent the influenza symptom based on the WHO recommendation. In case of current reassortant swine influenza viruses transmitting from pigs to humans, the efficacy of current human influenza vaccines is of interest. In this study, influenza A negative pigs were vaccinated with selected commercial human subunit vaccines and challenged with rH3N2. All sera were tested with both HI and SN assays using four representative viruses from the surveillance data in 2012 (enH1N1, pdmH1N1, rH1N2 and rH3N2). The results showed no significant differences in clinical signs and macroscopic and microscopic findings among groups. However, all pig sera from vaccinated groups had protective HI titers to the enH1N1, pdmH1N1 and rH1N2 at 21DPV onward and had protective SN titers only to pdmH1N1and rH1N2 at 21DPV onward. SN test results appeared more specific than those of HI tests. All tested sera had no cross-reactivity against the rH3N2. Both studied human subunit vaccines failed to protect and to stop viral shedding with no evidence of serological reaction against rH3N2. SIV surveillance is essential for monitoring a novel SIV emergence potentially for zoonosis. Copyright © 2017 Elsevier Ltd. All rights reserved.
The isolation of influenza virus 80 years ago in 1933 very quickly led to the development of the first generation of live-attenuated vaccines. The first inactivated influenza vaccine was monovalent (influenza A). In 1942, a bivalent vaccine was produced after the discovery of influenza B. It was later discovered that influenza viruses mutated leading to antigenic changes. Since 1973, the WHO has issued annual recommendations for the composition of the influenza vaccine based on results from surveillance systems that identify currently circulating strains. In 1978, the first trivalent vaccine included two influenza A strains and one influenza B strain. Currently, there are two influenza B lineages circulating; in the latest WHO recommendations, it is suggested that a second B strain could be added to give a quadrivalent vaccine. The history of influenza vaccine and the associated technology shows how the vaccine has evolved to match the evolution of influenza viruses.
Full Text Available Influenza is a major respiratory pathogen causing annual outbreaks and occasional pandemics. Influenza vaccination is the major method of prophylaxis. Currently annual influenza vaccination is recommended for groups at high risk of complications from influenza infection such as pregnant women, young children, people with underlying disease and the elderly, along with occupational groups such a healthcare workers and farm workers. There are two main types of vaccines available: the parenteral inactivated influenza vaccine and the intranasal live attenuated influenza vaccine. The inactivated vaccines are licensed from 6 months of age and have been used for more than 50 years with a good safety profile. Inactivated vaccines are standardized according to the presence of the viral major surface glycoprotein hemagglutinin and protection is mediated by the induction of vaccine strain specific antibody responses. In contrast, the live attenuated vaccines are licensed in Europe for children from 2–17 years of age and provide a multifaceted immune response with local and systemic antibody and T cell responses but with no clear correlate of protection. Here we discuss the immunological immune responses elicited by the two vaccines and discuss future work to better define correlates of protection.
Borggren, Marie; Nielsen, Jens; Bragstad, Karoline
such as the induction of cellular and humoral immunity, inherent safety and rapid production time. We have previously developed a DNA vaccine encoding selected influenza proteins of pandemic origin and demonstrated broad protective immune responses in ferrets and pigs. In this study, we evaluated our DNA vaccine......The threat posed by the 2009 pandemic H1N1 virus emphasized the need for new influenza A virus vaccines inducing a broad cross-protective immune response for use in both humans and pigs. An effective and broad influenza vaccine for pigs would greatly benefit the pork industry and contribute...... to public health by diminishing the risk of emerging highly pathogenic reassortants. Current inactivated protein vaccines against swine influenza produce only short-lived immunity and have no efficacy against heterologous strains. DNA vaccines are a potential alternative with advantages...
Ruben, F L
Influenza is a modern day plague. In the young, the clinical picture is classical, but in the elderly, the disease may go unsuspected until complications such as pneumonia develop. Influenza A and B viruses are responsible, and these viruses mutate with great regularity. Antibodies to the HA and NA surface antigens of influenza viruses, both naturally and vaccine induced, are protective. The earliest influenza vaccines were crude, toxic, and ineffective. With modern purification techniques, the egg-grown viruses have been turned into safe, immunogenic, and effective killed-virus vaccines--whole virus and split virus. Surveillance permits the correct virus strains to be incorporated into each new vaccine. Those who have been experiencing the worst effects of influenza have been identified. These individuals need to be immunized each year. In the future, live influenza virus vaccines may offer the benefits of ease of administration and longer-lasting protection. Synthetic peptides, genetically engineered antigens, and even nonantigen (anti-idiotype) vaccines are possible, but such vaccines will require adjuvant enhancement. For the present, greater efforts must be made to use existing influenza vaccines.
This year, as usual, the Medical Service is helping to promote vaccination against seasonal influenza. Vaccination against seasonal flu is especially recommended for anyone who suffers from chronic pulmonary, cardio-vascular or kidney disease or diabetes, is recovering from a serious illness or major surgery, or is over 65 years of age. The flu virus is transmitted through the air and through contact with contaminated surfaces, so frequent hand-washing with soap and/or an antiseptic hand wash is of great importance. As soon as the first symptoms appear (fever above 38°, shivering, coughing, muscle and/or joint pains, generalised weakness), you are strongly recommended to stay at home to avoid spreading the virus. Anyone working on the CERN site who wishes to be vaccinated against seasonal flu should go to the Infirmary (Building 57, ground floor), with their dose of vaccine. The Medical Service will issue a prescription on the day of the vaccination for the purposes of reimbursement through UNIQA...
Full Text Available Annual outbreaks of influenza infections, caused by new influenza virus subtypes and high incidences of zoonosis, make seasonal influenza one of the most unpredictable and serious health threats worldwide. Currently available vaccines, though the main prevention strategy, can neither efficiently be adapted to new circulating virus subtypes nor provide high amounts to meet the global demand fast enough. New influenza vaccines quickly adapted to current virus strains are needed. In the present study we investigated the local toxicity and capacity of a new inhalable influenza vaccine to induce an antigen-specific recall response at the site of virus entry in human precision-cut lung slices (PCLS. This new vaccine combines recombinant H1N1 influenza hemagglutinin (HAC1, produced in tobacco plants, and a silica nanoparticle (NP-based drug delivery system. We found no local cellular toxicity of the vaccine within applicable concentrations. However higher concentrations of NP (≥10(3 µg/ml dose-dependently decreased viability of human PCLS. Furthermore NP, not the protein, provoked a dose-dependent induction of TNF-α and IL-1β, indicating adjuvant properties of silica. In contrast, we found an antigen-specific induction of the T cell proliferation and differentiation cytokine, IL-2, compared to baseline level (152±49 pg/mg vs. 22±5 pg/mg, which could not be seen for the NP alone. Additionally, treatment with 10 µg/ml HAC1 caused a 6-times higher secretion of IFN-γ compared to baseline (602±307 pg/mg vs. 97±51 pg/mg. This antigen-induced IFN-γ secretion was further boosted by the adjuvant effect of silica NP for the formulated vaccine to a 12-fold increase (97±51 pg/mg vs. 1226±535 pg/mg. Thus we were able to show that the plant-produced vaccine induced an adequate innate immune response and re-activated an established antigen-specific T cell response within a non-toxic range in human PCLS at the site of virus entry.
Tegenge, Million A; Mitkus, Robert J
Alpha (α)-tocopherol is a component of a new generation of squalene-containing oil-in-water (SQ/W) emulsion adjuvants that have been licensed for use in certain influenza vaccines. Since regulatory pharmacokinetic studies are not routinely required for influenza vaccines, the in vivo fate of this vaccine constituent is largely unknown. In this study, we constructed a physiologically based pharmacokinetic (PBPK) model for emulsified α-tocopherol in human adults and infants. An independent sheep PBPK model was also developed to inform the local preferential lymphatic transfer and for the purpose of model evaluation. The PBPK model predicts that α-tocopherol will be removed from the injection site within 24h and rapidly transfer predominantly into draining lymph nodes. A much lower concentration of α-tocopherol was estimated to peak in plasma within 8h. Any systemically absorbed α-tocopherol was predicted to accumulate slowly in adipose tissue, but not in other tissues. Model evaluation and uncertainty analyses indicated acceptable fit, with the fraction of dose taken up into the lymphatics as most influential on plasma concentration. In summary, this study estimates the in vivo fate of α-tocopherol in adjuvanted influenza vaccine, may be relevant in explaining its immunodynamics in humans, and informs current regulatory risk-benefit analyses. Published by Elsevier Inc.
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
Peiris, M; Yen, H-L
Influenza type A viruses affect humans and other animals and cause significant morbidity, mortality and economic impact. Influenza A viruses are well adapted to cross species barriers and evade host immunity. Viruses that cause no clinical signs in wild aquatic birds may adapt in domestic poultry to become highly pathogenic avian influenza viruses which decimate poultry flocks. Viruses that cause asymptomatic infection in poultry (e.g. the recently emerged A/H7N9 virus) may cause severe zoonotic disease and pose a major pandemic threat. Pandemic influenza arises at unpredictable intervals from animal viruses and, in its global spread, outpaces current technologies for making vaccines against such novel viruses. Confronting the threat of influenza in humans and other animals is an excellent example of a task that requires a One Health approach. Changes in travel, trade in livestock and pets, changes in animal husbandry practices, wet markets and complex marketing chains all contribute to an increased risk of the emergence of novel influenza viruses with the ability to cross species barriers, leading to epizootics or pandemics. Coordinated surveillance at the animal- human interface for pandemic preparedness, risk assessment, risk reduction and prevention at source requires coordinated action among practitioners in human and animal health and the environmental sciences. Implementation of One Health in the field can be challenging because of divergent short-term objectives. Successful implementation requires effort, mutual trust, respect and understanding to ensure that long-term goals are achieved without adverse impacts on agricultural production and food security.
Banzhoff, Angelika; Stoddard, Jeffrey J.
Seasonal influenza causes clinical illness and hospitalization in all age groups; however, conventional inactivated vaccines have only limited efficacy in young children. MF59®, an oil-in-water emulsion adjuvant, has been used since the 1990s to enhance the immunogenicity of influenza vaccines in the elderly, a population with waning immune function due to immunosenescence. Clinical trials now provide information to support a favorable immunogenicity and safety profile of MF59-adjuvanted influenza vaccine in young children. Published data indicate that Fluad®, a trivalent seasonal influenza vaccine with MF59, was immunogenic and well tolerated in young children, with a benefit/risk ratio that supports routine clinical use. A recent clinical trial also shows that Fluad provides high efficacy against PCR-confirmed influenza. Based on the results of clinical studies in children, the use of MF59-adjuvanted vaccine offers the potential to enhance efficacy and make vaccination a viable prevention and control strategy in this population. PMID:22327501
Hak, Eelko; Hoes, Arno W; Verheij, Theo J M
Influenza vaccination programmes should aim at reducing the burden from influenza among those who need it most. The primary aim of this literature review is to identify who should receive priority in influenza vaccination programmes. Risk factors for severe post-influenza complications include
Rowell, Janelle; Lo, Chia-Yun; Price, Graeme E; Misplon, Julia A; Epstein, Suzanne L; Garcia, Mayra
Universal influenza vaccines are designed to protect against diverse strains of influenza virus. Preclinical testing of new vaccine candidates is usually done in naïve animals, despite intended use in the human population with its varied immune history including responses to previous vaccinations. As an approach more relevant to human use, we tested a candidate universal influenza vaccine in mice with a history of conventional vaccination. Female BALB/c mice were given two intramuscular doses of inactivated influenza vaccine (IIV) or diphtheria and tetanus toxoids vaccine (DT), one month apart. Another group was given two intranasal doses of live attenuated influenza virus (LAIV). One month after the second dose, mice were given the universal influenza vaccine: recombinant adenoviruses expressing influenza A nucleoprotein (A/NP) and matrix 2 (M2) (A/NP + M2-rAd). Immune responses to universal vaccine antigens A/NP and M2 were assessed by ELISA and interferon-γ ELISPOT. Protection was tested by challenge with mouse-adapted A/FM/1/47 (H1N1) and monitoring for weight loss and survival. Universal vaccine performance was enhanced, inhibited or unaffected by particular prior vaccinations. Mice given Afluria IIV and LAIV had greater antibody and T-cell response to A/NP than mice without prior vaccination, providing examples of enhanced A/NP + M2-rAd performance. Though Fluvirin IIV partially inhibited, the universal vaccine still provided considerable protection unlike conventional vaccination. Fluzone IIV and DT had no effect on A/NP + M2-rAd performance. Thus our results demonstrate that universal vaccine candidate A/NP + M2-rAd was at least partially effective in mice with diverse prior histories. However, the degree of protection and nature of the immune responses may be affected by a history of conventional vaccination and suggests that performance in humans would be influenced by immune history. Published by Elsevier Ltd.
... DEPARTMENT OF HEALTH AND HUMAN SERVICES Office of the Secretary Pandemic Influenza Vaccines... potential to cause, sporadic human infections or have mutated to cause pandemics in humans; Whereas, these viruses may evolve into virus strains capable of causing a pandemic of human influenza because these...
Mullin, Jennifer; Ahmed, Muhammed S; Sharma, Ravi; Upile, Navdeep; Beer, Helen; Achar, Priya; Puksuriwong, Suttida; Ferrara, Francesca; Temperton, Nigel; McNamara, Paul; Lambe, Teresa; Gilbert, Sarah C; Zhang, Qibo
Recent efforts have been focused on the development of vaccines that could induce broad immunity against influenza virus, either through T cell responses to conserved internal antigens or B cell response to cross-reactive haemagglutinin (HA). We studied the capacity of Modified Vaccinia Ankara (MVA)-vectored influenza vaccines to induce cross-reactive immunity to influenza virus in human nasopharynx-associated lymphoid tissue (NALT) in vitro. Adenotonsillar cells were isolated and stimulated with MVA vaccines expressing either conserved nucleoprotein (NP) and matrix protein 1 (M1) (MVA-NP-M1) or pandemic H1N1 HA (MVA-pdmH1HA). The MVA vaccine uptake and expression, and T and B cell responses were analyzed. MVA-vectored vaccines were highly efficient infecting NALT and vaccine antigens were highly expressed by B cells. MVA-NP-M1 elicited T cell response with greater numbers of IFNγ-producing CD4+ T cells and tissue-resident memory T cells than controls. MVA-pdmH1HA induced cross-reactive anti-HA antibodies to a number of influenza subtypes, in an age-dependent manner. The cross-reactive antibodies include anti-avian H5N1 and mainly target HA2 domain. MVA vaccines are efficient in infecting NALT and the vaccine antigen is highly expressed by B cells. MVA vaccines expressing conserved influenza antigens induce cross-reactive T and B cell responses in human NALT in vitro, suggesting the potential as mucosal vaccines for broader immunity against influenza. Copyright © 2016 Elsevier Ltd. All rights reserved.
Anwar M. Hashem
Full Text Available 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.
Full Text Available BackgroundHuman milk is uniquely suited to provide optimal nutrition and immune protection to infants. Human milk oligosaccharides are structural complex and diverse consisting of short chain and long chain oligosaccharides typically present in a 9:1 ratio. 2′-Fucosyllactose (2′FL is one of the most prominent short chain oligosaccharides and is associated with anti-infective capacity of human milk.AimTo determine the effect of 2′FL on vaccination responsiveness (both innate and adaptive in a murine influenza vaccination model and elucidate mechanisms involved.MethodsA dose range of 0.25–5% (w/w dietary 2′FL was provided to 6-week-old female C57Bl/6JOlaHsd mice 2 weeks prior primary and booster vaccination until the end of the experiment. Intradermal (i.d. challenge was performed to measure the vaccine-specific delayed-type hypersensitivity (DTH. Antigen-specific antibody levels in serum as well as immune cell populations within several organs were evaluated using ELISA and flow cytometry, respectively. In an ex vivo restimulation assay, spleen cells were cocultured with influenza-loaded bone marrow-derived dendritic cells (BMDCs to study the effects of 2′FL on vaccine-specific CD4+ and CD8+ T-cell proliferation and cytokine secretions. Furthermore, the direct immune regulatory effects of 2′FL were confirmed using in vitro BMDCs T-cell cocultures.ResultsDietary 2′FL significantly (p < 0.05 enhanced vaccine specific DTH responses accompanied by increased serum levels of vaccine-specific immunoglobulin (Ig G1 and IgG2a in a dose-dependent manner. Consistently, increased activation marker (CD27 expression on splenic B-cells was detected in mice receiving 2′FL as compared to control mice. Moreover, proliferation of vaccine-specific CD4+ and CD8+ T-cells, as well as interferon-γ production after ex vivo restimulation were significantly increased in spleen cells of mice receiving 2′FL as compared to control mice, which were
... Exclusive License: Veterinary Biological Products for Swine Influenza Vaccines AGENCY: National Institutes....7. The invention relates to compositions and methods of use as Veterinary Influenza Vaccines... to humans. This technology describes DNA vaccines against influenza serotypes H5N1, H1N1, H3N2, and...
Full Text Available Previous modeling studies have identified the vaccination coverage level necessary for preventing influenza epidemics, but have not shown whether this critical coverage can be reached. Here we use computational modeling to determine, for the first time, whether the critical coverage for influenza can be achieved by voluntary vaccination. We construct a novel individual-level model of human cognition and behavior; individuals are characterized by two biological attributes (memory and adaptability that they use when making vaccination decisions. We couple this model with a population-level model of influenza that includes vaccination dynamics. The coupled models allow individual-level decisions to influence influenza epidemiology and, conversely, influenza epidemiology to influence individual-level decisions. By including the effects of adaptive decision-making within an epidemic model, we can reproduce two essential characteristics of influenza epidemiology: annual variation in epidemic severity and sporadic occurrence of severe epidemics. We suggest that individual-level adaptive decision-making may be an important (previously overlooked causal factor in driving influenza epidemiology. We find that severe epidemics cannot be prevented unless vaccination programs offer incentives. Frequency of severe epidemics could be reduced if programs provide, as an incentive to be vaccinated, several years of free vaccines to individuals who pay for one year of vaccination. Magnitude of epidemic amelioration will be determined by the number of years of free vaccination, an individuals' adaptability in decision-making, and their memory. This type of incentive program could control epidemics if individuals are very adaptable and have long-term memories. However, incentive-based programs that provide free vaccination for families could increase the frequency of severe epidemics. We conclude that incentive-based vaccination programs are necessary to control
Crovari, P; Alberti, M; Alicino, C
Since the isolation of influenza virus in 1933, a great deal of work was carried out in order to develop influenza vaccines and improve these fundamental tools of prevention in terms of production, quality control, safety and tolerability, and immunogenicity. The paper summarizes the cornerstones of the continuous evolution of influenza vaccines and the most recent and promising developments in this field.
... 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: ...
Gordon, David L; Sajkov, Dimitar; Honda-Okubo, Yoshikazu; Wilks, Samuel H; Aban, Malet; Barr, Ian G; Petrovsky, Nikolai
Influenza vaccines are usually non-adjuvanted but addition of adjuvant may improve immunogenicity and permit dose-sparing, critical for vaccine supply in the event of an influenza pandemic. The aim of this first-in-man study was to determine the effect of delta inulin adjuvant on the safety and immunogenicity of a reduced dose seasonal influenza vaccine. Healthy male and female adults aged 18-65years were recruited to participate in a randomized controlled study to compare the safety, tolerability and immunogenicity of a reduced-dose 2007 Southern Hemisphere trivalent inactivated influenza vaccine formulated with Advax™ delta inulin adjuvant (LTIV+Adj) when compared to a full-dose of the standard TIV vaccine which does not contain an adjuvant. LTIV+Adj provided equivalent immunogenicity to standard TIV vaccine as assessed by hemagglutination inhibition (HI) assays against each vaccine strain as well as against a number of heterosubtypic strains. HI responses were sustained at 3months post-immunisation in both groups. Antibody landscapes against a large panel of H3N2 influenza viruses showed distinct age effects whereby subjects over 40years old had a bimodal baseline HI distribution pattern, with the highest HI titers against the very oldest H3N2 isolates and with a second HI peak against influenza isolates from the last 5-10years. By contrast, subjects >40years had a unimodal baseline HI distribution with peak recognition of H3N2 isolates from approximately 20years ago. The reduced dose TIV vaccine containing Advax adjuvant was well tolerated and no safety issues were identified. Hence, delta inulin may be a useful adjuvant for use in seasonal or pandemic influenza vaccines. Australia New Zealand Clinical Trial Registry: ACTRN12607000599471. Copyright © 2016 Elsevier Ltd. All rights reserved.
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…
Benne, CA; Harmsen, M; Tavares, L; Kraaijeveld, CA; De Jong, JC
A neutralization enzyme immunoassay (N-EIA) was used to determine the neutralizing serum antibody titers to influenza A/Taiwan/1/86 (H1N1) and Beijing/353/89 (H3N2) viruses after vaccination of 51 human immunodeficiency virus (HIV) type 1-infected individuals and 10 healthy noninfected controls
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.
Treanor, John; Nolan, Carrie; O'Brien, Diane; Burt, David; Lowell, George; Linden, Janine; Fries, Louis
Two randomized, blinded, active comparator-controlled trials of a prototype monovalent A/Beijing/262/95 (H1N1) - proteosome vaccine delivered by intranasal spray were performed in healthy adults. Overall, the intranasal proteosome-adjuvanted vaccine was well-tolerated with only mild stuffy nose and rhinorrhea seen more frequently in recipients of vaccine than in recipients of intranasal saline, and there were no serious adverse events. The intranasal proteosome-adjuvanted vaccine induced serum hemagglutination inhibiting (HAI) and nasal secretory IgA (sIgA) responses specific for the influenza antigen. Serum HAI responses were most influenced by the dosage level, whereas mucosal sIgA responses, although demonstrable with both single-dose and two-dose vaccine regimens, appeared to be greater in response to two-dose regimens (regardless of dose level). Further evaluation of mucosal influenza immunization using the proteosome adjuvant/delivery system is clearly warranted.
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),...
Assi, Tina-Marie; Rookkapan, Korngamon; Rajgopal, Jayant; Sornsrivichai, Vorasith; Brown, Shawn T; Welling, Joel S; Norman, Bryan A; Connor, Diana L; Chen, Sheng-I; Slayton, Rachel B; Laosiritaworn, Yongjua; Wateska, Angela R; Wisniewski, Stephen R; Lee, Bruce Y
When policymakers make decision about the target populations and timing of influenza vaccination, they may not consider the impact on the vaccine supply chains, which may in turn affect vaccine availability. Our goal is to explore the effects on the Thailand vaccine supply chain of introducing influenza vaccines and varying the target populations and immunization time-frames. We Utilized our custom-designed software HERMES (Highly Extensible Resource for Modeling Supply Chains), we developed a detailed, computational discrete-event simulation model of the Thailand's National Immunization Program (NIP) supply chain in Trang Province, Thailand. A suite of experiments simulated introducing influenza vaccines for different target populations and over different time-frames prior to and during the annual influenza season. Introducing influenza vaccines creates bottlenecks that reduce the availability of both influenza vaccines as well as the other NIP vaccines, with provincial to district transport capacity being the primary constraint. Even covering only 25% of the Advisory Committee on Immunization Practice-recommended population while administering the vaccine over six months hinders overall vaccine availability so that only 62% of arriving patients can receive vaccines. Increasing the target population from 25% to 100% progressively worsens these bottlenecks, while increasing influenza vaccination time-frame from 1 to 6 months decreases these bottlenecks. Since the choice of target populations for influenza vaccination and the time-frame to deliver this vaccine can substantially affect the flow of all vaccines, policy-makers may want to consider supply chain effects when choosing target populations for a vaccine. Copyright © 2012 Elsevier Ltd. All rights reserved.
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. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.
Trombetta, Claudia Maria; Gianchecchi, Elena; Montomoli, Emanuele
ABSTRACT The safety of vaccines is a critical factor in maintaining public trust in national vaccination programs. Vaccines are recommended for children, adults and elderly subjects and have to meet higher safety standards, since they are administered to healthy subjects, mainly healthy children. Although vaccines are strictly monitored before authorization, the possibility of adverse events and/or rare adverse events cannot be totally eliminated. Two main types of influenza vaccines are currently available: parenteral inactivated influenza vaccines and intranasal live attenuated vaccines. Both display a good safety profile in adults and children. However, they can cause adverse events and/or rare adverse events, some of which are more prevalent in children, while others with a higher prevalence in adults. The aim of this review is to provide an overview of influenza vaccine safety according to target groups, vaccine types and production methods. PMID:29297746
Vaccination is the most effective strategy to prevent influenza. It is recommended that influenza vaccine be administered each year before the influenza season, i.e. from March to June, although for individuals at increased risk of severe influenza in whom vaccination was missed, vaccine may be administered later.
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. Copyright © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Clar,Christine; Oseni,Zainab; Flowers,Nadine; Keshtkar-Jahromi,Maryam; Rees,Karen
ABSTRACTBACKGROUND: This is an update of the original review published in 2008. The risk of adverse cardiovascular outcomes is increased with influenza-like infection, and vaccination against influenza may improve cardiovascular outcomes.OBJECTIVES: To assess the potential benefits of influenza vaccination for primary and secondary prevention of cardiovascular disease.METHODS:Search methods:We searched the following electronic databases on 18 October 2013: The Cochrane Library (including Coch...
Thacker, Eileen; Janke, Bruce
Influenza viruses are able to infect humans, swine, and avian species, and swine have long been considered a potential source of new influenza viruses that can infect humans. Swine have receptors to which both avian and mammalian influenza viruses bind, which increases the potential for viruses to exchange genetic sequences and produce new reassortant viruses in swine. A number of genetically diverse viruses are circulating in swine herds throughout the world and are a major cause of concern to the swine industry. Control of swine influenza is primarily through the vaccination of sows, to protect young pigs through maternally derived antibodies. However, influenza viruses continue to circulate in pigs after the decay of maternal antibodies, providing a continuing source of virus on a herd basis. Measures to control avian influenza in commercial poultry operations are dictated by the virulence of the virus. Detection of a highly pathogenic avian influenza (HPAI) virus results in immediate elimination of the flock. Low-pathogenic avian influenza viruses are controlled through vaccination, which is done primarily in turkey flocks. Maintenance of the current HPAI virus-free status of poultry in the United States is through constant surveillance of poultry flocks. Although current influenza vaccines for poultry and swine are inactivated and adjuvanted, ongoing research into the development of newer vaccines, such as DNA, live-virus, or vectored vaccines, is being done. Control of influenza virus infection in poultry and swine is critical to the reduction of potential cross-species adaptation and spread of influenza viruses, which will minimize the risk of animals being the source of the next pandemic.
Kang, Sang-Moo; Song, Jae-Min; Kim, Yeu-Chun
In recent years with the threat of pandemic influenza and other public health needs, alternative vaccination methods other than intramuscular immunization have received great attention. The skin and mucosal surfaces are attractive sites probably because of both non-invasive access to the vaccine delivery and unique immunological responses. Intradermal vaccines using a microinjection system (BD Soluvia) and intranasal vaccines (FluMist) are licensed. As a new vaccination method, solid microneedles have been developed using a simple device that may be suitable for self-administration. Because coated micorneedle influenza vaccines are administered in the solid state, developing formulations maintaining the stability of influenza vaccines is an important issue to be considered. Marketable microneedle devices and clinical trials remain to be developed. Other alternative mucosal routes such as oral and intranasal delivery systems are also attractive for inducing cross protective mucosal immunity but effective non-live mucosal vaccines remain to be developed. PMID:22697052
Carlos J Montoya
Full Text Available Given that highly active antiretroviral therapy (HAART has been demonstrated useful to restore immune competence in type-1 human immunodeficiency virus (HIV-1-infected subjects, we evaluated the specific antibody response to influenza vaccine in a cohort of HIV-1-infected children on HAART so as to analyze the quality of this immune response in patients under antiretroviral therapy. Sixteen HIV-1-infected children and 10 HIV-1 seronegative controls were immunized with a commercially available trivalent inactivated influenza vaccine containing the strains A/H1N1, A/H3N2, and B. Serum hemagglutinin inhibition (HI antibody titers were determined for the three viral strains at the time of vaccination and 1 month later. Immunization induced a significantly increased humoral response against the three influenza virus strains in controls, and only against A/H3N2 in HIV-1-infected children. The comparison of post-vaccination HI titers between HIV-1+ patients and HIV-1 negative controls showed significantly higher HI titers against the three strains in controls. In addition, post vaccination protective HI titers (defined as equal to or higher than 1:40 against the strains A/H3N2 and B were observed in a lower proportion of HIV-1+ children than in controls, while a similar proportion of individuals from each group achieved protective HI titers against the A/H1N1 strain. The CD4+ T cell count, CD4/CD8 T cells ratio, and serum viral load were not affected by influenza virus vaccination when pre- vs post-vaccination values were compared. These findings suggest that despite the fact that HAART is efficient in controlling HIV-1 replication and in increasing CD4+ T cell count in HIV-1-infected children, restoration of immune competence and response to cognate antigens remain incomplete, indicating that additional therapeutic strategies are required to achieve a full reconstitution of immune functions.
Apenteng, Bettye A; Opoku, Samuel T
The organizational literature on infection control in residential care facilities is limited. Using a nationally representative dataset, we examined the organizational factors associated with implementing at least 1 influenza-related employee vaccination policy/program, as well as the effect of vaccination policies on health care worker (HCW) influenza vaccine uptake in residential care facilities. The study was a cross-sectional study using data from the 2010 National Survey of Residential Care Facilities. Multivariate logistic regression analysis was used to address the study's objectives. Facility size, director's educational attainment, and having a written influenza pandemic preparedness plan were significantly associated with the implementation of at least 1 influenza-related employee vaccination policy/program, after controlling for other facility-level factors. Recommending vaccination to employees, providing vaccination on site, providing vaccinations to employees at no cost, and requiring vaccination as a condition of employment were associated with higher employee influenza vaccination rates. Residential care facilities can improve vaccination rates among employees by adopting effective employee vaccination policies. Copyright © 2014 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.
Hirzel, Cédric; Kumar, Deepali
The aim of this study was to highlight recent evidence on important aspects of influenza vaccination in solid organ transplant recipients. Influenza vaccine is the most evaluated vaccine in transplant recipients. The immunogenicity of the vaccine is suboptimal after transplantation. Newer formulations such as inactivated unadjuvanted high-dose influenza vaccine and the administration of a booster dose within the same season have shown to increase response rates. Intradermal vaccination and adjuvanted vaccines did not show clear benefit over standard influenza vaccines. Recent studies in transplant recipients do not suggest a higher risk for allograft rejection, neither after vaccination with a standard influenza vaccine nor after the administration of nonstandard formulation (high-dose, adjuvanted vaccines), routes (intradermally) or a booster dose. Nevertheless, influenza vaccine coverage in transplant recipients is still unsatisfactory low, potentially due to misinterpretation of risks and benefits. Annual influenza vaccination is well tolerated and is an important part of long-term care of solid organ transplant recipients.
virus. The three types of human influenza viruses are H1N1, H1N2 , and H3N2. Influenza type A viruses are constantly changing and this requires...ORDERING AND DISTRIBUTION OF THE INFLUENZA VACCINE by James Richard Gurr June 2006 Thesis Advisor: Walter Owen Second Reader: Moshe...Ordering and Distribution of the Influenza Vaccine 6. AUTHOR(S) James Richard Gurr 5. FUNDING NUMBERS 7. PERFORMING ORGANIZATION NAME(S) AND
Amorij, J-P; Huckriede, A; Wilschut, J; Frijlink, H W; Hinrichs, W L J
Influenza vaccination represents the cornerstone of influenza prevention. However, today all influenza vaccines are formulated as liquids that are unstable at ambient temperatures and have to be stored and distributed under refrigeration. In order to stabilize influenza vaccines, they can be brought
Full Text Available Influenza is one of the most common respiratory diseases affecting people of all age groups all over the world. Seasonal influenza leads to substantial morbidity and mortality on a global scale. Vaccines are undeniably one of the most important health advances of the past century, however, managing influenza in working populations remains a difficult issue. Vaccination of health care workers (HCW is an efficient way to reduce the risk of occupational infection and to prevent nosocomial transmission to vulnerable patients. Despite this, achieving high immunization rates among those professionals is a challenge. Knowledge and attitudes of healthcare providers have significant impact on the frequency with which vaccines are offered and accepted, but many HCWs are poorly equipped to make informed recommendations about vaccine merits and risks. Principal reasons for vaccination are the willing not to be infected and avoiding transmission to patients and the family. The main reasons for refusing is lack of time, a feeling of invulnerability to vaccination, conviction of not being at risk, of being too young or in good health. Misconceptions about influenza vaccine efficacy, like adverse effects, and fear of contracting illness from the vaccine are significantly associated with noncompliance with vaccination. Therefore, strategies to increase awareness of the importance of recommending influenza immunization among health professionals are required. Med Pr 2013;64(1:119–129
Full Text Available 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
Lehmann, Birthe A; Ruiter, Robert A C; Wicker, Sabine; Chapman, Gretchen; Kok, Gerjo
Influenza vaccination is recommended for all healthcare personnel (HCP) and most institutions offer vaccination for free and on site. However, medical students do not always have such easy access, and the predictors that might guide the motivation of medical students to get vaccinated are largely unknown. We conducted a cross-sectional survey study among pre-clinical medical students in a German University hospital to assess the social cognitive predictors of influenza vaccination, as well as reasons for refusal and acceptance of the vaccine. Findings show that pre-clinical medical students have comparable knowledge gaps and negative attitudes towards influenza vaccination that have previously been reported among HCP. Lower injunctive norms and higher feelings of autonomy contribute to no intention to get vaccinated against influenza, while a positive instrumental attitude and higher feelings of autonomy contribute to a high intention to get vaccinated. The variables in the regression model explained 20% of the variance in intention to get vaccinated. The identified factors should be addressed early in medical education, and hospitals might benefit from a more inclusive vaccination program and accessibility of free vaccines for their medical students.
Thi H. O. Nguyen
Full Text Available Influenza A virus (IAVs infections impact significantly on global health, being particularly problematic in children, the elderly, pregnant women, indigenous populations and people with co-morbidities. Antibody-based vaccines require annual administration to combat rapidly acquired mutations modifying the surface haemagglutinin (HA and neuraminidase (NA glycoproteins. Conversely, influenza-specific CD8+ T cell responses directed at peptides derived from the more conserved internal virus proteins are known to be protective, suggesting that T cell-based vaccines may provide long-lasting cross-protection. This review outlines the importance of CD8+ T cell immunity to seasonal influenza and pandemic IAVs and summarises current vaccination strategies for inducing durable CD8+ T cell memory. Aspects of future IAV vaccine design and the use of live virus challenge in humans to establish proof of principle are also discussed.
Annual vaccination is since many years the corner stone of Influenza control strategy. Because conventional vaccine are needle-based, are less immunogenic in old people and induce only systemic IgG production, intranasal and intradermal vaccines that are recently or will be soon available in Belgium will offer distinct advantages. Intradermal vaccination is on the Belgian market since 2010. A stronger immune response that allows an antigen sparing strategy is elicited because antigens are delivered near the dermal dendritic cells. Local side effects are more pronounced than after intramuscular injection. The needle-free intranasal vaccine that has been approved for use in people less than 18 years old by the EMEA in October 2010 induces also a mucosal IgA response. Improved clinical results than with intramuscular vaccine has been documented in several studies in children. Several conditions are contraindication to nasal vaccination because of patterns of side effects and because the vaccine is an live-attenuated vaccine. Pregnant women has become a top priority for Influenza vaccination in the recommendations of the High Council of Health in Belgium since the 2009 H1N1 pandemic. Several studies has since then documented the increased risk for Influenza-related morbidity in pregnant women especially during the third trimester and independently of the presence of other comorbidities. Reduced incidence of documented Influenza and of Influenza-related hospitalizations are observed in the new born of vaccinated women until 6 months of age. Availability of new vaccines for Influenza and better knowledge of the benefit of vaccination in target populations are important tools to optimize vaccine coverage of the population.
An Intranasal Proteosome-Adjuvanted Trivalent Influenza Vaccine Is Safe, Immunogenic & Efficacious in the Human Viral Influenza Challenge Model. Serum IgG & Mucosal IgA Are Important Correlates of Protection against Illness Associated with Infection.
Full Text Available A Proteosome-adjuvanted trivalent inactivated influenza vaccine (P-TIV administered intra-nasally was shown to be safe, well tolerated and immunogenic in both systemic and mucosal compartments, and effective at preventing illness associated with evidence of influenza infection.In two separate studies using the human viral challenge model, subjects were selected to be immunologically naive to A/Panama/2007/1999 (H3N2 virus and then dosed via nasal spray with one of three regimens of P-TIV or placebo. One or two doses, 15 μg or 30 μg, were given either once only or twice 14 days apart (1 x 30 μg, 2 x 30 μg, 2 x 15 μg and subjects were challenged with A/Panama/2007/1999 (H3N2 virus. Immune responses to the vaccine antigens were measured by haemagglutination inhibition assay (HAI and nasal wash secretory IgA (sIgA antibodies.Vaccine reactogenicity was mild, predictable and generally consistent with earlier Phase I studies with this vaccine. Seroconversion to A/Panama/2007/1999 (H3N2, following vaccination but prior to challenge, occurred in 57% to 77% of subjects in active dosing groups and 2% of placebo subjects. The greatest relative rise in sIgA, following vaccination but prior to challenge, was observed in groups that received 2 doses.Intranasal vaccination significantly protected against influenza (as defined by influenza symptoms combined with A/Panama seroconversion following challenge with A/Panama/2007/1999 (H3N2. When data were pooled from both studies, efficacy ranged from 58% to 82% in active dosing groups for any influenza symptoms with seroconversion, 67% to 85% for systemic or lower respiratory illness and seroconversion, and 65% to 100% for febrile illness and seroconversion. The two dose regimen was found to be superior to the single dose regimen. In this study, protection against illness associated with evidence of influenza infection (evidence determined by seroconversion following challenge with virus, significantly
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.
Full Text Available Influenza virus infections are a significant cause of morbidity and mortality in the human population. Depending on the virulence of the influenza virus strain, as well as the immunological status of the infected individual, the severity of the respiratory disease may range from sub-clinical or mild symptoms to severe pneumonia that can sometimes lead to death. Vaccines remain the primary public health measure in reducing the influenza burden. Though the first influenza vaccine preparation was licensed more than 60 years ago, current research efforts seek to develop novel vaccination strategies with improved immunogenicity, effectiveness, and breadth of protection. Animal models of influenza have been essential in facilitating studies aimed at understanding viral factors that affect pathogenesis and contribute to disease or transmission. Among others, mice, ferrets, pigs, and nonhuman primates have been used to study influenza virus infection in vivo, as well as to do pre-clinical testing of novel vaccine approaches. Here we discuss and compare the unique advantages and limitations of each model.
Jang, Yo Han
Despite recent innovative advances in molecular virology and the developments of vaccines, influenza virus remains a serious burden for human health. Vaccination has been considered a primary countermeasure for prevention of influenza infection. Live attenuated influenza vaccines (LAIVs) are particularly attracting attention as an effective strategy due to several advantages over inactivated vaccines. Cold-adaptation, as a classical means for attenuating viral virulence, has been successfully used for generating safe and effective donor strains of LAIVs against seasonal epidemics and occasional pandemics. Recently, the advent of reverse genetics technique expedited a variety of rational strategies to broaden the pool of LAIVs. Considering the breadth of antigenic diversity of influenza virus, the pool of LAIVs is likely to equip us with better options for controlling influenza pandemics. With a brief reflection on classical attenuating strategies used at the initial stage of development of LAIVs, especially on the principles underlying the development of cold-adapted LAIVs, we further discuss and outline other attenuation strategies especially with respect to the rationales for attenuation, and their practicality for mass production. Finally, we propose important considerations for a rational vaccine design, which will provide us with practical guidelines for improving the safety and effectiveness of LAIVs. PMID:23596576
Full Text Available 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.
Full Text Available Vaccination remains the principal way to control seasonal infections and is the most effective method of reducing influenza-associated morbidity and mortality. Since the 1940s, the main method of producing influenza vaccines has been an egg-based production process. However, in the event of a pandemic, this method has a significant limitation, as the time lag from strain isolation to final dose formulation and validation is six months. Indeed, production in eggs is a relatively slow process and production yields are both unpredictable and highly variable from strain to strain. In particular, if the next influenza pandemic were to arise from an avian influenza virus, and thus reduce the egg-laying hen population, there would be a shortage of embryonated eggs available for vaccine manufacturing. Although the production of egg-derived vaccines will continue, new technological developments have generated a cell-culture-based influenza vaccine and other more recent platforms, such as synthetic influenza vaccines.
Full Text Available 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.
Influenza is caused by a highly infectious RNA virus, which usually occurs in a seasonal pattern with epidemics in the winter months. The objective of this study was to determine the uptake of the influenza vaccine in a pregnant population and ascertain the reasons why some women did not receive it. A prospective cohort study was conducted over a two-week period in January 2016 in the National Maternity Hospital Dublin, a tertiary referral maternity hospital delivering over 9000 infants per year. There were 504 women studied over the 2-week period. Overall, 197(39.1%) women received the vaccine at a mean gestational age 20.9 weeks (SD 7.0). Given the increased rates of influenza in the community and the associated implications for mother and infant, it is important that pregnant women are educated regarding the risks of influenza in pregnancy and encourage this cohort to be vaccinated.
Graves, Meredith C; Harris, Jeffrey R; Hannon, Peggy A; Hammerback, Kristen; Parrish, Amanda T; Ahmed, Faruque; Zhou, Chuan; Allen, Claire L
To evaluate an evidence-based workplace approach to increasing adult influenza vaccination levels applied in the restaurant setting We implemented an intervention and conducted a pre/post analysis to determine effect on vaccination. Eleven Seattle-area restaurants. Restaurants with 25+ employees speaking English or Spanish and over 18 years. Restaurants received influenza vaccination promotion materials, assistance arranging on-site vaccination events, and free influenza vaccinations for employees. Pre/post employee surveys of vaccination status with direct observation and employer interviews to evaluate implementation. We conducted descriptive analysis of employee survey data and performed qualitative analysis of implementation data. To assess intervention effect, we used a mixed-effects logistic regression model with a restaurant-specific random effect. Vaccination levels increased from 26% to 46% (adjusted odds ratio 2.33, 95% confidence interval 1.69, 3.22), with 428 employees surveyed preintervention, 305 surveyed postintervention, and response rates of 73% and 55%, respectively. The intervention was effective across subgroups, but there were restaurant-level differences. An access-based workplace intervention can increase influenza vaccination levels in restaurant employees, but restaurant-level factors may influence success. © 2016 by American Journal of Health Promotion, Inc.
Groenwold, R. H. H.; Hoes, A. W.; Hak, E.
Estimates of influenza vaccine effectiveness have mostly been derived from nonrandomised studies and therefore are potentially confounded. The aim of the current study was to estimate influenza vaccine effectiveness in preventing mortality among the elderly, taking both measured and unmeasured
O'Donnell, Christopher D; Wright, Amber; Vogel, Leatrice; Boonnak, Kobporn; Treanor, John J; Subbarao, Kanta
The hypothesis of original antigenic sin (OAS) states that the imprint established by an individual's first influenza virus infection governs the antibody response thereafter. Subsequent influenza virus infection results in an antibody response against the original infecting virus and an impaired immune response against the newer influenza virus. The purpose of our study was to seek evidence of OAS after infection or vaccination with the 2009 pandemic H1N1 (2009 pH1N1) virus in ferrets and humans previously infected with H1N1 viruses with various antigenic distances from the 2009 pH1N1 virus, including viruses from 1935 through 1999. In ferrets, seasonal H1N1 priming did not diminish the antibody response to infection or vaccination with the 2009 pH1N1 virus, nor did it diminish the T-cell response, indicating the absence of OAS in seasonal H1N1 virus-primed ferrets. Analysis of paired samples of human serum taken before and after vaccination with a monovalent inactivated 2009 pH1N1 vaccine showed a significantly greater-fold rise in the titer of antibody against the 2009 pH1N1 virus than against H1N1 viruses that circulated during the childhood of each subject. Thus, prior experience with H1N1 viruses did not result in an impairment of the antibody response against the 2009 pH1N1 vaccine. Our data from ferrets and humans suggest that prior exposure to H1N1 viruses did not impair the immune response against the 2009 pH1N1 virus.
Stratton, Kathleen R
..., unlike other vaccines. The Immunization Safety Review committee reviewed the data on influenza vaccine and neurological conditions and concluded that the evidence favored rejection of a causal relationship...
Boonsathorn, Naphatsawan; Panthong, Sumolrat; Koksunan, Sarawut; Chittaganpitch, Malinee; Phuygun, Siripaporn; Waicharoen, Sunthareeya; Prachasupap, Apichai; Sasaki, Tadahiro; Kubota-Koketsu, Ritsuko; Yasugi, Mayo; Ono, Ken-ichiro; Arai, Yasuha
Highlights: • A human monoclonal antibody against influenza virus was produced from a volunteer. • The antibody was generated from the PBMCs of the volunteer using the fusion method. • The antibody neutralized heterosubtypically group 1 influenza A viruses (H1 and H9). • The antibody targeted a novel epitope in globular head region of the hemagglutinin. • Sequences of the identified epitope are highly conserved among H1 and H9 subtypes. - Abstract: Most neutralizing antibodies elicited during influenza virus infection or by vaccination have a narrow spectrum because they usually target variable epitopes in the globular head region of hemagglutinin (HA). In this study, we describe a human monoclonal antibody (HuMAb), 5D7, that was prepared from the peripheral blood lymphocytes of a vaccinated volunteer using the fusion method. The HuMAb heterosubtypically neutralizes group 1 influenza A viruses, including seasonal H1N1, 2009 pandemic H1N1 (H1N1pdm) and avian H9N2, with a strong hemagglutinin inhibition activity. Selection of an escape mutant showed that the HuMAb targets a novel conformational epitope that is located in the HA head region but is distinct from the receptor binding site. Furthermore, Phe114Ile substitution in the epitope made the HA unrecognizable by the HuMAb. Amino acid residues in the predicted epitope region are also highly conserved in the HAs of H1N1 and H9N2. The HuMAb reported here may be a potential candidate for the development of therapeutic/prophylactic antibodies against H1 and H9 influenza viruses
Boonsathorn, Naphatsawan; Panthong, Sumolrat [Medical Life Sciences Institute, Department of Medical Sciences, Ministry of Public Health, Muang, Nonthaburi (Thailand); Japan Science and Technology Agency/Japan International Cooperation Agency, Science and Technology Research Partnership for Sustainable Development (JST/JICA, SATREPS), Tokyo (Japan); Koksunan, Sarawut [Medical Life Sciences Institute, Department of Medical Sciences, Ministry of Public Health, Muang, Nonthaburi (Thailand); Chittaganpitch, Malinee; Phuygun, Siripaporn; Waicharoen, Sunthareeya [National Institute of Health, Department of Medical Sciences, Ministry of Public Health, Muang, Nonthaburi (Thailand); Prachasupap, Apichai [Medical Life Sciences Institute, Department of Medical Sciences, Ministry of Public Health, Muang, Nonthaburi (Thailand); Japan Science and Technology Agency/Japan International Cooperation Agency, Science and Technology Research Partnership for Sustainable Development (JST/JICA, SATREPS), Tokyo (Japan); Sasaki, Tadahiro [Department of Virology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka (Japan); Japan Science and Technology Agency/Japan International Cooperation Agency, Science and Technology Research Partnership for Sustainable Development (JST/JICA, SATREPS), Tokyo (Japan); Kubota-Koketsu, Ritsuko [Kanonji Institute, The Research Foundation for Microbial Diseases of Osaka University, Kanonji, Kagawa (Japan); Yasugi, Mayo [Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Izumisano, Osaka (Japan); Ono, Ken-ichiro [Ina Laboratory, Medical and Biological Laboratories Corporation, Ltd., Ina, Nagano (Japan); Japan Science and Technology Agency/Japan International Cooperation Agency, Science and Technology Research Partnership for Sustainable Development (JST/JICA, SATREPS), Tokyo (Japan); Arai, Yasuha [Department of Virology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka (Japan); and others
Highlights: • A human monoclonal antibody against influenza virus was produced from a volunteer. • The antibody was generated from the PBMCs of the volunteer using the fusion method. • The antibody neutralized heterosubtypically group 1 influenza A viruses (H1 and H9). • The antibody targeted a novel epitope in globular head region of the hemagglutinin. • Sequences of the identified epitope are highly conserved among H1 and H9 subtypes. - Abstract: Most neutralizing antibodies elicited during influenza virus infection or by vaccination have a narrow spectrum because they usually target variable epitopes in the globular head region of hemagglutinin (HA). In this study, we describe a human monoclonal antibody (HuMAb), 5D7, that was prepared from the peripheral blood lymphocytes of a vaccinated volunteer using the fusion method. The HuMAb heterosubtypically neutralizes group 1 influenza A viruses, including seasonal H1N1, 2009 pandemic H1N1 (H1N1pdm) and avian H9N2, with a strong hemagglutinin inhibition activity. Selection of an escape mutant showed that the HuMAb targets a novel conformational epitope that is located in the HA head region but is distinct from the receptor binding site. Furthermore, Phe114Ile substitution in the epitope made the HA unrecognizable by the HuMAb. Amino acid residues in the predicted epitope region are also highly conserved in the HAs of H1N1 and H9N2. The HuMAb reported here may be a potential candidate for the development of therapeutic/prophylactic antibodies against H1 and H9 influenza viruses.
Mooney, Alaina J; Gabbard, Jon D; Li, Zhuo; Dlugolenski, Daniel A; Johnson, Scott K; Tripp, Ralph A; He, Biao; Tompkins, S Mark
Seasonal human influenza virus continues to cause morbidity and mortality annually, and highly pathogenic avian influenza (HPAI) viruses along with other emerging influenza viruses continue to pose pandemic threats. Vaccination is considered the most effective measure for controlling influenza; however, current strategies rely on a precise vaccine match with currently circulating virus strains for efficacy, requiring constant surveillance and regular development of matched vaccines. Current vaccines focus on eliciting specific antibody responses against the hemagglutinin (HA) surface glycoprotein; however, the diversity of HAs across species and antigenic drift of circulating strains enable the evasion of virus-inhibiting antibody responses, resulting in vaccine failure. The neuraminidase (NA) surface glycoprotein, while diverse, has a conserved enzymatic site and presents an appealing target for priming broadly effective antibody responses. Here we show that vaccination with parainfluenza virus 5 (PIV5), a promising live viral vector expressing NA from avian (H5N1) or pandemic (H1N1) influenza virus, elicited NA-specific antibody and T cell responses, which conferred protection against homologous and heterologous influenza virus challenges. Vaccination with PIV5-N1 NA provided cross-protection against challenge with a heterosubtypic (H3N2) virus. Experiments using antibody transfer indicate that antibodies to NA have an important role in protection. These findings indicate that PIV5 expressing NA may be effective as a broadly protective vaccine against seasonal influenza and emerging pandemic threats. IMPORTANCE Seasonal influenza viruses cause considerable morbidity and mortality annually, while emerging viruses pose potential pandemic threats. Currently licensed influenza virus vaccines rely on the antigenic match of hemagglutinin (HA) for vaccine strain selection, and most vaccines rely on HA inhibition titers to determine efficacy, despite the growing
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…
Full Text Available Despite advancements in immunotherapeutic approaches, influenza continues to cause severe illness, particularly among immunocompromised individuals, young children, and elderly adults. Vaccination is the most effective way to reduce rates of morbidity and mortality caused by influenza viruses. Frequent genetic shift and drift among influenza-virus strains with the resultant disparity between circulating and vaccine virus strains limits the effectiveness of the available conventional influenza vaccines. One approach to overcome this limitation is to develop a universal influenza vaccine that could provide protection against all subtypes of influenza viruses. Moreover, the development of a novel or improved universal influenza vaccines may be greatly facilitated by new technologies including virus-like particles, T-cell-inducing peptides and recombinant proteins, synthetic viruses, broadly neutralizing antibodies, and nucleic acid-based vaccines. This review discusses recent scientific advances in the development of next-generation universal influenza vaccines.
Poumbourios, P.; Jackson, D.C.; Oxford, J.S.
The antibody response of mice and adult humans to immunization with subunit vaccines derived from a pair of antigenically distinct influenza A H1N1 viruses isolate in eggs was investigated. Although the haemagglutinin molecule of each virus differed by only three amino acid residues, highly specific antibody responses were elicited in mice as determined by haemagglutination inhibition and radioimmunoprecipitation assays. Results from competitive radioimmunoassays using monoclonal antibodies of known specificity and a study of the reactivity of mouse antisera with H1N1 field strains indicated that the marked differences in the antibody responses to the two vaccines was due to an amino acid substitution in the distal tip of the haemagglutinin molecule. In contrast, cross reactive antibody responses were elicited in humans presumably due to exposure to viruses related to the candidate vaccine prior to vaccination. Although immunogenic differences are apparent in this pair of antigenically distinct viruses in naive laboratory animals, these differences are not apparent following vaccination of humans that had prior exposure to related viruses. 21 refs., 5 tabs., 4 figs
Zuccotti, Gian Vincenzo; Fabiano, Valentina
Influenza represents a major sanitary and socio-economic burden and vaccination is universally considered the most effective strategy for preventing the disease and its complications. Traditional influenza vaccines have been on the market since the late 1940s, with million of doses administered annually worldwide, and demonstrated a substantial efficacy and safety. The trivalent inactivated subunit vaccine has been available for more than 25 years and has been studied in healthy children, adults and the elderly and in people affected by underlying chronic medical conditions. We describe vaccine technology focusing on subunit vaccine production procedures and mode of action and provide updated information on efficacy and safety available data. A review of efficacy and safety data in healthy subjects and in high risk populations from major sponsor- and investigator-driven studies. The vaccine showed a good immunogenicity and a favorable safety profile in all target groups. In the panorama of actually available influenza vaccines, trivalent inactivated subunit vaccine represents a well-established tool for preventing flu and the associated complications.
Boyle, D B; Selleck, P; Heine, H G
To evaluate the vaccine efficacy of a fowlpox virus recombinant expressing the H7 haemagglutinin of avian influenza virus in poultry. Specific-pathogen-free poultry were vaccinated with fowlpox recombinants expressing H7 or H1 haemagglutinins of influenza virus. Chickens were vaccinated at 2 or 7 days of age and challenged with virulent Australian avian influenza virus at 10 and 21 days later, respectively. Morbidity and mortality, body weight change and the development of immune responses to influenza haemagglutinin and nucleoprotein were recorded. Vaccination of poultry with fowlpox H7 avian influenza virus recombinants induced protective immune responses. All chickens vaccinated at 7 days of age and challenged 21 days later were protected from death. Few clinical signs of infection developed. In contrast, unvaccinated or chickens vaccinated with a non-recombinant fowlpox or a fowlpox expressing the H1 haemagglutinin of human influenza were highly susceptible to avian influenza. All those chickens died within 72 h of challenge. In younger chickens, vaccinated at 2 days of age and challenged 10 days later the protection was lower with 80% of chickens protected from death. Chickens surviving vaccination and challenge had high antibody responses to haemagglutinin and primary antibody responses to nucleoprotein suggesting that although vaccination protected substantially against disease it failed to completely prevent replication of the challenge avian influenza virus. Vaccination of chickens with fowlpox virus expressing the avian influenza H7 haemagglutinin provided good protection against experimental challenge with virulent avian influenza of H7 type. Although eradication will remain the method of first choice for control of avian influenza, in the circumstances of a continuing and widespread outbreak the availability of vaccines based upon fowlpox recombinants provides an additional method for disease control.
Full Text Available 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.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.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.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.Parents perceived advantages and disadvantages to delivering annual seasonal
Scallan, Ciaran D; Lindbloom, Jonathan D; Tucker, Sean N
Oral vaccines delivered as tablets offer a number of advantages over traditional parenteral-based vaccines including the ease of delivery, lack of needles, no need for trained medical personnel, and the ability to formulate into temperature-stable tablets. We have been evaluating an oral vaccine platform based on recombinant adenoviral vectors for the purpose of creating a prophylactic vaccine to prevent influenza, and have demonstrated vaccine efficacy in animal models and substantial immunogenicity in humans. These studies have evaluated monovalent vaccines to date. To protect against the major circulating A and B influenza strains, a multivalent influenza vaccine will be required. In this study, the immunogenicity of orally delivered monovalent, bivalent, trivalent, and quadrivalent vaccines was tested in ferrets and mice. The various vaccine combinations were tested by blending monovalent recombinant adenovirus vaccines, each expressing hemagglutinin from a single strain. Human tablet delivery was modeled in animals by oral gavage in mice and by endoscopic delivery in ferrets. We demonstrated minimal interference between the various vaccine vectors when used in combination and that the oral quadrivalent vaccine compared favorably to an approved trivalent inactivated vaccine. The quadrivalent vaccine presented here produced immune responses that we predict should be capable of providing protection against multiple influenza strains, and the platform should have applications to other multivalent vaccines. Vaxart, Inc.
Jefferson, Tom; Rivetti, Alessandro; Di Pietrantonj, Carlo; Demicheli, Vittorio
The consequences of influenza in children and adults are mainly absenteeism from school and work. However, the risk of complications is greatest in children and people over 65 years of age. This is an update of a review published in 2011. Future updates of this review will be made only when new trials or vaccines become available. Observational data included in previous versions of the review have been retained for historical reasons but have not been updated because of their lack of influence on the review conclusions. To assess the effects (efficacy, effectiveness, and harm) of vaccines against influenza in healthy children. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library 2016, Issue 12), which includes the Cochrane Acute Respiratory Infections Group Specialised Register, MEDLINE (1966 to 31 December 2016), Embase (1974 to 31 December 2016), WHO International Clinical Trials Registry Platform (ICTRP; 1 July 2017), and ClinicalTrials.gov (1 July 2017). Randomised controlled trials comparing influenza vaccines with placebo or no intervention in naturally occurring influenza in healthy children under 16 years. Previous versions of this review included 19 cohort and 11 case-control studies. We are no longer updating the searches for these study designs but have retained the observational studies for historical purposes. Review authors independently assessed risk of bias and extracted data. We used GRADE to rate the certainty of evidence for the key outcomes of influenza, influenza-like illness (ILI), complications (hospitalisation, ear infection), and adverse events. Due to variation in control group risks for influenza and ILI, absolute effects are reported as the median control group risk, and numbers needed to vaccinate (NNVs) are reported accordingly. For other outcomes aggregate control group risks are used. We included 41 clinical trials (> 200,000 children). Most of the studies were conducted in children over the
Shim, Eunha; Brown, Shawn T; DePasse, Jay; Nowalk, Mary Patricia; Raviotta, Jonathan M; Smith, Kenneth J; Zimmerman, Richard K
Prior studies showed that live attenuated influenza vaccine (LAIV) is more effective than inactivated influenza vaccine (IIV) in children aged 2-8 years, supporting the Centers for Disease Control and Prevention (CDC) recommendations in 2014 for preferential LAIV use in this age group. However, 2014-2015 U.S. effectiveness data indicated relatively poor effectiveness of both vaccines, leading CDC in 2015 to no longer prefer LAIV. An age-structured model of influenza transmission and vaccination was developed, which incorporated both direct and indirect protection induced by vaccination. Based on this model, the cost effectiveness of influenza vaccination strategies in children aged 2-8 years in the U.S. was estimated. The base case assumed a mixed vaccination strategy where 33.3% and 66.7% of vaccinated children aged 2-8 years receive LAIV and IIV, respectively. Analyses were performed in 2014-2015. Using published meta-analysis vaccine effectiveness data (83% LAIV and 64% IIV), exclusive LAIV use would be a cost-effective strategy when vaccinating children aged 2-8 years, whereas IIV would not be preferred. However, when 2014-2015 U.S. effectiveness data (0% LAIV and 15% IIV) were used, IIV was likely to be preferred. The cost effectiveness of influenza vaccination in children aged 2-8 years is highly dependent on vaccine effectiveness; the vaccine type with higher effectiveness is preferred. In general, exclusive IIV use is preferred over LAIV use, as long as vaccine effectiveness is higher for IIV than for LAIV. Copyright © 2016 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.
Kwon, Ji-Sun; Yoon, Jungsoon; Kim, Yeon-Jung; Kang, Kyuho; Woo, Sunje; Jung, Dea-Im; Song, Man Ki; Kim, Eun-Ha; Kwon, Hyeok-Il; Choi, Young Ki; Kim, Jihye; Lee, Jeewon; Yoon, Yeup; Shin, Eui-Cheol; Youn, Jin-Won
Growing concerns about unpredictable influenza pandemics require a broadly protective vaccine against diverse influenza strains. One of the promising approaches was a T cell-based vaccine, but the narrow breadth of T-cell immunity due to the immunodominance hierarchy established by previous influenza infection and efficacy against only mild challenge condition are important hurdles to overcome. To model T-cell immunodominance hierarchy in humans in an experimental setting, influenza-primed C57BL/6 mice were chosen and boosted with a mixture of vaccinia recombinants, individually expressing consensus sequences from avian, swine, and human isolates of influenza internal proteins. As determined by IFN-γ ELISPOT and polyfunctional cytokine secretion, the vaccinia recombinants of influenza expanded the breadth of T-cell responses to include subdominant and even minor epitopes. Vaccine groups were successfully protected against 100 LD50 challenges with PR/8/34 and highly pathogenic avian influenza H5N1, which contained the identical dominant NP366 epitope. Interestingly, in challenge with pandemic A/Cal/04/2009 containing mutations in the dominant epitope, only the group vaccinated with rVV-NP + PA showed improved protection. Taken together, a vaccinia-based influenza vaccine expressing conserved internal proteins improved the breadth of influenza-specific T-cell immunity and provided heterosubtypic protection against immunologically close as well as distant influenza strains. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Loeffen, W.L.A.; Stockhofe-Zurwieden, N.; Weesendorp, E.; Zoelen-Bos, van D.J.; Heutink, R.; Quak, J.; Goovaerts, D.; Heldens, J.; Maas, H.A.; Moormann, R.J.M.; Koch, G.
In April 2009 a new influenza A/H1N1 strain, currently named “pandemic (H1N1) influenza 2009¿ (H1N1v), started the first official pandemic in humans since 1968. Several incursions of this virus in pig herds have also been reported from all over the world. Vaccination of pigs may be an option to
Full Text Available ABSTRACTBACKGROUND: This is an update of the original review published in 2008. The risk of adverse cardiovascular outcomes is increased with influenza-like infection, and vaccination against influenza may improve cardiovascular outcomes.OBJECTIVES: To assess the potential benefits of influenza vaccination for primary and secondary prevention of cardiovascular disease.METHODS:Search methods:We searched the following electronic databases on 18 October 2013: The Cochrane Library (including Cochrane Central Register of Controlled Trials (CENTRAL, Database of Abstracts of Reviews of Effects (DARE, Economic Evaluation Database (EED and Health Technology Assessment database (HTA, MEDLINE, EMBASE, Science Citation Index Expanded, Conference Proceedings Citation Index - Science and ongoing trials registers (www.controlled-trials.com/ and www.clinicaltrials.gov. We examined reference lists of relevant primary studies and systematic reviews. We performed a limited PubMed search on 20 February 2015, just before publication.Selection criteria:Randomised controlled trials (RCTs of influenza vaccination compared with placebo or no treatment in participants with or without cardiovascular disease, assessing cardiovascular death or non-fatal cardiovascular events.Data collection and analysis:We used standard methodological procedures as expected by The Cochrane Collaboration. We carried out meta-analyses only for cardiovascular death, as other outcomes were reported too infrequently. We expressed effect sizes as risk ratios (RRs, and we used random-effects models.MAIN RESULTS: We included eight trials of influenza vaccination compared with placebo or no vaccination, with 12,029 participants receiving at least one vaccination or control treatment. We included six new studies (n = 11,251, in addition to the two included in the previous version of the review. Four of these trials (n = 10,347 focused on prevention of influenza in the general or elderly population
Clar, Christine; Oseni, Zainab; Flowers, Nadine; Keshtkar-Jahromi, Maryam; Rees, Karen
This is an update of the original review published in 2008. The risk of adverse cardiovascular outcomes is increased with influenza-like infection, and vaccination against influenza may improve cardiovascular outcomes. To assess the potential benefits of influenza vaccination for primary and secondary prevention of cardiovascular disease. We searched the following electronic databases on 18 October 2013: The Cochrane Library (including Cochrane Central Register of Controlled Trials (CENTRAL), Database of Abstracts of Reviews of Effects (DARE), Economic Evaluation Database (EED) and Health Technology Assessment database (HTA)), MEDLINE, EMBASE, Science Citation Index Expanded, Conference Proceedings Citation Index - Science and ongoing trials registers (www.controlled-trials.com/ and www.clinicaltrials.gov). We examined reference lists of relevant primary studies and systematic reviews. We performed a limited PubMed search on 20 February 2015, just before publication. Randomised controlled trials (RCTs) of influenza vaccination compared with placebo or no treatment in participants with or without cardiovascular disease, assessing cardiovascular death or non-fatal cardiovascular events. We used standard methodological procedures as expected by The Cochrane Collaboration. We carried out meta-analyses only for cardiovascular death, as other outcomes were reported too infrequently. We expressed effect sizes as risk ratios (RRs), and we used random-effects models. We included eight trials of influenza vaccination compared with placebo or no vaccination, with 12,029 participants receiving at least one vaccination or control treatment. We included six new studies (n = 11,251), in addition to the two included in the previous version of the review. Four of these trials (n = 10,347) focused on prevention of influenza in the general or elderly population and reported cardiovascular outcomes among their safety analyses; four trials (n = 1682) focused on prevention of
Murugappan, Senthil; Patil, Harshad P; Frijlink, Henderik W; Huckriede, Anke; Hinrichs, Wouter L J
The best approach to control the spread of influenza virus during a pandemic is vaccination. Yet, an appropriate vaccine is not available early in the pandemic since vaccine production is time consuming. For influenza strains with a high pandemic potential like H5N1, stockpiling of vaccines has been
Global guidelines strongly recommend annual influenza vaccination in people age 6 months and older, particularly in asthmatic children. There is no doubt about the benefit of influenza vaccination in asthmatic children. However, some of the vaccine's components may elicit an IgE mediated hypersensitivity or disease exacerbation, including life-threatening events, in children with allergic diseases. As a result, concerns regarding the safety of the vaccine still continue today. The influenza v...
Lee, Bruce Y; Tai, Julie H Y; Bailey, Rachel R; Smith, Kenneth J; Nowalk, Andrew J
To determine how much should be invested each year to encourage and operationalize the administration of influenza vaccine to children before November and how late the vaccine should be offered each year. Monte Carlo decision analytic computer simulation models. The children's influenza vaccination timing model quantified the incremental economic value of vaccinating a child earlier in the influenza season and the incremental cost of delaying vaccination. The children's monthly influenza vaccination decision model evaluated the cost-effectiveness of vaccinating versus not vaccinating for every month of the influenza season. Getting children vaccinated by the end of October rather than when they are currently getting vaccinated could save society between $6.4 million and $9.2 million plus 653 and 926 quality-adjusted life-years (QALYs) and third-party payers between $4.1 million and $6.1 million plus 647 to 942 QALYs each year. Decision makers may want to continue offering influenza vaccination to children at least through the end of December. Vaccinating with trivalent inactivated virus vaccine was more cost-effective than vaccinating with live attenuated influenza vaccine for every month. Policymakers could invest up to $6 million to $9 million a year to get children vaccinated in September or October without expending any net costs.
a history of prior vaccination. Keywords: COPD, human influenza, humoral immunity, influenza vaccines, vaccination
Van Buynder, Paul G.; Carcione, Dale; Rettura, Vince; Daly, Alison; Woods, Emily
Please cite this paper as: Van Buynder et al. (2010) Marketing paediatric influenza vaccination: results of a major metropolitan trial. Influenza and Other Respiratory Viruses 5(1), 33–38. Objectives After a cluster of rapidly fulminant influenza related toddler deaths in a Western Australian metropolis, children aged six to 59 months were offered influenza vaccination in subsequent winters. Some parental resistance was expected and previous poor uptake of paediatric influenza vaccination overseas was noted. A marketing campaign addressing barriers to immunization was developed to maximise uptake. Design Advertising occurred in major statewide newspapers, via public poster displays and static ‘eye‐lite’ displays, via press releases, via a series of rolling radio advertisements, via direct marketing to child care centres, and via a linked series of web‐sites. Parents were subsequently surveyed to assess reasons for vaccination. Main Outcome Results The campaign produced influenza vaccination coverage above that previously described elsewhere and led to a proportionate reduction in influenza notifications in this age group compared to previous seasons. Conclusions Influenza in children comes with significant morbidity and some mortality. Paediatric influenza vaccination is safe, well tolerated and effective if two doses are given. A targeted media campaign can increase vaccine uptake if it reinforces the seriousness of influenza and addresses community ‘myths’ about influenza and influenza vaccine. The lessons learned enabling enhancements of similar programs elsewhere. PMID:21138538
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
Full Text Available BACKGROUND: The threat of avian influenza and the 2004-2005 influenza vaccine supply shortage in the United States have sparked a debate about optimal vaccination strategies to reduce the burden of morbidity and mortality caused by the influenza virus. METHODS AND FINDINGS: We present a comparative analysis of two classes of suggested vaccination strategies: mortality-based strategies that target high-risk populations and morbidity-based strategies that target high-prevalence populations. Applying the methods of contact network epidemiology to a model of disease transmission in a large urban population, we assume that vaccine supplies are limited and then evaluate the efficacy of these strategies across a wide range of viral transmission rates and for two different age-specific mortality distributions. We find that the optimal strategy depends critically on the viral transmission level (reproductive rate of the virus: morbidity-based strategies outperform mortality-based strategies for moderately transmissible strains, while the reverse is true for highly transmissible strains. These results hold for a range of mortality rates reported for prior influenza epidemics and pandemics. Furthermore, we show that vaccination delays and multiple introductions of disease into the community have a more detrimental impact on morbidity-based strategies than mortality-based strategies. CONCLUSIONS: If public health officials have reasonable estimates of the viral transmission rate and the frequency of new introductions into the community prior to an outbreak, then these methods can guide the design of optimal vaccination priorities. When such information is unreliable or not available, as is often the case, this study recommends mortality-based vaccination priorities.
Full Text Available Ferrets are a useful animal model for human influenza virus infections, since they closely mimic the pathogenesis of influenza viruses observed in humans. However, a lack of reagents, especially for flow cytometry of immune cell subsets, has limited research in this model. Here we use a panel of primarily species cross-reactive antibodies to identify ferret T cells, cytotoxic T lymphocytes (CTL, B cells, and granulocytes in peripheral blood. Following infection with seasonal H3N2 or H1N1pdm09 influenza viruses, these cell types showed rapid and dramatic changes in frequency, even though clinically the infections were mild. The loss of B cells and CD4 and CD8 T cells, and the increase in neutrophils, were especially marked 1-2 days after infection, when about 90% of CD8+ T cells disappeared from the peripheral blood. The different virus strains led to different kinetics of leukocyte subset alterations. Vaccination with homologous vaccine reduced clinical symptoms slightly, but led to a much more rapid return to normal leukocyte parameters. Assessment of clinical symptoms may underestimate the effectiveness of influenza vaccine in restoring homeostasis.
Music, Nedzad; Reber, Adrian J; Lipatov, Aleksandr S; Kamal, Ram P; Blanchfield, Kristy; Wilson, Jason R; Donis, Ruben O; Katz, Jacqueline M; York, Ian A
Ferrets are a useful animal model for human influenza virus infections, since they closely mimic the pathogenesis of influenza viruses observed in humans. However, a lack of reagents, especially for flow cytometry of immune cell subsets, has limited research in this model. Here we use a panel of primarily species cross-reactive antibodies to identify ferret T cells, cytotoxic T lymphocytes (CTL), B cells, and granulocytes in peripheral blood. Following infection with seasonal H3N2 or H1N1pdm09 influenza viruses, these cell types showed rapid and dramatic changes in frequency, even though clinically the infections were mild. The loss of B cells and CD4 and CD8 T cells, and the increase in neutrophils, were especially marked 1-2 days after infection, when about 90% of CD8+ T cells disappeared from the peripheral blood. The different virus strains led to different kinetics of leukocyte subset alterations. Vaccination with homologous vaccine reduced clinical symptoms slightly, but led to a much more rapid return to normal leukocyte parameters. Assessment of clinical symptoms may underestimate the effectiveness of influenza vaccine in restoring homeostasis.
... Committee Healthcare Personnel Influenza Vaccination Subgroup's Draft Report and Draft Recommendations for Achieving the Healthy People 2020 Annual Coverage Goals for Influenza Vaccination in Healthcare Personnel... Influenza Vaccination Subgroup (HCPIVS), will host an informational webinar to introduce the committee's...
Gefenaite, G.; Tacken, M.; Bos, J.; Stirbu-Wagner, I.; Korevaar, J.C.; Stolk, R.P.; Wolters, B.; Bijl, M.; Postma, M.J.; Wilschut, J.; Nichol, K.L.; Hak, E.
Introduction: Because of variability in published A(H1N1)pdm09 influenza vaccine effectiveness estimates, we conducted a study in the adults belonging to the risk groups to assess the A(H1N1)pdm09 MF59-adjuvanted influenza vaccine effectiveness. Methods: VE against influenza and/or pneumonia was
U.S. Department of Health & Human Services — This dataset includes facility details, measure score, and the state and national average measure scores for the NHSN healthcare personnel influenza vaccination...
Mistilis, Matthew; 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 HEPES buffer salts stabilized influenza vaccine, surfactants had little effect during drying, drying temperature had weak effects on vaccine stability, and drying on polydimethylsiloxane led to increased stability compared to 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 six 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. PMID:25448542
De Keyser, J; Zwanikken, C
Despite reports that influenza vaccination appears to be safe in multiple sclerosis there is uncertainty which patients may benefit from it. By using a questionnaire we compared the effects of influenza illness (1995-1996 season) and influenza vaccination (autumn of 1996) on neurologic symptoms in
Gauger, Phillip C; Vincent, Amy L; Loving, Crystal L; Lager, Kelly M; Janke, Bruce H; Kehrli, Marcus E; Roth, James A
Influenza is an economically important respiratory disease affecting swine world-wide with potential zoonotic implications. Genetic reassortment and drift has resulted in genetically and antigenically distinct swine influenza viruses (SIVs). Consequently, prevention of SIV infection is challenging due to the increased rate of genetic change and a potential lack of cross-protection between vaccine strains and circulating novel isolates. This report describes a vaccine-heterologous challenge model in which pigs were administered an inactivated H1N2 vaccine with a human-like (δ-cluster) H1 six and three weeks before challenge with H1 homosubtypic, heterologous 2009 pandemic H1N1. At necropsy, macroscopic and microscopic pneumonia scores were significantly higher in the vaccinated and challenged (Vx/Ch) group compared to non-vaccinated and challenged (NVx/Ch) pigs. The Vx/Ch group also demonstrated enhanced clinical disease and a significantly elevated pro-inflammatory cytokine profile in bronchoalveolar lavage fluid compared to the NVx/Ch group. In contrast, viral shedding and replication were significantly higher in NVx/Ch pigs although all challenged pigs, including Vx/Ch pigs, were shedding virus in nasal secretions. Hemagglutination inhibition (HI) and serum neutralizing (SN) antibodies were detected to the priming antigen in the Vx/Ch pigs but no measurable cross-reacting HI or SN antibodies were detected to pandemic H1N1 (pH1N1). Overall, these results suggest that inactivated SIV vaccines may potentiate clinical signs, inflammation and pneumonia following challenge with divergent homosubtypic viruses that do not share cross-reacting HI or SN antibodies. Published by Elsevier Ltd.
Scorza, Francesco Berlanda; Pardi, Norbert
RNA-based immunization strategies have emerged as promising alternatives to conventional vaccine approaches. A substantial body of published work demonstrates that RNA vaccines can elicit potent, protective immune responses against various pathogens. Consonant with its huge impact on public health, influenza virus is one of the best studied targets of RNA vaccine research. Currently licensed influenza vaccines show variable levels of protection against seasonal influenza virus strains but are inadequate against drifted and pandemic viruses. In recent years, several types of RNA vaccines demonstrated efficacy against influenza virus infections in preclinical models. Additionally, comparative studies demonstrated the superiority of some RNA vaccines over the currently used inactivated influenza virus vaccines in animal models. Based on these promising preclinical results, clinical trials have been initiated and should provide valuable information about the translatability of the impressive preclinical data to humans. This review briefly describes RNA-based vaccination strategies, summarizes published preclinical and clinical data, highlights the roadblocks that need to be overcome for clinical applications, discusses the landscape of industrial development, and shares the authors' personal perspectives about the future of RNA-based influenza virus vaccines.
Miles, John J.; Tan, Mai Ping; Dolton, Garry; Galloway, Sarah A.E.; Laugel, Bruno; Makinde, Julia; Matthews, Katherine K.; Watkins, Thomas S.; Wong, Yide; Clark, Richard J.; Pentier, Johanne M.; Attaf, Meriem; Lissina, Anya; Ager, Ann; Gallimore, Awen; Gras, Stephanie; Rossjohn, Jamie; Burrows, Scott R.; Cole, David K.; Price, David A.
Polypeptide vaccines effectively activate human T cells but suffer from poor biological stability, which confines both transport logistics and in vivo therapeutic activity. Synthetic biology has the potential to address these limitations through the generation of highly stable antigenic “mimics” using subunits that do not exist in the natural world. We developed a platform based on D–amino acid combinatorial chemistry and used this platform to reverse engineer a fully artificial CD8+ T cell agonist that mirrored the immunogenicity profile of a native epitope blueprint from influenza virus. This nonnatural peptide was highly stable in human serum and gastric acid, reflecting an intrinsic resistance to physical and enzymatic degradation. In vitro, the synthetic agonist stimulated and expanded an archetypal repertoire of polyfunctional human influenza virus–specific CD8+ T cells. In vivo, specific responses were elicited in naive humanized mice by subcutaneous vaccination, conferring protection from subsequent lethal influenza challenge. Moreover, the synthetic agonist was immunogenic after oral administration. This proof-of-concept study highlights the power of synthetic biology to expand the horizons of vaccine design and therapeutic delivery. PMID:29528337
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.
Childress, Billy-Clyde; Montney, Joshua D; Albro, Elise A
Years ago, intramuscular influenza vaccines were the only option for those who wanted to arm themselves against the flu. Today there are alternatives, including intradermal injections and intranasal sprays. In order to select the right influenza vaccine for their patients, pharmacists, and other healthcare professionals must have a basic understanding of the immune system. Influenza vaccines elicit different levels of immune response involving innate and adaptive immunity, which are critical ...
Peter T Loudon
Full Text Available The recent H5N1 avian and H1N1 swine-origin influenza virus outbreaks reaffirm that the threat of a world-wide influenza pandemic is both real and ever-present. Vaccination is still considered the best strategy for protection against influenza virus infection but a significant challenge is to identify new vaccine approaches that offer accelerated production, broader protection against drifted and shifted strains, and the capacity to elicit anti-viral immune responses in the respiratory tract at the site of viral entry. As a safe alternative to live attenuated vaccines, the mucosal and systemic immunogenicity of an H1N1 influenza (A/New Caledonia/20/99 HA DNA vaccine administered by particle-mediated epidermal delivery (PMED or gene gun was analyzed in rhesus macaques.Macaques were immunized at weeks 0, 8, and 16 using a disposable single-shot particle-mediated delivery device designed for clinical use that delivers plasmid DNA directly into cells of the epidermis. Significant levels of hemagglutination inhibiting (HI antibodies and cytokine-secreting HA-specific T cells were observed in the periphery of macaques following 1-3 doses of the PMED HA DNA vaccine. In addition, HA DNA vaccination induced detectable levels of HA-specific mucosal antibodies and T cells in the lung and gut-associated lymphoid tissues of vaccinated macaques. Importantly, co-delivery of a DNA encoding the rhesus macaque GM-CSF gene was found to significantly enhance both the systemic and mucosal immunogenicity of the HA DNA vaccine.These results provide strong support for the development of a particle-mediated epidermal DNA vaccine for protection against respiratory pathogens such as influenza and demonstrate, for the first time, the ability of skin-delivered GM-CSF to serve as an effective mucosal adjuvant for vaccine induction of immune responses in the gut and respiratory tract.
Why get vaccinated?HPV vaccine prevents infection with human papillomavirus (HPV) types that are associated with cause ... at http://www.cdc.gov/hpv. HPV Vaccine (Human Papillomavirus) Information Statement. U.S. Department of Health and ...
Phillips, Michael; Cataneo, Renee N; Chaturvedi, Anirudh; Danaher, Patrick J; Devadiga, Anantrai; Legendre, David A; Nail, Kim L; Schmitt, Peter; Wai, James
Viral infections cause increased oxidative stress, so a breath test for oxidative stress biomarkers (alkanes and alkane derivatives) might provide a new tool for early diagnosis. We studied 33 normal healthy human subjects receiving scheduled treatment with live attenuated influenza vaccine (LAIV). Each subject was his or her own control, since they were studied on day 0 prior to vaccination, and then on days 2, 7 and 14 following vaccination. Breath volatile organic compounds (VOCs) were collected with a breath collection apparatus, then analyzed by automated thermal desorption with gas chromatography and mass spectroscopy. A Monte Carlo simulation technique identified non-random VOC biomarkers of infection based on their C-statistic values (area under curve of receiver operating characteristic). Treatment with LAIV was followed by non-random changes in the abundance of breath VOCs. 2, 8-Dimethyl-undecane and other alkane derivatives were observed on all days. Conservative multivariate models identified vaccinated subjects on day 2 (C-statistic = 0.82, sensitivity = 63.6% and specificity = 88.5%); day 7 (C-statistic = 0.94, sensitivity = 88.5% and specificity = 92.3%); and day 14 (C-statistic = 0.95, sensitivity = 92.3% and specificity = 92.3%). The altered breath VOCs were not detected in live attenuated influenza vaccine, excluding artifactual contamination. LAIV vaccination in healthy humans elicited a prompt and sustained increase in breath biomarkers of oxidative stress. A breath test for these VOCs could potentially identify humans who are acutely infected with influenza, but who have not yet developed clinical symptoms or signs of disease.
Doroshenko, Alexander; Halperin, Scott A
Annual influenza epidemics continue to have a considerable impact in both developed and developing countries. Vaccination remains the principal measure to prevent seasonal influenza and reduce associated morbidity and mortality. The WHO recommends using established mammalian cell culture lines as an alternative to egg-based substrates in the manufacture of influenza vaccine. In June 2007, the EMEA approved Optaflu, a Madin Darby canine kidney cell culture-derived influenza vaccine manufactured by Novartis Vaccines. This review examines the advantages and disadvantages of cell culture-based technology for influenza vaccine production, compares immunogenicity and safety data for Optaflu with that of currently marketed conventional egg-based influenza vaccines, and considers the prospects for wider use of cell culture-based influenza vaccines.
Alexander W Kay
Full Text Available Pregnant women are at high risk from influenza due to disproportionate morbidity, mortality, and adverse pregnancy outcomes following infection. As such, they are classified as a high priority group for vaccination. However, changes in the maternal immune system required to accommodate the allogeneic fetus may alter the immunogenicity of influenza vaccines. A large number of studies have evaluated the safety of the influenza vaccine. Here, we will review available studies on the immunogenicity and efficacy of the influenza vaccine during pregnancy, focusing on both humoral and cellular immunity.
Soema, Peter Christiaan
Current seasonal influenza vaccines rely on the induction of antibodies to neutralize the virus. However, influenza viruses frequently undergo genetic mutations due to antigenic drift and shift, altering the surface proteins hemagglutinin and neuraminidase to which antibodies usually bind. This
Vaccination against influenza is the most effective approach for reducing influenza morbidity and mortality. However, influenza vaccines are unique among all licensed vaccines as they are updated and administered annually to antigenically match the vaccine strains and currently circulating influenza strains. Vaccine efficacy of each selected influenza virus vaccine varies depending on the antigenic match between circulating strains and vaccine strains, as well as the age and health status of the vaccine recipient. Low vaccine effectiveness of seasonal influenza vaccines in recent years provides an impetus to improve current seasonal influenza vaccines, and for development of next-generation influenza vaccines that can provide broader, long-lasting protection against both matching and antigenically diverse influenza strains. This review discusses a perspective on some of the issues and formidable challenges facing the development and regulation of the next-generation influenza vaccines.
Dyah Ayu Hewajuli
Full Text Available Influenza A virus is a hazardous virus and harm to respiratory tract. The virus infect birds, pigs, horses, dogs, mammals and humans. Pigs are important hosts in ecology of the influenza virus because they have two receptors, namely NeuAc 2,3Gal and NeuAc 2,6Gal which make the pigs are sensitive to infection of influenza virus from birds and humans and genetic reassortment can be occurred. Classical swine influenza H1N1 viruses had been circulated in pigs in North America and other countries for 80 years. In 1998, triple reassortant H3N2 swine influenza viruses that contains genes of human influenza A virus (H3N2, swine influenza virus (H1N1 and avian influenza are reported as cause an outbreaks in pigs in North America. Furthermore, the circulation of triple reassortant H3N2 swine influenza virus resulting reassortant H1N1 swine influenza and reassortant H1N2 swine influenza viruses cause infection in humans. Humans who were infected by triple reassortant swine influenza A virus (H1N1 usually made direct contact with pigs. Although without any clinical symptoms, pigs that are infected by triple reassortant swine influenza A (H1N1 can transmit infection to the humans around them. In June 2009, WHO declared that pandemic influenza of reassortant H1N1 influenza A virus (novel H1N1 has reached phase 6. In Indonesia until 2009, there were 1005 people were infected by H1N1 influenza A and 5 of them died. Novel H1N1 and H5N1 viruses have been circulated in humans and pigs in Indonesia. H5N1 reassortant and H1N1 viruses or the seasonal flu may could arise because of genetic reassortment between avian influenza and humans influenza viruses that infect pigs together.
Full Text Available Due to frequent viral antigenic change, current influenza vaccines need to be re-formulated annually to match the circulating strains for battling seasonal influenza epidemics. These vaccines are also ineffective in preventing occasional outbreaks of new influenza pandemic viruses. All these challenges call for the development of universal influenza vaccines capable of conferring broad cross-protection against multiple subtypes of influenza A viruses. Facilitated by the advancement in modern molecular biology, delicate antigen design becomes one of the most effective factors for fulfilling such goals. Conserved epitopes residing in virus surface proteins including influenza matrix protein 2 and the stalk domain of the hemagglutinin draw general interest for improved antigen design. The present review summarizes the recent progress in such endeavors and also covers the encouraging progress in integrated antigen/adjuvant delivery and controlled release technology that facilitate the development of an affordable universal influenza vaccine.
Khazeni, Nayer; Hutton, David W; Collins, Cassandra I F; Garber, Alan M; Owens, Douglas K
Vaccination for the 2009 pandemic did not occur until late in the outbreak, which limited its benefits. Influenza A (H7N9) is causing increasing morbidity and mortality in China, and researchers have modified the A (H5N1) virus to transmit via aerosol, which again heightens concerns about pandemic influenza preparedness. To determine how quickly vaccination should be completed to reduce infections, deaths, and health care costs in a pandemic with characteristics similar to influenza A (H7N9) and A (H5N1). Dynamic transmission model to estimate health and economic consequences of a severe influenza pandemic in a large metropolitan city. Literature and expert opinion. Residents of a U.S. metropolitan city with characteristics similar to New York City. Lifetime. Societal. Vaccination of 30% of the population at 4 or 6 months. Infections and deaths averted and cost-effectiveness. In 12 months, 48 254 persons would die. Vaccinating at 9 months would avert 2365 of these deaths. Vaccinating at 6 months would save 5775 additional lives and $51 million at a city level. Accelerating delivery to 4 months would save an additional 5633 lives and $50 million. If vaccination were delayed for 9 months, reducing contacts by 8% through nonpharmaceutical interventions would yield a similar reduction in infections and deaths as vaccination at 4 months. The model is not designed to evaluate programs targeting specific populations, such as children or persons with comorbid conditions. Vaccination in an influenza A (H7N9) pandemic would need to be completed much faster than in 2009 to substantially reduce morbidity, mortality, and health care costs. Maximizing non-pharmaceutical interventions can substantially mitigate the pandemic until a matched vaccine becomes available. Agency for Healthcare Research and Quality, National Institutes of Health, and Department of Veterans Affairs.
Kumar, Arun; Meldgaard, Trine Sundebo; Bertholet, Sylvie
Despite advancements in immunotherapeutic approaches, influenza continues to cause severe illness, particularly among immunocompromised individuals, young children, and elderly adults. Vaccination is the most effective way to reduce rates of morbidity and mortality caused by influenza viruses....... Frequent genetic shift and drift among influenzavirus strains with the resultant disparity between circulating and vaccine virus strains limits the effectiveness of the available conventional influenza vaccines. One approach to overcome this limitation is to develop a universal influenza vaccine that could...... provide protection against all subtypes of influenza viruses. Moreover, the development of a novel or improved universal influenza vaccines may be greatly facilitated by new technologies including virus-like particles, T-cell-inducing peptides and recombinant proteins, synthetic viruses, broadly...
Van Buynder, Paul G; Carcione, Dale; Rettura, Vince; Daly, Alison; Woods, Emily
After a cluster of rapidly fulminant influenza related toddler deaths in a Western Australian metropolis, children aged six to 59 months were offered influenza vaccination in subsequent winters. Some parental resistance was expected and previous poor uptake of paediatric influenza vaccination overseas was noted. A marketing campaign addressing barriers to immunization was developed to maximise uptake. Advertising occurred in major statewide newspapers, via public poster displays and static 'eye-lite' displays, via press releases, via a series of rolling radio advertisements, via direct marketing to child care centres, and via a linked series of web-sites. Parents were subsequently surveyed to assess reasons for vaccination. The campaign produced influenza vaccination coverage above that previously described elsewhere and led to a proportionate reduction in influenza notifications in this age group compared to previous seasons. Influenza in children comes with significant morbidity and some mortality. Paediatric influenza vaccination is safe, well tolerated and effective if two doses are given. A targeted media campaign can increase vaccine uptake if it reinforces the seriousness of influenza and addresses community 'myths' about influenza and influenza vaccine. The lessons learned enabling enhancements of similar programs elsewhere. © 2010 Blackwell Publishing Ltd.
Cohen, Steven A.; Chui, Kenneth K.H.; Naumova, Elena N.
OBJECTIVES To assess how influenza vaccination coverage in children is related to pneumonia and influenza (P&I) in US seniors and if these associations are modified by sociodemographic factors. DESIGN We abstracted approximately 5 million hospitalization records from the Centers for Medicare and Medicaid Services for four influenza years, 2002–2006. We estimated a single year age distribution of rates of P&I hospitalization by state for each influenza season and observed an exponential acceleration in the P&I rates with age for each influenza season. State-and season-specific P&I rate accelerations were regressed against the percentage of vaccinated children, seniors, or both using mixed effects models. SETTING United States population, 2002–2006 PARTICIPANTS US population aged 65 and above MEASUREMENTS State-level influenza annual vaccination coverage data in children and seniors were obtained from the National Immunization Survey and the Behavioral Risk Factor Surveillance System, respectively. RESULTS Child influenza vaccination coverage was negatively associated with age acceleration in P&I, whereas influenza vaccination in the seniors themselves was not significantly associated with P&I in seniors. CONCLUSION Vaccination of children against influenza may induce herd immunity against influenza for seniors and has the potential to be more beneficial to seniors than the existing policy to prevent influenza by vaccinating seniors themselves. PMID:21275932
Parrish, Amanda T; Graves, Meredith C; Harris, Jeffrey R; Hannon, Peggy A; Hammerback, Kristen; Allen, Claire L
Restaurant employees represent a substantial portion of the US workforce, interact closely with the public, and are at risk for contracting influenza, yet their influenza vaccination rates and attitudes are unknown. Assess influenza vaccination rates and attitudes among Seattle restaurant employees, to identify factors that could enhance the success of a restaurant-based vaccination program. In 2012, we invited employees of Seattle restaurants to complete an anonymous paper survey assessing participant demographics, previous influenza vaccination status, and personal attitudes toward influenza vaccination (using a 5-point scale). Sit-down, full service restaurants in or near Seattle, Washington, were eligible if they had no previous history of offering worksite influenza vaccinations and had more than 20 employees who were older than 18 years and spoke either English or Spanish. We invited staff in all restaurant positions (servers, bussers, kitchen staff, chefs, managers, etc) to complete the survey, which was available in English and Spanish. Of 428 restaurant employees surveyed, 26% reported receiving the seasonal influenza vaccine in 2011-2012 (response rate = 74%). Across 8 attitude statements, participants were most likely to agree that the vaccine is not too expensive (89%), and least likely to agree that it is relevant for their age group (25%), or normative at their workplace (13%). Vaccinated participants reported significantly more positive attitudes than unvaccinated participants, and Hispanics reported significantly more positive attitudes than non-Hispanic whites. Increasing influenza vaccination rates among restaurant employees could protect a substantial portion of the US workforce, and the public, from influenza. Seattle restaurant employees have low vaccination rates against seasonal influenza. Interventions aimed at increasing vaccination among restaurant employees should highlight the vaccine's relevance and effectiveness for working-age adults.
Full Text Available Live attenuated influenza vaccines (LAIVs are considered as safe and effective tool to control influenza in different age groups, especially in young children. An important part of the LAIV safety evaluation is the detection of vaccine virus replication in the nasopharynx of the vaccinees, with special attention to a potential virus transmission to the unvaccinated close contacts. Conducting LAIV clinical trials in some geographical regions with year-round circulation of influenza viruses warrants the development of robust and reliable tools for differentiating vaccine viruses from wild-type influenza viruses in nasal pharyngeal wash (NPW specimens of vaccinated subjects. Here we report the development of genotyping assay for the detection of wild-type and vaccine-type influenza virus genes in NPW specimens of young children immunized with Russian-backbone seasonal trivalent LAIV using Sanger sequencing from newly designed universal primers. The new primer set allowed amplification and sequencing of short fragments of viral genes in NPW specimens and appeared to be more sensitive than conventional real-time RT-PCR protocols routinely used for the detection and typing/subtyping of influenza virus in humans. Furthermore, the new assay is capable of defining the origin of wild-type influenza virus through BLAST search with the generated sequences of viral genes fragments.
Basurto-Dávila, Ricardo; Meltzer, Martin I; Mills, Dora A; Beeler Asay, Garrett R; Cho, Bo-Hyun; Graitcer, Samuel B; Dube, Nancy L; Thompson, Mark G; Patel, Suchita A; Peasah, Samuel K; Ferdinands, Jill M; Gargiullo, Paul; Messonnier, Mark; Shay, David K
To estimate the societal economic and health impacts of Maine's school-based influenza vaccination (SIV) program during the 2009 A(H1N1) influenza pandemic. Primary and secondary data covering the 2008-09 and 2009-10 influenza seasons. We estimated weekly monovalent influenza vaccine uptake in Maine and 15 other states, using difference-in-difference-in-differences analysis to assess the program's impact on immunization among six age groups. We also developed a health and economic Markov microsimulation model and conducted Monte Carlo sensitivity analysis. We used national survey data to estimate the impact of the SIV program on vaccine coverage. We used primary data and published studies to develop the microsimulation model. The program was associated with higher immunization among children and lower immunization among adults aged 18-49 years and 65 and older. The program prevented 4,600 influenza infections and generated $4.9 million in net economic benefits. Cost savings from lower adult vaccination accounted for 54 percent of the economic gain. Economic benefits were positive in 98 percent of Monte Carlo simulations. SIV may be a cost-beneficial approach to increase immunization during pandemics, but programs should be designed to prevent lower immunization among nontargeted groups. © Health Research and Educational Trust.
Muñoz, M Pilar; Soldevila, Núria; Martínez, Anna; Carmona, Glòria; Batalla, Joan; Acosta, Lesly M; Domínguez, Angela
The objective of this work was to study the behaviour of influenza with respect to morbidity and all-cause mortality in Catalonia, and their association with influenza vaccination coverage. The study was carried out over 13 influenza seasons, from epidemiological week 40 of 1994 to week 20 of 2007, and included confirmed cases of influenza and all-cause mortality. Two generalized linear models were fitted: influenza-associated morbidity was modelled by Poisson regression and all-cause mortality by negative binomial regression. The seasonal component was modelled with the periodic function formed by the sum of the sinus and cosines. Expected influenza mortality during periods of influenza virus circulation was estimated by Poisson regression and its confidence intervals using the Bootstrap approach. Vaccination coverage was associated with a reduction in influenza-associated morbidity (pcase of influenza-associated morbidity, an increase of 5% in vaccination coverage represented a reduction of 3% in the incidence rate of influenza. There was a positive association between influenza-associated morbidity and all-cause mortality. Excess mortality attributable to influenza epidemics was estimated as 34.4 (95% CI: 28.4-40.8) weekly deaths. In conclusion, all-cause mortality is a good indicator of influenza surveillance and vaccination coverage is associated with a reduction in influenza-associated morbidity but not with all-cause mortality. Copyright © 2011 Elsevier Ltd. All rights reserved.
Elzinga, Sarah; Reedy, Stephanie; Barker, Virginia D; Chambers, Thomas M; Adams, Amanda A
Obesity is an increasing problem in the equine population with recent reports indicating that the percentage of overweight horses may range anywhere from 20.6-51%. Obesity in horses has been linked to more serious health concerns such as equine metabolic syndrome (EMS). EMS is a serious problem in the equine industry given its defining characteristics of insulin dysregualtion and obesity, as well as the involvement of laminitis. Little research however has been conducted to determine the effects of EMS on routine healthcare of these horses, in particular how they respond to vaccination. It has been shown that obese humans and mice have decreased immune responses to vaccination. EMS may have similar effects on vaccine responses in horses. If this is the case, these animals may be more susceptible to disease, acting as unknown disease reservoirs. Therefore, we investigated the effects of EMS on immune responses to routine influenza vaccination. Twenty-five adult horses of mixed-sex and mixed-breed (8-21 years old) horses; 13 EMS and 12 non-EMS were selected. Within each group, 4 horses served as non-vaccinate saline controls and the remaining horses were vaccinated with a commercially available equine influenza vaccine. Vaccination (influenza or saline) was administered on weeks 0 and 3, and peripheral blood samples taken on week 0 prior to vaccination and on weeks 1, 2, 3, 4, and 5 post vaccination. Blood samples were used to measure hemagglutination inhibition (HI) titers and equine influenza specific IgGa, IgGb, and IgGT levels. Blood samples were also used to isolate peripheral blood mononuclear cells (PBMCs) for analysis of cell mediated immune (CMI) responses via real-time polymerase chain reaction (RT-PCR). All horses receiving influenza vaccination responded with significant increases (P equine influenza specific antibodies following vaccination compared to saline controls. EMS did not significantly affect (P > 0.05) humoral immune responses as measured
Raymond, Donald D.; Bajic, Goran; Ferdman, Jack; Suphaphiphat, Pirada; Settembre, Ethan C.; Moody, M. Anthony; Schmidt, Aaron G.; Harrison, Stephen C. (Duke-MED); (CH-Boston); (Seqirus)
Antigenic variation requires frequent revision of annual influenza vaccines. Next-generation vaccine design strategies aim to elicit a broader immunity by directing the human immune response toward conserved sites on the principal viral surface protein, the hemagglutinin (HA). We describe a group of antibodies that recognize a hitherto unappreciated, conserved site on the HA of H1 subtype influenza viruses. Mutations in that site, which required a change in the H1 component of the 2017 vaccine, had not previously “taken over” among circulating H1 viruses. Our results encourage vaccine design strategies that resurface a protein to focus the immune response on a specific region.
Merani, Shahzma; Kuchel, George A; Kleppinger, Alison; McElhaney, Janet E
Age-related changes in T-cell function are associated with a loss of influenza vaccine efficacy in older adults. Both antibody and cell-mediated immunity plays a prominent role in protecting older adults, particularly against the serious complications of influenza. High dose (HD) influenza vaccines induce higher antibody titers in older adults compared to standard dose (SD) vaccines, yet its impact on T-cell memory is not clear. The aim of this study was to compare the antibody and T-cell responses in older adults randomized to receive HD or SD influenza vaccine as well as determine whether cytomegalovirus (CMV) serostatus affects the response to vaccination, and identify differences in the response to vaccination in those older adults who subsequently have an influenza infection. Older adults (≥65years) were enrolled (n=106) and randomized to receive SD or HD influenza vaccine. Blood was collected pre-vaccination, followed by 4, 10 and 20weeks post-vaccination. Serum antibody titers, as well as levels of inducible granzyme B (iGrB) and cytokines were measured in PBMCs challenged ex vivo with live influenza virus. Surveillance conducted during the influenza season identified those with laboratory confirmed influenza illness or infection. HD influenza vaccination induced a high antibody titer and IL-10 response, and a short-lived increase in Th1 responses (IFN-γ and iGrB) compared to SD vaccination in PBMCs challenged ex vivo with live influenza virus. Of the older adults who became infected with influenza, a high IL-10 and iGrB response in virus-challenged cells was observed post-infection (week 10 to 20), as well as IFN-γ and TNF-α at week 20. Additionally, CMV seropositive older adults had an impaired iGrB response to influenza virus-challenge, regardless of vaccine dose. This study illustrates that HD influenza vaccines have little impact on the development of functional T-cell memory in older adults. Furthermore, poor outcomes of influenza infection in
Clegg, Christopher H; Roque, Richard; Van Hoeven, Neal; Perrone, Lucy; Baldwin, Susan L; Rininger, Joseph A; Bowen, Richard A; Reed, Steven G
Extensive preparation is underway to mitigate the next pandemic influenza outbreak. New vaccine technologies intended to supplant egg-based production methods are being developed, with recombinant hemagglutinin (rHA) as the most advanced program for preventing seasonal and avian H5N1 Influenza. Increased efforts are being focused on adjuvants that can broaden vaccine immunogenicity against emerging viruses and maximize vaccine supply on a worldwide scale. Here, we test protection against avian flu by using H5N1-derived rHA and GLA-SE, a two-part adjuvant system containing glucopyranosyl lipid adjuvant (GLA), a formulated synthetic Toll-like receptor 4 agonist, and a stable emulsion (SE) of oil in water, which is similar to the best-in-class adjuvants being developed for pandemic flu. Notably, a single submicrogram dose of rH5 adjuvanted with GLA-SE protects mice and ferrets against a high titer challenge with H5N1 virus. GLA-SE, relative to emulsion alone, accelerated induction of the primary immune response and broadened its durability against heterosubtypic H5N1 virus challenge. Mechanistically, GLA-SE augments protection via induction of a Th1-mediated antibody response. Innate signaling pathways that amplify priming of Th1 CD4 T cells will likely improve vaccine performance against future outbreaks of lethal pandemic flu.
Berman, Pamela Protzel; Orenstein, Walter A; Hinman, Alan R; Gazmararian, Julie
There is growing interest in simplifying recommendations to vaccinate Americans against influenza. The article discusses interviews with 35 stakeholders from the medical, public health, educational, insurance, and vaccine industry sectors to assess the potential for policy change, and discusses questions posed to the interviewees on current and future influenza vaccination policy and barriers to policy change. About 97% of respondents support the expansion of vaccination for all school-age children, and about 95% support universal vaccination, but there are reservations expressed by the respondents, despite the support for this policy change. Barriers to influenza vaccination recommendations include access, supply, confusing recommendations, and public perceptions. Barriers to universal vaccination include lack of infrastructure, cost, need for education, and vaccine supply. Issues concerning resources and education are challenges that impede policy change. The study findings can be useful to policy makers and practitioners for reviewing U.S. vaccination policy and changes to the policy.
Wielink, van R.
Vaccination of poultry can be used as a tool to control outbreaks of avian influenza, including that of highly pathogenic H5 and H7 strains. Influenza vaccines are traditionally produced in embryonated chicken eggs. Continuous cell lines have been suggested as an alternative substrate to produce
Full Text Available The emergence of a highly pathogenic avian influenza virus H5N1 has increased the potential for a new pandemic to occur. This event highlights the necessity for developing a new generation of influenza vaccines to counteract influenza disease. These vaccines must be manufactured for mass immunization of humans in a timely manner. Poultry should be included in this policy, since persistent infected flocks are the major source of avian influenza for human infections. Recombinant adenoviral vectored H5N1 vaccines are an attractive alternative to the currently licensed influenza vaccines. This class of vaccines induces a broadly protective immunity against antigenically distinct H5N1, can be manufactured rapidly, and may allow mass immunization of human and poultry. Recombinant adenoviral vectors derived from both human and non-human adenoviruses are currently being investigated and appear promising both in nonclinical and clinical studies. This review will highlight the current status of various adenoviral vectored H5N1 vaccines and will outline novel approaches for the future.
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 ...
Barret, A S
We conducted a case-control study to estimate the 2010\\/2011 trivalent influenza vaccine effectiveness (TIVE) using the Irish general practitioners\\' influenza sentinel surveillance scheme. Cases were influenza-like illness (ILI) patients with laboratory-confirmed influenza. Controls were ILI patients who tested negative for influenza. Participating sentinel general practitioners (GP) collected swabs from patients presenting with ILI along with their vaccination history and other individual characteristics. The TIVE was computed as (1 - odds ratiofor vaccination) x100%. Of 60 sentinel GP practices, 22 expressed interest in participating in the study and 17 (28%) recruited at least one ILI patient. In the analysis, we included 106 cases and 85 controls. Seven controls (8.2%) and one influenza case (0.9%) had been vaccinated in 2010\\/2011. The estimated TIVE against any influenza subtype was 89.4% [95% CI: 13.8; 99.8%], suggesting a protective effect against GP-attended laboratory confirmed influenza. This study design could be used to monitor influenza vaccine effectiveness annually but sample size and vaccination coverage should be increased to obtain precise and adjusted estimates.
Loeffen, W L A; Stockhofe, N; Weesendorp, E; van Zoelen-Bos, D; Heutink, R; Quak, S; Goovaerts, D; Heldens, J G M; Maas, R; Moormann, R J; Koch, G
In April 2009 a new influenza A/H1N1 strain, currently named "pandemic (H1N1) influenza 2009" (H1N1v), started the first official pandemic in humans since 1968. Several incursions of this virus in pig herds have also been reported from all over the world. Vaccination of pigs may be an option to reduce exposure of human contacts with infected pigs, thereby preventing cross-species transfer, but also to protect pigs themselves, should this virus cause damage in the pig population. Three swine influenza vaccines, two of them commercially available and one experimental, were therefore tested and compared for their efficacy against an H1N1v challenge. One of the commercial vaccines is based on an American classical H1N1 influenza strain, the other is based on a European avian H1N1 influenza strain. The experimental vaccine is based on reassortant virus NYMC X179A (containing the hemagglutinin (HA) and neuraminidase (NA) genes of A/California/7/2009 (H1N1v) and the internal genes of A/Puerto Rico/8/34 (H1N1)). Excretion of infectious virus was reduced by 0.5-3 log(10) by the commercial vaccines, depending on vaccine and sample type. Both vaccines were able to reduce virus replication especially in the lower respiratory tract, with less pathological lesions in vaccinated and subsequently challenged pigs than in unvaccinated controls. In pigs vaccinated with the experimental vaccine, excretion levels of infectious virus in nasal and oropharyngeal swabs, were at or below 1 log(10)TCID(50) per swab and lasted for only 1 or 2 days. An inactivated vaccine containing the HA and NA of an H1N1v is able to protect pigs from an infection with H1N1v, whereas swine influenza vaccines that are currently available are of limited efficaciousness. Whether vaccination of pigs against H1N1v will become opportune remains to be seen and will depend on future evolution of this strain in the pig population. Close monitoring of the pig population, focussing on presence and evolution of
Full Text Available Abstract Background Annual trivalent influenza vaccines (TIV containing three influenza strains (A/H1N1, A/H3N2, and one B have been recommended for the prevention of influenza. However, worldwide co-circulation of two distinct B lineages (Victoria and Yamagata and difficulties in predicting which lineage will predominate each season have led to the development of quadrivalent influenza vaccines (QIV, which include both B lineages. Our analysis evaluates the public health benefit and associated influenza-related costs avoided which would have been obtained by using QIV rather than TIV in Australia over the period 2002–2012. Methods A static model stratified by age group was used, focusing on people at increased risk of influenza as defined by the Australian vaccination recommendations. B-lineage cross-protection was accounted for. We calculated the potential impact of QIV compared with TIV over the seasons 2002–2012 (2009 pandemic year excluded using Australian data on influenza circulation, vaccine coverage, hospitalisation and mortality rates as well as unit costs, and international data on vaccine effectiveness, influenza attack rate, GP consultation rate and working days lost. Third-party payer and societal influenza-related costs were estimated in 2014 Australian dollars. Sensitivity analyses were conducted. Results Using QIV instead of TIV over the period 2002–2012 would have prevented an estimated 68,271 additional influenza cases, 47,537 GP consultations, 3,522 hospitalisations and 683 deaths in the population at risk of influenza. These results translate into influenza-related societal costs avoided of $46.5 million. The estimated impact of QIV was higher for young children and the elderly. The overall impact of QIV depended mainly on vaccine effectiveness and the influenza attack rate attributable to the mismatched B lineage. Conclusion The broader protection offered by QIV would have reduced the number of influenza infections
Naleway, Allison L; Henkle, Emily M; Ball, Sarah; Bozeman, Sam; Gaglani, Manjusha J; Kennedy, Erin D; Thompson, Mark G
Annual influenza vaccination is recommended for health care personnel (HCP). We describe influenza vaccination coverage among HCP during the 2010-2011 season and present reported facilitators of and barriers to vaccination. We enrolled HCP 18 to 65 years of age, working full time, with direct patient contact. Participants completed an Internet-based survey at enrollment and the end of influenza season. In addition to self-reported data, we collected information about the 2010-2011 influenza vaccine from electronic employee health and medical records. Vaccination coverage was 77% (1,307/1,701). Factors associated with higher vaccination coverage include older age, being married or partnered, working as a physician or dentist, prior history of influenza vaccination, more years in patient care, and higher job satisfaction. Personal protection was reported as the most important reason for vaccination followed closely by convenience, protection of patients, and protection of family and friends. Concerns about perceived vaccine safety and effectiveness and low perceived susceptibility to influenza were the most commonly reported barriers to vaccination. About half of the unvaccinated HCP said they would have been vaccinated if required by their employer. Influenza vaccination in this cohort was relatively high but still fell short of the recommended target of 90% coverage for HCP. Addressing concerns about vaccine safety and effectiveness are possible areas for future education or intervention to improve coverage among HCP. Copyright © 2014 Association for Professionals in Infection Control and Epidemiology, Inc. All rights reserved.
Thorrington, Dominic; Jit, Mark; Eames, Ken
The UK commenced an extension to the seasonal influenza vaccination policy in autumn 2014 that will eventually see all healthy children between the ages of 2-16 years offered annual influenza vaccination. Models suggest that the new policy will be both highly effective at reducing the burden of influenza as well as cost-effective. We explore whether targeting vaccination at either primary or secondary schools would be more effective and/or cost-effective than the current strategy. An age-structured deterministic transmission dynamic SEIR-type mathematical model was used to simulate a national influenza outbreak in England. Costs including GP consultations, hospitalisations due to influenza and vaccinations were compared to potential gains in quality-adjusted life years achieved through vaccinating healthy children. Costs and benefits of the new JCVI vaccination policy were estimated over a single season, and compared to the hypothesised new policies of targeted and heterogeneous vaccination. All potential vaccination policies were highly cost-effective. Influenza transmission can be eliminated for a particular season by vaccinating both primary and secondary school children, but not by vaccinating only one group. The most cost-effective policy overall is heterogeneous vaccination coverage with 48% uptake in primary schools and 34% in secondary schools. The Joint Committee on Vaccination and Immunisation can consider a modification to their policy of offering seasonal influenza vaccinations to all healthy children of ages 2-16 years. Copyright © 2015 Elsevier Ltd. All rights reserved.
I.A. de Bruijn (Iris); E.J. Remarque (Edmond); W.E.Ph. Beyer (Walter); S. le Cessie (Saskia); N. Masurel (Nic); G.L. Ligthart (Gerard)
textabstractThe benefit of annually repeated influenza vaccination on antibody formation is still under debate. In this study the effect of annually repeated influenza vaccination on haemagglutination inhibiting (HI) antibody formation in the elderly is investigated. Between 1990 and 1993 healthy
Malik Peiris, J S
Past pandemics arose from low pathogenic avian influenza (LPAI) viruses. In more recent times, highly pathogenic avian influenza (HPAI) H5N1, LPAI H9N2 and both HPAI and LPAI H7 viruses have repeatedly caused zoonotic disease in humans. Such infections did not lead to sustained human-to-human transmission. Experimental infection of human volunteers and seroepidemiological studies suggest that avian influenza viruses of other subtypes may also infect humans. Viruses of the H7 subtype appear to have a predilection to cause conjunctivitis and influenza-like illness (ILI), although HPAI H7N7 virus has also caused fatal respiratory disease. Low pathogenic H9N2 viruses have caused mild ILI and its occurrence may be under-recognised for this reason. In contrast, contemporary HPAI H5N1 viruses are exceptional in their virulence for humans and differ from human seasonal influenza viruses in their pathogenesis. Patients have a primary viral pneumonia progressing to acute respiratory distress syndrome (ARDS) and multiple organ dysfunction syndrome. Over 380 human cases have been confirmed to date, with an overall case fatality of 63%. The zoonotic transmission of avian influenza is a rare occurrence, butthe greater public health concern is the adaptation of such viruses to efficient human transmission, which could lead to a pandemic. A better understanding of the ecology of avian influenza viruses and the biological determinants of transmissibility and pathogenicity in humans is important for pandemic preparedness.
Barington, T; Juul, Lars; Gyhrs, A
The influence of preexisting immunity on the heavy-chain isotypes of circulating antibody-secreting cells (AbSC) induced by vaccination with Haemophilus influenzae type b (Hib) capsular polysaccharide (HibCP) coupled to tetanus toxoid (TT) or diphtheria toxoid (DT) and by vaccination with TT or D...... of natural HibCP antibodies (r = 0.59; P = 0.00002). A possible role of natural exposure for Hib or cross-reactive bacteria on the mucosal surfaces in the shaping of the isotype response to HibCP conjugate vaccines is discussed....
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. Copyright © 2016 Elsevier Ltd. All rights reserved.
Restrepo Escobar, Mauricio
Full Text Available Vasculitis can be secondary to various processes, among them infections, malignancies, connective tissue diseases or medications, or primary, generally idiopathic. The reported adverse events after vaccination can be mild and transient or more serious such as autoimmune diseases. Possibly the most frequently described autoimmune phenomena after influenza vaccination are different forms of vasculitis. We report the case of a patient who presented a clinical picture of vasculitis classified as polyarteritis nodosa that began two weeks after receiving the influenza vaccine. After critically reviewing the literature, this would be the first clearly documented case of polyarteritis nodosa associated with vaccination against influenza.
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. Copyright © 2016. Published by Elsevier Ltd.
Duerrwald, Ralf; Schlegel, Michael; Bauer, Katja; Vissiennon, Th?ophile; Wutzler, Peter; Schmidtke, Michaela
Recent epidemiological developments demonstrated that gene segments of swine influenza A viruses can account for antigenic changes as well as reduced drug susceptibility of pandemic influenza A viruses. This raises questions about the efficacy of preventive measures against swine influenza A viruses. Here, the protective effect of vaccination was compared with that of prophylactic Tamiflu® treatment against two Eurasian swine influenza A viruses. 11-week-old pigs were infected by aerosol nebu...
Van Kampen, K. R.; Tang, D. C.
Influenza viruses in nature undergo genetic mutation and reassortment. Three pandemics of avian influenza in man were recorded in the twentieth century. Highly pathogenic avian influenza (HPAI) viruses currently in circulation pose a threat for another world-wide pandemic, if they become transmissible from man to man. Manufacturing protective vaccines using current egg-based technology is often difficult due to the virulence of the virus and its adverse effects on the embryonating egg substrate. New technologies allow the creation of safe and protective pandemic influenza vaccines without the need for egg based substrates. These technologies allow new vaccines to be created in less than one month. Manufacturing is in tissue culture, not eggs. Vaccine can be administered to man non-invasively, without adjuvants, eliciting a rapid and protective immune response. Protective immunity against avian influenza (AI) virus was elicited in chickens by single-dose in ovo vaccination with a replication-competent adenovirus (RCA)-free human adenovirus serotype 5 (Ad5)-derived vector encoding an H5N9 avian influenza virus hemagglutinin. Vaccinated chickens were protected against both H5N1 and H5N2 HPAI virus challenges. Mass-administration of this bird flu vaccine can be streamlined with available robotic in ovo injectors. Vaccination using this vaccine could protect the the largest host reservoir (chickens) and greatly reduce the exposure of man to avian influenza. In addition, Ad5-vectored vaccines can be produced rapidly and the safety margin of a non-replicating vector is superior to that of a replicating counterpart. Furthermore, this mode of vaccination is compatible with epidemiological surveys of natural AI virus infections. In addition to mass immunization of poultry, both animals and humans have been effectively immunized by intranasal administration of Ad5-vectored influenza vaccines without any appreciable side effects, even in mice and human volunteers with
Paterson, P; Chantler, T; Larson, HJ
In 2013, the annual influenza immunisation programme in England was extended to children to reduce the burden of influenza, but uptake was sub-optimal at 53.2%. To explore the reasons some parents decided not to vaccinate their child against influenza as part of the pilot programme offered in schools. Cross-sectional qualitative study conducted between February and July 2015. 913 parents whose children were not vaccinated against influenza in the school pilots in West Yorkshire and Greater Ma...
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.
Sexton, Amy; De Rose, Robert; Reece, Jeanette C; Alcantara, Sheilajen; Loh, Liyen; Moffat, Jessica M; Laurie, Karen; Hurt, Aeron; Doherty, Peter C; Turner, Stephen J; Kent, Stephen J; Stambas, John
There is an urgent need for human immunodeficiency virus (HIV) vaccines that induce robust mucosal immunity. Influenza A viruses (both H1N1 and H3N2) were engineered to express simian immunodeficiency virus (SIV) CD8 T-cell epitopes and evaluated following administration to the respiratory tracts of 11 pigtail macaques. Influenza virus was readily detected from respiratory tract secretions, although the infections were asymptomatic. Animals seroconverted to influenza virus and generated CD8 and CD4 T-cell responses to influenza virus proteins. SIV-specific CD8 T-cell responses bearing the mucosal homing marker beta7 integrin were induced by vaccination of naïve animals. Further, SIV-specific CD8 T-cell responses could be boosted by recombinant influenza virus-SIV vaccination of animals with already-established SIV infection. Sequential vaccination with influenza virus-SIV recombinants of different subtypes (H1N1 followed by H3N2 or vice versa) produced only a limited boost in immunity, probably reflecting T-cell immunity to conserved internal proteins of influenza A virus. SIV challenge of macaques vaccinated with an influenza virus expressing a single SIV CD8 T cell resulted in a large anamnestic recall CD8 T-cell response, but immune escape rapidly ensued and there was no impact on chronic SIV viremia. Although our results suggest that influenza virus-HIV vaccines hold promise for the induction of mucosal immunity to HIV, broader antigen cover will be needed to limit cytotoxic T-lymphocyte escape.
First page Back Continue Last page Graphics. Influenza as a human disease. Commonly perceived as a mild disease, affects every one, sometimes a couple of times in a year. Globally, seasonal influenza epidemics result in about three to five million yearly cases of severe illness and about 250,000 to 500,000 yearly ...
... people has ranged from mild to severe. Avian Influenza Transmission Avian Influenza Transmission Infographic [555 KB, 2 pages] Spanish [ ... important for public health. Signs and Symptoms of Avian Influenza A Virus Infections in Humans The reported signs ...
Mina, Michael J.; McCullers, Jonathan A.; Klugman, Keith P.
ABSTRACT Community interactions at mucosal surfaces between viruses, like influenza virus, and respiratory bacterial pathogens are important contributors toward pathogenesis of bacterial disease. What has not been considered is the natural extension of these interactions to live attenuated immunizations, and in particular, live attenuated influenza vaccines (LAIVs). Using a mouse-adapted LAIV against influenza A (H3N2) virus carrying the same mutations as the human FluMist vaccine, we find that LAIV vaccination reverses normal bacterial clearance from the nasopharynx and significantly increases bacterial carriage densities of the clinically important bacterial pathogens Streptococcus pneumoniae (serotypes 19F and 7F) and Staphylococcus aureus (strains Newman and Wright) within the upper respiratory tract of mice. Vaccination with LAIV also resulted in 2- to 5-fold increases in mean durations of bacterial carriage. Furthermore, we show that the increases in carriage density and duration were nearly identical in all aspects to changes in bacterial colonizing dynamics following infection with wild-type (WT) influenza virus. Importantly, LAIV, unlike WT influenza viruses, had no effect on severe bacterial disease or mortality within the lower respiratory tract. Our findings are, to the best of our knowledge, the first to demonstrate that vaccination with a live attenuated viral vaccine can directly modulate colonizing dynamics of important and unrelated human bacterial pathogens, and does so in a manner highly analogous to that seen following wild-type virus infection. PMID:24549845
Childress, Billy-Clyde; Montney, Joshua D; Albro, Elise A
Years ago, intramuscular influenza vaccines were the only option for those who wanted to arm themselves against the flu. Today there are alternatives, including intradermal injections and intranasal sprays. In order to select the right influenza vaccine for their patients, pharmacists, and other healthcare professionals must have a basic understanding of the immune system. Influenza vaccines elicit different levels of immune response involving innate and adaptive immunity, which are critical to fighting infection. For the 2013-2014 flu season, there were 13 different formulations of influenza vaccines on the market with vast differences in indications, contraindications, and effectiveness. The CDC does not recommend one vaccine over another, but recommends that all patients be vaccinated against the flu. Preventing the spread of influenza is no simple task; however, the most recent evidence on influenza vaccines and sufficient knowledge of the immune system will allow pharmacists and other healthcare providers to better advocate for vaccines, determine which are most appropriate, and ensure their proper administration.
Full Text Available To evaluate if, among children aged 3 to 15 years, influenza vaccination for multiple seasons affects the proportion sero-protected.Participants were 131 healthy children aged 3-15 years. Participants were vaccinated with trivalent inactivated seasonal influenza vaccine (TIV over the 2005-06, 2006-07 and 2007-8 seasons. Number of seasons vaccinated were categorized as one (2007-08; two (2007-08 and 2006-07 or 2007-08 and 2005-06 or three (2005-06, 2006-07, and 2007-08. Pre- and post-vaccination sera were collected four weeks apart. Antibody titres were determined by hemagglutination inhibition (HAI assay using antigens to A/Solomon Islands/03/06 (H1N1, A/Wisconsin/67/05 (H3N2 and B/Malaysia/2506/04. The proportions sero-protected were compared by number of seasons vaccinated using cut-points for seroprotection of 1:40 vs. 1:320. The proportions of children sero-protected against H1N1 and H3N2 was high (>85% regardless of number of seasons vaccinated and regardless of cut-point for seroprotection. For B Malaysia there was no change in proportions sero-protected by number of seasons vaccinated; however the proportions protected were lower than for H1N1 and H3N2, and there was a lower proportion sero-protected when the higher, compared to lower, cut-point was used for sero-protection.The proportion of children sero-protected is not affected by number of seasons vaccinated.
Paterson, Pauline; Chantler, Tracey; Larson, Heidi J
In 2013, the annual influenza immunisation programme in England was extended to children to reduce the burden of influenza, but uptake was sub-optimal at 53.2%. To explore the reasons some parents decided not to vaccinate their child against influenza as part of the pilot programme offered in schools. Cross-sectional qualitative study conducted between February and July 2015. 913 parents whose children were not vaccinated against influenza in the school pilots in West Yorkshire and Greater Manchester, England, were asked to comment on their reasons for non-vaccination and invited to take part in a semi-structured interview. 138 parents returned response forms, of which 38 were eligible and interested in participating and 25 were interviewed. Interview transcripts were coded by theme in NVivo. A third of parents who returned response forms had either vaccinated their child elsewhere, intended to have them vaccinated, or had not vaccinated them due to medical reasons (valid or perceived). Most interviewees were not convinced of the need to vaccinate their child against influenza. Parents expressed concerns about influenza vaccine effectiveness and vaccine side effects. Several parents interviewed declined the vaccine for faith reasons due to the presence of porcine gelatine in the vaccine. To significantly decrease the burden of influenza in England, influenza vaccination coverage in children needs to be >60%. Hence, it is important to understand the reasons why parents are not vaccinating their children, and to tailor the communication and immunisation programme accordingly. Our finding that a third of parents, who did not consent to their child being vaccinated as part of the school programme, had actually vaccinated their child elsewhere, intended to have their child vaccinated, or had not vaccinated them due to medical reasons, illustrates the importance of including additional questions or data sources when investigating under-vaccination. Copyright © 2017 The
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.
Full Text Available 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.
Chen, D; Periwal, S B; Larrivee, K; Zuleger, C; Erickson, C A; Endres, R L; Payne, L G
Both circulating and mucosal antibodies are considered important for protection against infection by influenza virus in humans and animals. However, current inactivated vaccines administered by intramuscular injection using a syringe and needle elicit primarily circulating antibodies. In this study, we report that epidermal powder immunization (EPI) via a unique powder delivery system elicits both serum and mucosal antibodies to an inactivated influenza virus vaccine. Serum antibody responses to influenza vaccine following EPI were enhanced by codelivery of cholera toxin (CT), a synthetic oligodeoxynucleotide containing immunostimulatory CpG motifs (CpG DNA), or the combination of these two adjuvants. In addition, secretory immunoglobulin A (sIgA) antibodies were detected in the saliva and mucosal lavages of the small intestine, trachea, and vaginal tract, although the titers were much lower than the IgG titers. The local origin of the sIgA antibodies was further shown by measuring antibodies released from cultured tracheal and small intestinal fragments and by detecting antigen-specific IgA-secreting cells in the lamina propria using ELISPOT assays. EPI with a single dose of influenza vaccine containing CT or CT and CpG DNA conferred complete protection against lethal challenges with an influenza virus isolated 30 years ago, whereas a prime and boost immunizations were required for protection in the absence of an adjuvant. The ability to elicit augmented circulating antibody and mucosal antibody responses makes EPI a promising alternative to needle injection for administering vaccines against influenza and other diseases.
Full Text Available Background. Influenza is a severe respiratory disease caused by influenza virus. According to estimates from the World Health Organisation (WHO, 5–15% of the world’s population, or 330–1575 million people, suffer from influenza each year. The vaccination of patients and health professionals plays an important role in the prevention of infections. Objectives. To describe family doctors’ opinions and behavior concerning influenza vaccination. Material and methods. An online survey was filled out by 77 family physicians, of whom women accounted for 53.5%. The age mean of the doctors surveyed was 44.6 ± 11.7 years. The questionnaire contained 14 questions. Results. 63.6% (49 people of the respondents were worried about flu, and 84.4% (65 people were concerned about the possibility of their family members being infected. 77.9% (60 people approve of vaccination. 51.5% (40 people of the doctors received the vaccination in the current (2015/2016 influenza season. 18.2% (14 of the respondents were vaccinated within the last five seasons. The respondents recommended vaccination against influenza to their families sometimes (50.6%, 39 or frequently (41.6%, 32. They recommended the vaccination to their patients frequently (41.6%, 32 or sometimes (53.2%, 41. Only 18.2% (14 of the respondents were covered by the free vaccination program in their workplace. As many as 76.6% (59 of the doctors would recommend the vaccination more often if it were free, and 44.2% (32 would be more willing to recommend the vaccination if they received additional payment for it. When doctors were asked why they thought patients did not have themselves vaccinated, the reasons most frequently given were: patients’ lack of time and awareness of the disease consequences and complications (57.1%, 44, patients’ fear of postvaccination reactions (44.2%, 34, inconvenience associated with vaccination, including the cost of the vaccine (42.9%, 33, patients’ belief that
Christenson, Brith; Pauksen, Karlis; Sylvan, Staffan P E
The present prospective study was conducted from 2003-2005, among all individuals 65 years and older in Uppsala County, a region with 300 000 inhabitants situated close to the Stockholm urban area.The objective of this study was to assess the preventive effect of influenza and pneumococcal vaccination in reducing hospitalisation and length of hospital stay (LOHS) even during periods of low influenza activity. The specificity of the apparent vaccine associations were evaluated in relation to the influenza seasons. In 2003, the total study population was 41,059, of which 12,907 (31%) received influenza vaccine of these, 4,447 (11%) were administered the pneumococcal vaccine. In 2004, 14,799 (34%) individuals received the influenza vaccine and 8,843 (21%) the pneumococcal vaccine and in 2005 16,926 (39%) individuals were given the influenza vaccine and 12,340 (28%) the pneumococcal vaccine.Our findings indicated that 35% of the vaccinated cohort belonged to a medical risk category (mainly those persons that received the pneumococcal vaccine). Data on hospitalisation and mortality during the 3-year period were obtained from the administrative database of the Uppsala county council. During the influenza seasons, reduction of hospital admissions and significantly shorter in-hospital stay for influenza was observed in the vaccinated cohort (below 80 years of age). For individuals who also had received the pneumococcal vaccine, a significant reduction of hospital admissions and of in-hospital stay was observed for invasive pneumococcal disease and for pneumococcal pneumonia. Effectiveness was observed for cardiac failure even in persons that also had received the pneumococcal vaccine, despite that the pneumococcal vaccinated mainly belonged to a medical risk category. Reduction of death from all causes was observed during the influenza season of 2004, in the 75-84-year old age group and in all age-groups during the influenza season 2005. The present study confirmed the
Sylvan Staffan PE
Full Text Available Abstract Background The present prospective study was conducted from 2003–2005, among all individuals 65 years and older in Uppsala County, a region with 300 000 inhabitants situated close to the Stockholm urban area. The objective of this study was to assess the preventive effect of influenza and pneumococcal vaccination in reducing hospitalisation and length of hospital stay (LOHS even during periods of low influenza activity. The specificity of the apparent vaccine associations were evaluated in relation to the influenza seasons. Results In 2003, the total study population was 41,059, of which 12,907 (31% received influenza vaccine of these, 4,447 (11% were administered the pneumococcal vaccine. In 2004, 14,799 (34% individuals received the influenza vaccine and 8,843 (21% the pneumococcal vaccine and in 2005 16,926 (39% individuals were given the influenza vaccine and 12,340 (28% the pneumococcal vaccine. Our findings indicated that 35% of the vaccinated cohort belonged to a medical risk category (mainly those persons that received the pneumococcal vaccine. Data on hospitalisation and mortality during the 3-year period were obtained from the administrative database of the Uppsala county council. During the influenza seasons, reduction of hospital admissions and significantly shorter in-hospital stay for influenza was observed in the vaccinated cohort (below 80 years of age. For individuals who also had received the pneumococcal vaccine, a significant reduction of hospital admissions and of in-hospital stay was observed for invasive pneumococcal disease and for pneumococcal pneumonia. Effectiveness was observed for cardiac failure even in persons that also had received the pneumococcal vaccine, despite that the pneumococcal vaccinated mainly belonged to a medical risk category. Reduction of death from all causes was observed during the influenza season of 2004, in the 75–84-year old age group and in all age-groups during the influenza
Scherließ, Regina; Ajmera, Ankur; Dennis, Mike; Carroll, Miles W; Altrichter, Jens; Silman, Nigel J; Scholz, Martin; Kemter, Kristina; Marriott, Anthony C
Currently, the need for cooled storage and the impossibility of terminal sterilisation are major drawbacks in vaccine manufacturing and distribution. To overcome current restrictions a preclinical safety and efficacy study was conducted to evaluate new influenza A vaccine formulations regarding thermal resistance, resistance against irradiation-mediated damage and storage stability. We evaluated the efficacy of novel antigen stabilizing and protecting solutions (SPS) to protect influenza A(H1N1)pdm09 split virus antigen under experimental conditions in vitro and in vivo. Original or SPS re-buffered vaccine (Pandemrix) was spray-dried and terminally sterilised by irradiation with 25 kGy (e-beam). Antigen integrity was monitored by SDS-PAGE, dynamic light scattering, size exclusion chromatography and functional haemagglutination assays. In vitro screening experiments revealed a number of highly stable compositions containing glycyrrhizinic acid (GA) and/or chitosan. The most stable composition was selected for storage tests and in vivo assessment of seroconversion in non-human primates (Macaca fascicularis) using a prime-boost strategy. Redispersed formulations with original adjuvant were administered intramuscularly. Storage data revealed high stability of protected vaccines at 4°C and 25°C, 60% relative humidity, for at least three months. Animals receiving original Pandemrix exhibited expected levels of seroconversion after 21 days (prime) and 48 days (boost) as assessed by haemagglutination inhibition and microneutralisation assays. Animals vaccinated with spray-dried and irradiated Pandemrix failed to exhibit seroconversion after 21 days whereas spray-dried and irradiated, SPS-protected vaccines elicited similar seroconversion levels to those vaccinated with original Pandemrix. Boost immunisation with SPS-protected vaccine resulted in a strong increase in seroconversion but had only minor effects in animals treated with non SPS-protected vaccine. In conclusion
Full Text Available There is some evidence that annual vaccination of trivalent inactivated influenza vaccine (TIV may lead to reduced vaccine immunogenicity but evidence is lacking on whether vaccine efficacy is affected by prior vaccination history. The efficacy of one dose of TIV in children 6-8 y of age against influenza B is uncertain. We examined whether immunogenicity and efficacy of influenza vaccination in school-age children varied by age and past vaccination history.We conducted a randomized controlled trial of 2009-10 TIV. Influenza vaccination history in the two preceding years was recorded. Immunogenicity was assessed by comparison of HI titers before and one month after receipt of TIV/placebo. Subjects were followed up for 11 months with symptom diaries, and respiratory specimens were collected during acute respiratory illnesses to permit confirmation of influenza virus infections. We found that previous vaccination was associated with reduced antibody responses to TIV against seasonal A(H1N1 and A(H3N2 particularly in children 9-17 y of age, but increased antibody responses to the same lineage of influenza B virus in children 6-8 y of age. Serological responses to the influenza A vaccine viruses were high regardless of vaccination history. One dose of TIV appeared to be efficacious against confirmed influenza B in children 6-8 y of age regardless of vaccination history.Prior vaccination was associated with lower antibody titer rises following vaccination against seasonal influenza A vaccine viruses, but higher responses to influenza B among individuals primed with viruses from the same lineage in preceding years. In a year in which influenza B virus predominated, no impact of prior vaccination history was observed on vaccine efficacy against influenza B. The strains that circulated in the year of study did not allow us to study the effect of prior vaccination on vaccine efficacy against influenza A.
Jackson, Michael L; Nelson, Jennifer C
The test-negative design has emerged in recent years as the preferred method for estimating influenza vaccine effectiveness (VE) in observational studies. However, the methodologic basis of this design has not been formally developed. In this paper we develop the rationale and underlying assumptions of the test-negative study. Under the test-negative design for influenza VE, study subjects are all persons who seek care for an acute respiratory illness (ARI). All subjects are tested for influenza infection. Influenza VE is estimated from the ratio of the odds of vaccination among subjects testing positive for influenza to the odds of vaccination among subjects testing negative. With the assumptions that (a) the distribution of non-influenza causes of ARI does not vary by influenza vaccination status, and (b) VE does not vary by health care-seeking behavior, the VE estimate from the sample can generalized to the full source population that gave rise to the study sample. Based on our derivation of this design, we show that test-negative studies of influenza VE can produce biased VE estimates if they include persons seeking care for ARI when influenza is not circulating or do not adjust for calendar time. The test-negative design is less susceptible to bias due to misclassification of infection and to confounding by health care-seeking behavior, relative to traditional case-control or cohort studies. The cost of the test-negative design is the additional, difficult-to-test assumptions that incidence of non-influenza respiratory infections is similar between vaccinated and unvaccinated groups within any stratum of care-seeking behavior, and that influenza VE does not vary across care-seeking strata. Copyright © 2013 Elsevier Ltd. All rights reserved.
Efficacy and safety of vaccine «Grippol» among children with different health status was analyzed. The most efficacy of the influenza vaccine revealed in the group of children with compromised health status, as well as in the group of allergic children. The safety of influenza vaccination was confirmed in children with different health conditions.Key words: children, vaccination, influenza, efficacy, safety.
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.…
Patel, Rajan; Longini, Ira M; Halloran, M Elizabeth
In the event of pandemic influenza, only limited supplies of vaccine may be available. We use stochastic epidemic simulations, genetic algorithms (GA), and random mutation hill climbing (RMHC) to find optimal vaccine distributions to minimize the number of illnesses or deaths in the population, given limited quantities of vaccine. Due to the non-linearity, complexity and stochasticity of the epidemic process, it is not possible to solve for optimal vaccine distributions mathematically. However, we use GA and RMHC to find near optimal vaccine distributions. We model an influenza pandemic that has age-specific illness attack rates similar to the Asian pandemic in 1957-1958 caused by influenza A(H2N2), as well as a distribution similar to the Hong Kong pandemic in 1968-1969 caused by influenza A(H3N2). We find the optimal vaccine distributions given that the number of doses is limited over the range of 10-90% of the population. While GA and RMHC work well in finding optimal vaccine distributions, GA is significantly more efficient than RMHC. We show that the optimal vaccine distribution found by GA and RMHC is up to 84% more effective than random mass vaccination in the mid range of vaccine availability. GA is generalizable to the optimization of stochastic model parameters for other infectious diseases and population structures.
E.G. Wijnans (Leonoor)
markdownabstractIn 2009 and 2010 the world experienced the first influenza pandemic of the 21st century. As the new influenza A(H1N1)pdm09 virus spread across the world, vaccines were being produced and licensed at an unprecedented scale and speed. In Europe, adjuvanted and non-adjuvanted H1N1pdm09
Postma, Maarten J.; Bos, Jasper M.; Van Gennep, Mark; Jager, Johannes C.; Baltussen, Rob; Sprenger, Marc J.W.
Objective: The objective of this study was to determine the costs associated with influenza and the cost effectiveness (net costs per life-year gained) of influenza vaccination in The Netherlands. Design and setting: The economic evaluation comprised a cost-of-illness assessment and a
Here we provide recommendations for the use of viral vaccines in anticipation of the 2014 southern hemisphere influenza season. For a review of the 2013 influenza season, please refer to the National Institute for Communicable Diseases, National Health Laboratory Service website (http://www.nicd.ac.za).
Ivanov, A.A.; Ershov, F.I.; Ulanova, A.M.; Kuz'mina, T.D.; Stavrakova, N.M.; Tazulakhova, Eh.B.; Shal'nova, G.A.; Akademiya Meditsinskikh Nauk SSSR, Moscow
Different methods of prophylactic treatment with influenza virus vaccina increase survival of irradiated mice and hamsters by 25-55% as compared to unprotected ones. Higher radioresistance occurs in the same time intervals as a rise of interferon in the blood after immunization with influenza virus vaccine. 7 refs.; 2 figs.; 2 tabs
Ali Tahsin Gunes
Full Text Available Psoriasis is a chronic, recurrent, immune-mediated inflammatory disease and it can be provoked or exacerbated by a variety of different environmental factors, particularly infections and drugs. In addition, a possible association between vaccination and the new onset and/or exacerbation of psoriasis has been reported by a number of different authors. The aim of this study is to investigate the effects of influenza vaccination on patients with psoriasis. Here, we report the findings from 43 patients suffering from psoriasis (clinical phenotypes as mixed guttate/plaque lesions, palmoplantar or scalp psoriasis whose diseases had been triggered after influenza vaccination applied in the 2009-2010 season. The short time intervals between vaccination and psoriasis flares in our patients and the lack of other possible triggers suggest that influenza vaccinations may have provocative effects on psoriasis. However, further large and controlled studies need to be carried out to confirm this relationship.
Koutsonanos, Dimitrios G; Esser, E Stein; McMaster, Sean R; Kalluri, Priya; Lee, Jeong-Woo; Prausnitz, Mark R; Skountzou, Ioanna; Denning, Timothy L; Kohlmeier, Jacob E; Compans, Richard W
Skin has gained substantial attention as a vaccine target organ due to its immunological properties, which include a high density of professional antigen presenting cells (APCs). Previous studies have demonstrated the effectiveness of this vaccination route not only in animal models but also in adults. Young children represent a population group that is at high risk from influenza infection. As a result, this group could benefit significantly from influenza vaccine delivery approaches through the skin and the improved immune response it can induce. In this study, we compared the immune responses in young BALB/c mice upon skin delivery of influenza vaccine with vaccination by the conventional intramuscular route. Young mice that received 5 μg of H1N1 A/Ca/07/09 influenza subunit vaccine using MN demonstrated an improved serum antibody response (IgG1 and IgG2a) when compared to the young IM group, accompanied by higher numbers of influenza-specific antibody secreting cells (ASCs) in the bone marrow. In addition, we observed increased activation of follicular helper T cells and formation of germinal centers in the regional lymph nodes in the MN immunized group, rapid clearance of the virus from their lungs as well as complete survival, compared with partial protection observed in the IM-vaccinated group. Our results support the hypothesis that influenza vaccine delivery through the skin would be beneficial for protecting the high-risk young population from influenza infection. Copyright © 2015. Published by Elsevier Ltd.
Background Influenza vaccination in infants and children with existing health complications is current practice in many countries, but healthy children are also susceptible to influenza, sometimes with complications. The under-recognised burden of disease in young children is greater than in elderly populations and the number of paediatric influenza cases reported does not reflect the actual frequency of influenza. Discussion Vaccination of healthy children is not widespread in Europe despite clear demonstration of the benefits of vaccination in reducing the large health and economic burden of influenza. Universal vaccination of infants and children also provides indirect protection in other high-risk groups in the community. This paper contains the Central European Vaccination Advisory Group (CEVAG) guidance statement on recommendations for the vaccination of infants and children against influenza. The aim of CEVAG is to encourage the efficient and safe use of vaccines to prevent and control infectious diseases. Summary CEVAG recommends the introduction of universal influenza vaccination for all children from the age of 6 months. Special attention is needed for children up to 60 months of age as they are at greatest risk. Individual countries should decide on how best to implement this recommendation based on their circumstances. PMID:20546586
Barington, T; Kristensen, K; Henrichsen, J
of Haemophilus influenzae type b capsular polysaccharide (PRP) and diphtheria toxoid (DT), and the response was related to the prevaccination levels of PRP and DT antibodies. Positive correlations were found between increases in plasma PRP (median, 32.0 micrograms/ml) and DT (1.14 IU/ml) antibodies and numbers...
Carville, Kylie S; Grant, Kristina A; Sullivan, Sheena G; Fielding, James E; Lane, Courtney R; Franklin, Lucinda; Druce, Julian; Kelly, Heath A
The influenza virus undergoes frequent antigenic drift, necessitating annual review of the composition of the influenza vaccine. Vaccination is an important strategy for reducing the impact and burden of influenza, and estimating vaccine effectiveness (VE) each year informs surveillance and preventative measures. We aimed to describe the influenza season and to estimate the effectiveness of the influenza vaccine in Victoria, Australia, in 2013. Routine laboratory notifications, general practitioner sentinel surveillance (including a medical deputising service) data, and sentinel hospital admission surveillance data for the influenza season (29 April to 27 October 2013) were collated in Victoria, Australia, to describe influenza-like illness or confirmed influenza during the season. General practitioner sentinel surveillance data were used to estimate VE against medically-attended laboratory confirmed influenza. VE was estimated using the case test negative design as 1-adjusted odds ratio (odds of vaccination in cases compared with controls) × 100%. Cases tested positive for influenza while non-cases (controls) tested negative. Estimates were adjusted for age group, week of onset, time to swabbing and co-morbidities. The 2013 influenza season was characterised by relatively low activity with a late peak. Influenza B circulation preceded that of influenza A(H1)pdm09, with very little influenza A(H3) circulation. Adjusted VE for all influenza was 55% (95%CI: -11, 82), for influenza A(H1)pdm09 was 43% (95%CI: -132, 86), and for influenza B was 56% (95%CI: -51, 87) Imputation of missing data raised the influenza VE point estimate to 64% (95%CI: 13, 85). Clinicians can continue to promote a positive approach to influenza vaccination, understanding that inactivated influenza vaccines prevent at least 50% of laboratory-confirmed outcomes in hospitals and the community. Copyright © 2014 Elsevier Ltd. All rights reserved.
Full Text Available BACKGROUND: Southeast Asia is a region with great potential for the emergence of a pandemic influenza virus. Global efforts to improve influenza surveillance in this region have documented the burden and seasonality of influenza viruses and have informed influenza prevention strategies, but little information exists about influenza vaccination guidelines and vaccine sales. METHODS: To ascertain the existence of influenza vaccine guidelines and define the scope of vaccine sales, we sent a standard three-page questionnaire to the ten member nations of the Association of Southeast Asian Nations. We also surveyed three multinational manufacturers who supply influenza vaccines in the region. RESULTS: Vaccine sales in the private sector were <1000 per 100,000 population in the 10 countries. Five countries reported purchasing vaccine for use in the public sector. In 2011, Thailand had the highest combined reported rate of vaccine sales (10,333 per 100,000. In the 10 countries combined, the rate of private sector sales during 2010-2011 (after the A(H1N12009pdm pandemic exceeded 2008 pre-pandemic levels. Five countries (Indonesia, Malaysia, Singapore, Thailand and Vietnam had guidelines for influenza vaccination but only two were consistent with global guidelines. Four recommended vaccination for health care workers, four for elderly persons, three for young children, three for persons with underlying disease, and two for pregnant women. CONCLUSIONS: The rate of vaccine sales in Southeast Asia remains low, but there was a positive impact in sales after the A(H1N12009pdm pandemic. Low adherence to global vaccine guidelines suggests that more work is needed in the policy arena.
Holst, Peter Johannes; Christensen, Jan Pravsgaard; Thomsen, Allan Randrup
We may expect that the next influenza pandemic will affect about half the world's population within a year and that it will cause unpredictable mortality rates. In this perspective, we review the molecular mechanisms underlying the development of new pandemic influenza strains and a discussion...... on existing and future vaccination strategies directed towards prevention of pandemic influenza is presented. There is an urgent need to develop paninfluenza-specific vaccines and invest substantially in new technologies in order to better meet this threat. Udgivelsesdato: 2008-Nov-24...
Chad R Wells
Full Text Available Theoretical models of infection spread on networks predict that targeting vaccination at individuals with a very large number of contacts (superspreaders can reduce infection incidence by a significant margin. These models generally assume that superspreaders will always agree to be vaccinated. Hence, they cannot capture unintended consequences such as policy resistance, where the behavioral response induced by a new vaccine policy tends to reduce the expected benefits of the policy. Here, we couple a model of influenza transmission on an empirically-based contact network with a psychologically structured model of influenza vaccinating behavior, where individual vaccinating decisions depend on social learning and past experiences of perceived infections, vaccine complications and vaccine failures. We find that policy resistance almost completely undermines the effectiveness of superspreader strategies: the most commonly explored approaches that target a randomly chosen neighbor of an individual, or that preferentially choose neighbors with many contacts, provide at best a 2% relative improvement over their non-targeted counterpart as compared to 12% when behavioral feedbacks are ignored. Increased vaccine coverage in super spreaders is offset by decreased coverage in non-superspreaders, and superspreaders also have a higher rate of perceived vaccine failures on account of being infected more often. Including incentives for vaccination provides modest improvements in outcomes. We conclude that the design of influenza vaccine strategies involving widespread incentive use and/or targeting of superspreaders should account for policy resistance, and mitigate it whenever possible.
Full Text Available The article considers the results of infantile mass vaccination with inactivated subunit influenza vaccine (Influvac. It shows that vaccination of 57–72% of children aged 3–17 from organized collectives residing in Mytishchi and Orekhovoczuevo districts of Moscow region was accompanied with nearly triple reduce of flu rates vs. Narofominsk and Odintsovo districts where vaccination was occasional (< 1% of children. The efficiency of the vaccination made 63,7%. Low reactogenicity of the influenza vaccine was recorded. Its convenient packing allows vaccination of large number of children in a short time. The article justifies the necessity of yearly vaccinations even in case of similarity of flu virus strain.Key words: children, mass vaccination, subunit flu vaccine, safety.
E. Bridie Clemens
Full Text Available Next-generation vaccines that utilize T cells could potentially overcome the limitations of current influenza vaccines that rely on antibodies to provide narrow subtype-specific protection and are prone to antigenic mismatch with circulating strains. Evidence from animal models shows that T cells can provide heterosubtypic protection and are crucial for immune control of influenza virus infections. This has provided hope for the design of a universal vaccine able to prime against diverse influenza virus strains and subtypes. However, multiple hurdles exist for the realisation of a universal T cell vaccine. Overall primary concerns are: extrapolating human clinical studies, seeding durable effective T cell resident memory (Trm, population human leucocyte antigen (HLA coverage, and the potential for T cell-mediated immune escape. Further comprehensive human clinical data is needed during natural infection to validate the protective role T cells play during infection in the absence of antibodies. Furthermore, fundamental questions still exist regarding the site, longevity and duration, quantity, and phenotype of T cells needed for optimal protection. Standardised experimental methods, and eventually simplified commercial assays, to assess peripheral influenza-specific T cell responses are needed for larger-scale clinical studies of T cells as a correlate of protection against influenza infection. The design and implementation of a T cell-inducing vaccine will require a consensus on the level of protection acceptable in the community, which may not provide sterilizing immunity but could protect the individual from severe disease, reduce the length of infection, and potentially reduce transmission in the community. Therefore, increasing the standard of care potentially offered by T cell vaccines should be considered in the context of pandemic preparedness and zoonotic infections, and in combination with improved antibody vaccine targeting methods
Ishola, D A; Permalloo, N; Cordery, R J; Anderson, S R
Pregnant women in England are now offered seasonal influenza vaccine. Midwives could be influential in promoting this, but specific information on their views on the policy and their role in its implementation is lacking. London midwives were surveyed for their views on the new policy and their own vaccine uptake, using an anonymously self-completed semi-structured online survey via a convenience sampling approach. In total, 266 midwives responded. Sixty-nine percent agreed with the policy of vaccinating all pregnant women. Seventy-six percent agreed that midwives should routinely advise pregnant women on vaccination, but only 25% felt adequately prepared for this role. Just 28% wished to be vaccinators, due to concerns about increased workload and inadequate training. Forty-three percent received seasonal influenza vaccine themselves. Major reasons for non-uptake were doubts about vaccine necessity (34%), safety (25%) and effectiveness (10%); and poor arrangements for vaccination (11%). Suggested strategies for improving their own uptake included better access to evidence of effectiveness (67%) and improved work-based vaccination (45%). London midwives support influenza vaccination of pregnant women, but are more willing to give advice on, than to administer, the vaccine. Midwives' own influenza vaccine uptake could improve with more information and easier access to vaccination in their workplace.
Full Text Available While influenza virus diversity and antigenic drift have been well characterized on a global scale, the factors that influence the virus' rapid evolution within and between human hosts are less clear. Given the modest effectiveness of seasonal vaccination, vaccine-induced antibody responses could serve as a potent selective pressure for novel influenza variants at the individual or community level. We used next generation sequencing of patient-derived viruses from a randomized, placebo-controlled trial of vaccine efficacy to characterize the diversity of influenza A virus and to define the impact of vaccine-induced immunity on within-host populations. Importantly, this study design allowed us to isolate the impact of vaccination while still studying natural infection. We used pre-season hemagglutination inhibition and neuraminidase inhibition titers to quantify vaccine-induced immunity directly and to assess its impact on intrahost populations. We identified 166 cases of H3N2 influenza over 3 seasons and 5119 person-years. We obtained whole genome sequence data for 119 samples and used a stringent and empirically validated analysis pipeline to identify intrahost single nucleotide variants at ≥1% frequency. Phylogenetic analysis of consensus hemagglutinin and neuraminidase sequences showed no stratification by pre-season HAI and NAI titer, respectively. In our study population, we found that the vast majority of intrahost single nucleotide variants were rare and that very few were found in more than one individual. Most samples had fewer than 15 single nucleotide variants across the entire genome, and the level of diversity did not significantly vary with day of sampling, vaccination status, or pre-season antibody titer. Contrary to what has been suggested in experimental systems, our data indicate that seasonal influenza vaccination has little impact on intrahost diversity in natural infection and that vaccine-induced immunity may be only a
Full Text Available Current egg-based influenza vaccine production technology can't promptly meet the global demand during an influenza pandemic as shown in the 2009 H1N1 pandemic. Moreover, its manufacturing capacity would be vulnerable during pandemics caused by highly pathogenic avian influenza viruses. Therefore, vaccine production using mammalian cell technology is becoming attractive. Current influenza H5N1 vaccine strain (NIBRG-14, a reassortant virus between A/Vietnam/1194/2004 (H5N1 virus and egg-adapted high-growth A/PR/8/1934 virus, could grow efficiently in eggs and MDCK cells but not Vero cells which is the most popular cell line for manufacturing human vaccines. After serial passages and plaque purifications of the NIBRG-14 vaccine virus in Vero cells, one high-growth virus strain (Vero-15 was generated and can grow over 10(8 TCID(50/ml. In conclusion, one high-growth H5N1 vaccine virus was generated in Vero cells, which can be used to manufacture influenza H5N1 vaccines and prepare reassortant vaccine viruses for other influenza A subtypes.
Nunes, Marta C; Madhi, Shabir A
Pregnant women are considered to be susceptible to severe influenza illness and are recommended as a priority group to be targeted for influenza vaccination in countries with vaccination programs. Increased rates of poor birth outcomes have also been temporally associated with influenza infection, especially when pandemics strains emerge. Even though the primary purpose for influenza vaccination during pregnancy is to decrease the risk of influenza infection in the women, other potential bene...
Alfelali, Mohammad; Barasheed, Osamah; Badahdah, Al-Mamoon; Bokhary, Hamid; Azeem, Mohammed I; Habeebullah, Turki; Bakarman, Marwan; Asghar, Atif; Booy, Robert; Rashid, Harunor
Hajj is the world's largest annual mass gathering that attracts two to three million Muslims from around the globe to a religious assemblage in Makkah, Saudi Arabia. The risk of acquisition and transmission of influenza among Hajj pilgrims is high. Therefore, influenza vaccination is recommended, and was monitored frequently among pilgrims from different countries. However, the vaccination uptake among Saudi pilgrims has not been assessed in recent years. This analysis aims to evaluate influenza vaccine uptake among Saudi Hajj pilgrims, and identify the key barriers to vaccination. Data on influenza vaccination were obtained from Saudi pilgrims who took part in a large trial during the Hajj of 2013, 2014 and 2015. Pilgrims were met and recruited in Mina, Makkah during the peak period of Hajj and were asked to complete a baseline questionnaire that recorded their influenza vaccination history, including reason(s) for non-receipt of vaccine. A total of 6974 Saudi pilgrims aged between 18 and 95 (median 34) years were recruited; male to female ratio was 1:1.2. Of the total, 90.8% declared their influenza vaccination history, 51.3% of them reported receiving influenza vaccine before travel to Hajj. The vaccination rates for the years 2013, 2014 and 2015 were 21.4%, 48.2% and 58.1%, respectively (P Saudi Hajj pilgrims is increasing over years but still needs further improvement. Lack of awareness and misperceptions are the main barriers. Education of Saudi pilgrims and health professionals is required to raise awareness about influenza vaccination. Further studies are needed to understand pilgrims' misperceptions. Copyright © 2018 Elsevier Ltd. All rights reserved.
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.
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
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…
Saluja, Vinay; Amorij, Jean P; van Roosmalen, Maarten L; Leenhouts, Kees; Huckriede, Anke; Hinrichs, Wouter L J; Frijlink, Henderik W
Nasal administration of influenza vaccine has the potential to facilitate influenza control and prevention. However, when administered intranasally (i.n.), commercially available inactivated vaccines only generate systemic and mucosal immune responses if strong adjuvants are used, which are often
Silva, M.L.; Perrier, L.; Cohen, J.M.; Paget, W.J.; Mosnier, A.; Späth, H.M.
Objectives: To conduct a literature review of influenza vaccination policy, describing roles and interactions between stakeholders and the factors influencing policy-making. Methods: Major databases were searched using keywords related to influenza vaccination, decision-making and healthpolicy.
... 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: ...
Cyril Jean-Marie Martel
Full Text Available Trivalent inactivated vaccines (TIV against influenza are given to 350 million people every year. Most of these are non-adjuvanted vaccines whose immunogenicity and protective efficacy are considered suboptimal. Commercially available non-adjuvanted TIV are known to elicit mainly a humoral immune response, whereas the induction of cell-mediated immune responses is negligible. Recently, a cationic liposomal adjuvant (dimethyldioctadecylammonium/trehalose 6,6'-dibehenate, CAF01 was developed. CAF01 has proven to enhance both humoral and cell-mediated immune responses to a number of different experimental vaccine candidates. In this study, we compared the immune responses in ferrets to a commercially available TIV with the responses to the same vaccine mixed with the CAF01 adjuvant. Two recently circulating H1N1 viruses were used as challenge to test the vaccine efficacy. CAF01 improved the immunogenicity of the vaccine, with increased influenza-specific IgA and IgG levels. Additionally, CAF01 promoted cellular-mediated immunity as indicated by interferon-gamma expressing lymphocytes, measured by flow cytometry. CAF01 also enhanced the protection conferred by the vaccine by reducing the viral load measured in nasal washes by RT-PCR. Finally, CAF01 allowed for dose-reduction and led to higher levels of protection compared to TIV adjuvanted with a squalene emulsion. The data obtained in this human-relevant challenge model supports the potential of CAF01 in future influenza vaccines.
Influenza is an acute viral respiratory illness that continues to cause significant morbidity and mortality in Ireland. Despite well-established national and international guidelines1 and increased public awareness campaigns, vaccine uptake rates are well below target worldwide2. We performed an audit of influenza vaccine uptake at a Respiratory outpatient clinic in a tertiary referral centre. 54% (n=41) of patients received the annual vaccine, well below the target of 75% set by the European Centre for Disease Prevention and Control (ECDC).
Peleg, Noam; Zevit, Noam; Shamir, Raanan; Chodick, Gabriel; Levy, Itzhak
Despite advances in the treatment and prevention of influenza, it is still considered an important cause of morbidity and mortality worldwide. Annual vaccination is the safest and most effective mean of prevention. Our study aims were to explore the uptake of influenza vaccination among children with gastrointestinal disorders, and to characterize non-adherent patients. The present cross-sectional study included parents of pediatric patients attending the Gastroenterology Institute at Schneider Children's Medical Center of Israel between September and October 2011. Parents were asked to complete a questionnaire concerning demographic and clinical parameters, influenza vaccination of the child, and reasons for not vaccinating the child, when appropriate. The study population included 273 patients (50% female), with a median age of 10 years (range, 2-18 years). Overall, the rate of seasonal influenza vaccination was 30.8%. Higher rates were found among immunosuppressed patients (46.1%), and in patients with inflammatory bowel disease (50%). There was no significant effect of patient age, gender, ethnic origin or parental level of education on the vaccination rate. Vaccination rates were significantly associated with parents' information and knowledge of, as well as their personal beliefs regarding the vaccine (Pvaccination rates are relatively low in the pediatric population attending gastroenterology clinics, in both high- and low-risk groups. The importance of parental knowledge in compliance with influenza vaccination of children should prompt general pediatricians and gastroenterologists to discuss and address the common misconceptions regarding the vaccine. Copyright © 2014 Elsevier Ltd. All rights reserved.
Full Text Available Introduction: Recent report on existence of a stem region of hemagglutinin has arisen new hopes for vaccination of influenza A as it consist of a conserve fusion peptide shared across several influenza subtypes and can be targeted by human immune system. Methods: Given that traditional vaccination based on live attenuated viruses often fails to surpass such viral infection, a great deal of attention has been devoted to develop a safe yet efficient system for vaccination influenza A. We believe that a natural bioshuttle can be recruited for spontaneous mass vaccination. Results: Thus, here, we hypothesize that a bioengineered transgenic Hirudo medicinalis can be considered as an alive bioshuttle for in-situ vaccination against influenza A virus. By introducing the designated gene(s encoding the target fragment (i.e., stem region of hemagglutinin, this microsurgeon can act as a rapid microproducer of viral proteins for in-house mass vaccination through imparting the necessary proteins such as those, naturally presented in leech's saliva. Conclusion: This peculiar bioshuttle can be easily exploited as a medical modality choice at home resulting in greater patient compliance.
Ott, Jördis J.; Klein Breteler, Janna; Tam, John S.; Hutubessy, Raymond C.W.; Jit, Mark; de Boer, Michiel R.
Objectives: Economic evaluations on influenza vaccination from low resource settings are scarce and have not been evaluated using a systematic approach. Our objective was to conduct a systematic review on the value for money of influenza vaccination in low- and middle-income countries. Methods: PubMed and EMBASE were searched for economic evaluations published in any language between 1960 and 2011. Main outcome measures were costs per influenza outcome averted, costs per quality-adjusted life years gained or disability-adjusted life years averted, costs per benefit in monetary units or cost-benefit ratios. Results: Nine economic evaluations on seasonal influenza vaccine met the inclusion criteria. These were model- or randomized-controlled-trial (RCT)-based economic evaluations from middle-income countries. Influenza vaccination provided value for money for elderly, infants, adults and children with high-risk conditions. Vaccination was cost-effective and cost-saving for chronic obstructive pulmonary disease patients and in elderly above 65 y from model-based evaluations, but conclusions from RCTs on elderly varied. Conclusion: Economic evaluations from middle income regions differed in population studied, outcomes and definitions used. Most findings are in line with evidence from high-income countries highlighting that influenza vaccine is likely to provide value for money. However, serious methodological limitations do not allow drawing conclusions on cost-effectiveness of influenza vaccination in middle income countries. Evidence on cost-effectiveness from low-income countries is lacking altogether, and more information is needed from full economic evaluations that are conducted in a standardized manner. PMID:23732900
Karlsson, Ingrid; Borggren, Marie; Rosenstierne, Maiken Worsøe
Background Influenza A virus in swine herds represents a major problem for the swine industry and poses a constant threat for the emergence of novel pandemic viruses and the development of more effective influenza vaccines for pigs is desired. By optimizing the vector backbone and using a needle...... needle-free delivery to the skin, we immunized pigs with two different doses (500 μg and 800 μg) of an influenza DNA vaccine based on six genes of pandemic origin, including internally expressed matrix and nucleoprotein and externally expressed hemagglutinin and neuraminidase as previously demonstrated....... Two weeks following immunization, the pigs were challenged with the 2009 pandemic H1N1 virus. Results When challenged with 2009 pandemic H1N1, 0/5 vaccinated pigs (800 μg DNA) became infected whereas 5/5 unvaccinated control pigs were infected. The pigs vaccinated with the low dose (500 μg DNA) were...
M. P. Kostinov
Full Text Available Recent epidemiological events showed that pregnant women are the most vulnerable part of population if there is the flu in the country and they die much more often than the rest part of people. That is why influenza vaccination of population including pregnant women is one of the priorities of public health service in our state. Worldwide experience of influenza vaccination of either adults or children by new adjuvant vaccine has caused our research of its efficiency among pregnant women. The aim of the study was to investigate the level of antibodies to influenza virus strain A/H1N1/v, A/H3N2 and B in pregnant women vaccinated adjuvant trivalent subunit vaccine. Our research is randomized and comparative on parallel groups. It was carried out within the demands of Russian Federation and International ethic norms adapted to such kind of researches. Evaluation of the immunogenicity of the vaccine was conducted in 27 pregnant women in the II trimester of gestation, and in 23 pregnant women in the III trimester of gestation, 19 non-pregnant women was in the control group. The level of antibodies in the serum was determined using a reaction of hemagglutination inhibition before and 1, 3, 6, 9 and 12 months after the vaccination. Revealed that influenza vaccination of pregnant women in the II and III trimester, causes the increase in titers of antibodies to vaccine influenza strains A and B, to fully meet the required criteria CPMP, and does not differ from the nonpregnant group. In a month after vaccination the level of seroprotective against A/H1N1/v was 77.0%, A/H3N2 — 88.9%, B — 85.2% after vaccination in II trimester, and 87.0; 87.0; 91.35% in III trimester of gestation. The factor of seroconversion after vaccination in II trimester for A/H1N1/v was equal to 6.5, A/H3N2 — 7.2, B — 6.5, after vaccination in III trimester of pregnancy: 7.1, 6.5 and 5.1 correspondingly. At the same time revealed accelerated decline in antibody titer against
Nakatsukasa, Akihiro; Kuruma, Koji; Okamatsu, Masatoshi; Hiono, Takahiro; Suzuki, Mizuho; Matsuno, Keita; Kida, Hiroshi; Oyamada, Takayoshi; Sakoda, Yoshihiro
Transdermal vaccination using a microneedle (MN) confers enhanced immunity compared with subcutaneous (SC) vaccination. Here we developed a novel dissolving MN patch for the influenza vaccine. The potencies of split virion and whole virus particle (WVP) vaccines prepared from A/Puerto Rico/8/1934 (H1N1) and A/duck/Hokkaido/Vac-3/2007 (H5N1), respectively, were evaluated. MN vaccination induced higher neutralizing antibody responses than SC vaccination in mice. Moreover, MN vaccination with a lower dose of antigens conferred protective immunity against lethal challenges of influenza viruses than SC vaccination in mice. These results suggest that the WVP vaccines administered using MN are an effective combination for influenza vaccine to be further validated in humans. Copyright © 2017 Elsevier Ltd. All rights reserved.
Crepey, Pascal; de Boer, Pieter T.; Postma, Maarten J.; Pitman, Richard
IntroductionVaccination is an effective preventive strategy against influenza. However, current trivalent influenza vaccines (TIVs) contain only one of the two influenza B lineages that circulate each year. Vaccine mismatches are frequent because predicting which one will predominate is difficult.
Crépey, P.; De Boer, P.; Postma, M.J.; Pitman, R.J.
Objectives: Vaccination has proven to be an efficient preventive strategy against influenza infection. Each year, two genetically distinct influenza B lineages cocirculate. Current trivalent influenza vaccines (TIVs) contain only one influenza B and two influenza A strains, but vaccine mismatch are
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.
Dorribo, V; Lazor-Blanchet, C; Hugli, O; Zanetti, G
Vaccination of health care workers (HCW) against seasonal influenza (SI) is recommended but vaccination rate rarely reach >30%. Vaccination coverage against 2009 pandemic influenza (PI) was 52% in our hospital, whilst a new policy requiring unvaccinated HCW to wear a mask during patient care duties was enforced. To investigate the determinants of this higher vaccination acceptance for PI and to look for an association with the new mask-wearing policy. A retrospective cohort study, involving HCW of three critical departments of a 1023-bed, tertiary-care university hospital in Switzerland. Self-reported 2009-10 SI and 2009 PI vaccination statuses, reasons and demographic data were collected through a literature-based questionnaire. Descriptive statistics, uni- and multivariate analyses were then performed. There were 472 respondents with a response rate of 54%. Self-reported vaccination acceptance was 64% for PI and 53% for SI. PI vaccination acceptance was associated with being vaccinated against SI (OR 9.5; 95% CI 5.5-16.4), being a physician (OR 7.7; 95% CI 3.1-19.1) and feeling uncomfortable wearing a mask (OR 1.7; 95% CI 1.0-2.8). Main motives for refusing vaccination were: preference for wearing a surgical mask (80% for PI, not applicable for SI) and concerns about vaccine safety (64%, 50%) and efficacy (44%, 35%). The new mask-wearing policy was a motivation for vaccination but also offered an alternative to non-compliant HCW. Concerns about vaccine safety and efficiency and self-interest of health care workers are still main determinants for influenza vaccination acceptance. Better incentives are needed to encourage vaccination amongst non-physician HCW. © The Author 2015. Published by Oxford University Press on behalf of the Society of Occupational Medicine. All rights reserved. For Permissions, please email: firstname.lastname@example.org.
Pedroza, Alvaro; Huerta, José G; Garcia, Maria de la Luz; Rojas, Arsheli; López-Martínez, Irma; Penagos, Martín; Franco-Paredes, Carlos; Deroche, Christele; Mascareñas, Cesar
The morbidity and mortality associated with influenza is substantial in children with asthma. There are no available data on the safety and immunogenicity of influenza vaccine in children with asthma in Latin America. Furthermore, it is unclear if influenza vaccination may cause asthma exacerbations. We conducted a placebo-controlled trial to investigate the safety and immunogenicity of an inactivated trivalent split virus influenza vaccine in children with asthma in Mexico. We also measured the impact of influenza vaccination on pulmonary function tests in this population. The inactivated influenza vaccine was immunogenic and safe in terms of local and systemic side effects compared to placebo. We observed no significant impact on pulmonary function tests among vaccine recipients. Given the significant morbidity associated with influenza in children, strategies to promote increased influenza vaccination coverage in this high-risk group in Latin America and elsewhere are urgently needed.
Full Text Available Simple and effective vaccine administration is particularly important for annually recommended influenza vaccination. We hypothesized that vaccine delivery to the skin using a patch containing vaccine-coated microneedles could be an attractive approach to improve influenza vaccination compliance and efficacy.Solid microneedle arrays coated with inactivated influenza vaccine were prepared for simple vaccine delivery to the skin. However, the stability of the influenza vaccine, as measured by hemagglutination activity, was found to be significantly damaged during microneedle coating. The addition of trehalose to the microneedle coating formulation retained hemagglutination activity, indicating stabilization of the coated influenza vaccine. For both intramuscular and microneedle skin immunization, delivery of un-stabilized vaccine yielded weaker protective immune responses including viral neutralizing antibodies, protective efficacies, and recall immune responses to influenza virus. Immunization using un-stabilized vaccine also shifted the pattern of antibody isotypes compared to the stabilized vaccine. Importantly, a single microneedle-based vaccination using stabilized influenza vaccine was found to be superior to intramuscular immunization in controlling virus replication as well as in inducing rapid recall immune responses post challenge.The functional integrity of hemagglutinin is associated with inducing improved protective immunity against influenza. Simple microneedle influenza vaccination in the skin produced superior protection compared to conventional intramuscular immunization. This approach is likely to be applicable to other vaccines too.
S. A. Donina
Full Text Available Abstract. At present, immunogenicity evaluation of influenza vaccines is performed by quantitative assessment of increased serum antibodies. It was, however, shown that the degree of human defense against influenza is mostly related to their qualitative characteristics, i.e., avidity (functional activity. Leading role of local immunity is demonstrated in protection against influenza. Such immunity is mediated by IgA antibodies from mucosal airways. Meanwhile, the avidity issues for local antibodies still remain open.In present study, an attempt was undertaken to evaluate post-vaccination local immunological memory for influenza A virus, according to IgA antibodies from upper respiratory secretions. Two techniques were used to evaluate antibody avidity, that were previously applied for studying this phenomenon with serum imunoglobulins, i.e., a dynamic test (measurement of antigen-antibody reaction rates, and a test with urea, a chaotropic agent (avidity is determined as a strength of antigen-antibody complex. A total of 202 persons (18 to 20 years old were enrolled into the study.With both tests, a broad range of individual avidity values was observed for the antibodies. A significant cohort (up to 30 per cent of persons immunized with live influenza vaccine, showed sharply increased avidity of secretory IgA antibodies by both methods, along with accumulation of these immunoglobulins after vaccination. A reverse relationship is revealed between avidity levels of these antibodies before vaccination, and increase of this parameter post-immunization. The data present convincing arguments for specific renewal of local humoral immunological memory, as induced by live influenza vaccine. The study substantiates a necessity for application of the both tests in parallel, when determining avidity of secretory IgA antibodies. (Med. Immunol., vol. 10, N 4-5, pp 423-430.
Grant, Emma J; Quiñones-Parra, Sergio M; Clemens, E Bridie; Kedzierska, Katherine
Influenza A viruses (IAVs) cause significant morbidity and mortality worldwide, despite new strain-specific vaccines being available annually. As IAV-specific CD8(+) T cells promote viral control in the absence of neutralizing antibodies, and can mediate cross-reactive immunity toward distinct IAVs to drive rapid recovery from both mild and severe influenza disease, there is great interest in developing a universal T cell vaccine. However, despite detailed studies in mouse models of influenza virus infection, there is still a paucity of data on human epitope-specific CD8(+) T cell responses to IAVs. This review focuses on our current understanding of human CD8(+) T cell immunity against distinct IAVs and discusses the possibility of achieving a CD8(+) T cell mediated-vaccine that protects against multiple, distinct IAV strains across diverse human populations. We also review the importance of CD8(+) T cell immunity in individuals highly susceptible to severe influenza infection, including those hospitalised with influenza, the elderly and Indigenous populations. Copyright © 2016 Elsevier B.V. All rights reserved.
A.C.G. Voordouw (Bettie)
textabstractAn influenza epidemic was first described in 1173, although there are reports of influenza as early as 412 BC. Recurrent epidemics and incidental pandemics caused by influenza virus are documented since the last 400 years. These were based upon clinical observation and epidemiology.
Kamis, Arnold; Zhang, Yuji; Kamis, Tamara
Vaccinating adults against influenza remains a challenge in the United States. Using data from the Centers for Disease Control and Prevention, we present a model for predicting who receives influenza vaccination in the United States between 2012 and 2014, inclusive. The logistic regression model contains nine predictors: age, pneumococcal vaccination, time since last checkup, highest education level attained, employment, health care coverage, number of personal doctors, smoker status, and annual household income. The model, which classifies correctly 67 percent of the data in 2013, is consistent with models tested on the 2012 and 2014 datasets. Thus, we have a multiyear model to explain and predict influenza vaccination in the United States. The results indicate room for improvement in vaccination rates. We discuss how cognitive biases may underlie reluctance to obtain vaccination. We argue that targeted communications addressing cognitive biases could be useful for effective framing of vaccination messages, thus increasing the vaccination rate. Finally, we discuss limitations of the current study and questions for future research.
Vernon J Lee
Full Text Available 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.
Hawken, Steven; Kwong, Jeffrey C; Deeks, Shelley L; Crowcroft, Natasha S; McGeer, Allison J; Ducharme, Robin; Campitelli, Michael A; Coyle, Doug; Wilson, Kumanan
It is unclear whether seasonal influenza vaccination results in a net increase or decrease in the risk for Guillain-Barré syndrome (GBS). To assess the effect of seasonal influenza vaccination on the absolute risk of acquiring GBS, we used simulation models and published estimates of age- and sex-specific risks for GBS, influenza incidence, and vaccine effectiveness. For a hypothetical 45-year-old woman and 75-year-old man, excess GBS risk for influenza vaccination versus no vaccination was -0.36/1 million vaccinations (95% credible interval -1.22% to 0.28) and -0.42/1 million vaccinations (95% credible interval, -3.68 to 2.44), respectively. These numbers represent a small absolute reduction in GBS risk with vaccination. Under typical conditions (e.g. influenza incidence rates >5% and vaccine effectiveness >60%), vaccination reduced GBS risk. These findings should strengthen confidence in the safety of influenza vaccine and allow health professionals to better put GBS risk in context when discussing influenza vaccination with patients.
Robert B Couch
Full Text Available BACKGROUND: Concern for a pandemic caused by a newly emerged avian influenza A virus has led to clinical trials with candidate vaccines as preparation for such an event. Most trials have involved vaccines for influenza A (H5N1, A (H7N7 or A (H9N2. OBJECTIVE: To evaluate dosage-related safety and immunogenicity of an inactivated influenza A (H7N7 vaccine in humans. DESIGN: One hundred twenty-five healthy young adults were randomized to receive two doses intramuscularly of placebo or 7.5, 15, 45 or 90 µg of HA of an inactivated subunit influenza A (H7N7 vaccine (25 per group, four weeks apart. Reactogenicity was evaluated closely for one week and for any adverse effect for six months after each dose. Serum hemagglutination-inhibiting and neutralizing antibody responses were determined four weeks after each dose and at six months. RESULTS: Reactogenicity evaluations indicated the vaccinations were well tolerated. Only one subject developed a ≥4-fold serum hemagglutination-inhibition (HAI antibody response and a final titer of ≥1:40 four weeks after dose two and only five subjects developed a neutralizing antibody rise and a final titer of ≥1:40 in tests performed at a central laboratory. Four of the five were given the 45 or 90 µg HA dosage. A more sensitive HAI assay at the study site revealed a dose-response with increasing HA dosage but only 36% in the 90 µg HA group developed a ≥4-fold rise in antibody in this test and only one of these achieved a titer of ≥1:32. CONCLUSION: This inactivated subunit influenza A (H7N7 vaccine was safe but poorly immunogenic in humans. TRIALS REGISTRATION: ClinicalTrials.gov NCT00546585.
Zerbini, Cristiano A.F.; Ribeiro dos Santos, Rodrigo; Jose Nunes, Maria; Soni, Jyoti; Li, Ping; Jain, Varsha K.; Ofori-Anyinam, Opokua
Abstract The World Health Organization influenza forecast now includes an influenza B strain from each of the influenza B lineages (B/Yamagata and B/Victoria) for inclusion in seasonal influenza vaccines. Traditional trivalent influenza vaccines include an influenza B strain from one lineage, but because two influenza B lineages frequently co-circulate, the effectiveness of trivalent vaccines may be reduced in seasons of influenza B vaccine-mismatch. Thus, quadrivalent vaccines may potentiall...
Inspecting the Mechanism: A Longitudinal Analysis of Socioeconomic Status Differences in Perceived Influenza Risks, Vaccination Intentions, and Vaccination Behaviors during the 2009-2010 Influenza Pandemic.
Influenza vaccination is strongly associated with socioeconomic status, but there is only limited evidence on the respective roles of socioeconomic differences in vaccination intentions versus corresponding differences in follow-through on initial vaccination plans for subsequent socioeconomic differences in vaccine uptake. Nonparametric mean smoothing, linear regression, and probit models were used to analyze longitudinal survey data on perceived influenza risks, behavioral vaccination intentions, and vaccination behavior of adults during the 2009-2010 influenza A/H1N1 ("swine flu") pandemic in the United States. Perceived influenza risks and behavioral vaccination intentions were elicited prior to the availability of H1N1 vaccine using a probability scale question format. H1N1 vaccine uptake was assessed at the end of the pandemic. Education, income, and health insurance coverage displayed positive associations with behavioral intentions to get vaccinated for pandemic influenza while employment was negatively associated with stated H1N1 vaccination intentions. Education and health insurance coverage also displayed significant positive associations with pandemic vaccine uptake. Moreover, behavioral vaccination intentions showed a strong and statistically significant positive partial association with later H1N1 vaccination. Incorporating vaccination intentions in a statistical model for H1N1 vaccine uptake further highlighted higher levels of follow-through on initial vaccination plans among persons with higher education levels and health insurance. Sampling bias, misreporting in self-reported data, and limited generalizability to nonpandemic influenza are potential limitations of the analysis. Closing the socioeconomic gap in influenza vaccination requires multipronged strategies that not only increase vaccination intentions by improving knowledge, attitudes, and beliefs but also facilitate follow-through on initial vaccination plans by improving behavioral
A cross-sectional survey was undertaken with the European Union (EU) Member States and Norway and Iceland to describe seasonal influenza immunisation in the 2006-7 season, in particular to identify country-specific recommendations for risk groups, obtain vaccine uptake information and allow comparison with global recommendations. A standardised questionnaire was completed electronically by each country\\'s project gatekeeper. Of the 29 countries surveyed, 28 recommended seasonal influenza vaccination for older age groups (22 for those aged > 65 years), and in one country vaccine was recommended for all age groups. All countries recommended vaccinating patients with chronic pulmonary and cardiovascular diseases and most countries advised to immunise patients with haematologic or metabolic disorders (n=28), immunologic disorders (n=27) and renal disease (n=27), as well as residents of long-term care facilities (n=24). Most countries recommended vaccination for staff in hospitals (n=25), long-term care facilities (n=25) and outpatient clinics (n=23), and one-third had such recommendations for workers in essential (n=10), military (n=10) and veterinary services (n=10) and poultry industry (n=13). Eight countries recommended vaccine for pregnant women; and five advised to vaccinate children (with age limits ranging from 6 months to 5 years). Twenty countries measured influenza vaccine uptake among those aged > 65 years (range 1.8%-82.1%), seven reported uptake in healthcare workers (range 14%-48%) and seven assessed coverage in persons with underlying medical conditions (range 27.6%-75.2%). The data provided by this study can assist EU states to assess and compare their influenza vaccination programme performance with other countries. The information provides a comprehensive overview of policies and programmes and their outcomes and can be used to inform joint discussions on how the national policies in the EU might be standardised in the future to achieve optimal
Mereckiene, J; Cotter, S; Nicoll, A; Levy-Bruhl, D; Ferro, A; Tridente, G; Zanoni, G; Berra, P; Salmaso, S; O'Flanagan, D; O Flanagan, D
A cross-sectional survey was undertaken with the European Union (EU) Member States and Norway and Iceland to describe seasonal influenza immunisation in the 2006-7 season, in particular to identify country-specific recommendations for risk groups, obtain vaccine uptake information and allow comparison with global recommendations. A standardised questionnaire was completed electronically by each country's project gatekeeper. Of the 29 countries surveyed, 28 recommended seasonal influenza vaccination for older age groups (22 for those aged > 65 years), and in one country vaccine was recommended for all age groups. All countries recommended vaccinating patients with chronic pulmonary and cardiovascular diseases and most countries advised to immunise patients with haematologic or metabolic disorders (n=28), immunologic disorders (n=27) and renal disease (n=27), as well as residents of long-term care facilities (n=24). Most countries recommended vaccination for staff in hospitals (n=25), long-term care facilities (n=25) and outpatient clinics (n=23), and one-third had such recommendations for workers in essential (n=10), military (n=10) and veterinary services (n=10) and poultry industry (n=13). Eight countries recommended vaccine for pregnant women; and five advised to vaccinate children (with age limits ranging from 6 months to 5 years). Twenty countries measured influenza vaccine uptake among those aged > 65 years (range 1.8%-82.1%), seven reported uptake in healthcare workers (range 14%-48%) and seven assessed coverage in persons with underlying medical conditions (range 27.6%-75.2%). The data provided by this study can assist EU states to assess and compare their influenza vaccination programme performance with other countries. The information provides a comprehensive overview of policies and programmes and their outcomes and can be used to inform joint discussions on how the national policies in the EU might be standardised in the future to achieve optimal
Full Text Available Although current influenza vaccines are effective in general, there is an urgent need for the development of new technologies to improve vaccine production timelines, capacities and immunogenicity. Herein, we describe the development of an influenza vaccine technology which enables recombinant production of highly efficient influenza vaccines in bacterial expression systems. The globular head domain of influenza hemagglutinin, comprising most of the protein's neutralizing epitopes, was expressed in E. coli and covalently conjugated to bacteriophage-derived virus-like particles produced independently in E.coli. Conjugate influenza vaccines produced this way were used to immunize mice and found to elicit immune sera with high antibody titers specific for the native influenza hemagglutinin protein and high hemagglutination-inhibition titers. Moreover vaccination with these vaccines induced full protection against lethal challenges with homologous and highly drifted influenza strains.
Comparison of egg and high yielding MDCK cell-derived live attenuated influenza virus for commercial production of trivalent influenza vaccine: in vitro cell susceptibility and influenza virus replication kinetics in permissive and semi-permissive cells.
Hussain, Althaf I; Cordeiro, Melissa; Sevilla, Elizabeth; Liu, Jonathan
Currently MedImmune manufactures cold-adapted (ca) live, attenuated influenza vaccine (LAIV) from specific-pathogen free (SPF) chicken eggs. Difficulties in production scale-up and potential exposure of chicken flocks to avian influenza viruses especially in the event of a pandemic influenza outbreak have prompted evaluation and development of alternative non-egg based influenza vaccine manufacturing technologies. As part of MedImmune's effort to develop the live attenuated influenza vaccine (LAIV) using cell culture production technologies we have investigated the use of high yielding, cloned MDCK cells as a substrate for vaccine production by assessing host range and virus replication of influenza virus produced from both SPF egg and MDCK cell production technologies. In addition to cloned MDCK cells the indicator cell lines used to evaluate the impact of producing LAIV in cells on host range and replication included two human cell lines: human lung carcinoma (A549) cells and human muco-epidermoid bronchiolar carcinoma (NCI H292) cells. The influenza viruses used to infect the indicators cell lines represented both the egg and cell culture manufacturing processes and included virus strains that composed the 2006-2007 influenza seasonal trivalent vaccine (A/New Caledonia/20/99 (H1N1), A/Wisconsin/67/05 (H3N2) and B/Malaysia/2506/04). Results from this study demonstrate remarkable similarity between influenza viruses representing the current commercial egg produced and developmental MDCK cell produced vaccine production platforms. MedImmune's high yielding cloned MDCK cells used for the cell culture based vaccine production were highly permissive to both egg and cell produced ca attenuated influenza viruses. Both the A549 and NCI H292 cells regardless of production system were less permissive to influenza A and B viruses than the MDCK cells. Irrespective of the indicator cell line used the replication properties were similar between egg and the cell produced
Basra, Gurjot; Jajoria, Praveen; Gonzalez, Emilio
Rheumatoid arthritis (RA) is the most common chronic inflammatory joint disease. Multiple scientific articles have documented that vaccinations for influenza, MMR, and HBV, to name a few, could be triggers of RA in genetically predisposed individuals. However, there is limited data regarding the association of swine flu vaccine (H1N1) and RA. We report the case of a Mexican American female who developed RA right after vaccination with H1N1 vaccine. Genetically, RA has consistently been associated with an epitope in the third hypervariable region of the HLA-DR β chains, known as the "shared epitope", which is found primarily in DR4 and DR1 regions. The presence of HLA-DRB1 alleles is associated with susceptibility to RA in Mexican Americans. Hence, certain individuals with the presence of the "shared epitope" may develop RA following specific vaccinations. To our knowledge, this is the first reported case of RA following vaccination with the swine flu vaccine.
Bednarczyk, Robert A; Chu, Samantha L; Sickler, Heather; Shaw, Jana; Nadeau, Jessica A; McNutt, Louise-Anne
Annual influenza vaccine coverage for young adults (including college students) remains low, despite a 2011 US recommendation for annual immunization of all people 6 months and older. College students are at high risk for influenza morbidity given close living and social spaces and extended travel during semester breaks when influenza circulation typically increases. We evaluated influenza vaccine uptake following an on-campus vaccine campaign at a large, public New York State university. Consecutive students visiting the University Health Center were recruited for a self-administered, anonymous, written survey. Students were asked about recent influenza vaccination, barriers to influenza vaccination, and willingness to get vaccinated to protect other vulnerable individuals they may encounter. Frequencies and proportions were evaluated. Of 653 students approached, 600 completed surveys (92% response proportion); respondents were primarily female (61%) and non-Hispanic white (59%). Influenza vaccine coverage was low (28%). Compared to coverage among non-Hispanic white students (30%), coverage was similar among Hispanic (30%) and other race/ethnicity students (28%) and lowest among non-Hispanic black students (17%). Among the unvaccinated, the most commonly selected vaccination barriers were "Too lazy to get the vaccine" (32%) and "Don't need the vaccine because I'm healthy" (29%); 6% of unvaccinated students cited cost as a barrier. After being informed that influenza vaccination of young, healthy people can protect other vulnerable individuals (e.g., infants, elderly), 71% of unvaccinated students indicated this would increase their willingness to get vaccinated. Influenza vaccine uptake among college students is very low. While making vaccine easily obtained may increase vaccine uptake, college students need to be motivated to get vaccinated. Typically healthy students may not perceive a need for influenza vaccine. Education about vaccinating healthy individuals
... factors for developing them, such as taking oral contraceptives . A safety review of Gardasil in Denmark and ... and venous thromboembolic adverse events after immunisation of adolescent girls with quadrivalent human papillomavirus vaccine in Denmark ...
Ülkü Aka Aktürk
Full Text Available Background: Influenza and pneumococcal vaccinations are recommended in chronic obstructive pulmonary disease patients to decrease associated risks at all stages. Although the prevalence of chronic obstructive pulmonary disease is high in our country, as previously reported, vaccination rates are low. Aims: To assess the vaccination rates of chronic obstructive pulmonary disease patients and factors that may affect these. Study Design: Multi-centre cross-sectional study. Methods: Patients admitted to the chest diseases clinics of six different centres between 1 February 2013 and 1 January 2014 with a pre-diagnosis of Chronic obstructive pulmonary disease according to the Global initiative for chronic obstructive lung disease criteria, who were in a stable condition were included in the study. The survey, which included demographic characteristics, socio-economic status, severity of disease and vaccination information, was first tested on a small patient population before the study. The survey was completed by the investigators after obtaining written informed consent. Results: The average age of the 296 included patients was 66.3±9.3 years and 91.9% were male. Of these, 36.5% had the influenza vaccination and 14.1% had the pneumococcal vaccination. The most common reason for not being vaccinated was ‘no recommendation by doctors’: 57.2% in the case of influenza vaccinations, and 46.8% in the case of pneumococcal vaccinations. Both vaccination rates were significantly higher in those patients with comorbidities (influenza vaccination p0.05. Vaccination rates were significantly higher in those with a white-collar occupation and higher education level, and who presented to a university hospital (p<0.001. Conclusion: Medical professionals do not request vaccinations as often as the International Guidelines suggest for chronic obstructive pulmonary disease patients. Awareness of the importance of these vaccinations among both doctors and patients
Steel, John; Burmakina, Svetlana V; Thomas, Colleen; Spackman, Erica; García-Sastre, Adolfo; Swayne, David E; Palese, Peter
The protection of poultry from H5N1 highly pathogenic avian influenza A (HPAI) and Newcastle disease virus (NDV) can be achieved through vaccination, as part of a broader disease control strategy. We have previously generated a recombinant influenza virus expressing, (i) an H5 hemagglutinin protein, modified by the removal of the polybasic cleavage peptide and (ii) the ectodomain of the NDV hemagglutinin-neuraminidase (HN) protein in the place of the ectodomain of influenza neuraminidase (Park MS, et al. Proc Natl Acad Sci USA 2006;103(21):8203-8). Here we show this virus is attenuated in primary normal human bronchial epithelial (NHBE) cell culture, and demonstrate protection of C57BL/6 mice from lethal challenge with an H5 HA-containing influenza virus through immunisation with the recombinant virus. In addition, in-ovo vaccination of 18-day-old embryonated chicken eggs provided 90% and 80% protection against highly stringent lethal challenge by NDV and H5N1 virus, respectively. We propose that this virus has potential as a safe in-ovo live, attenuated, bivalent avian influenza and Newcastle disease virus vaccine.
Mercer, Nicola J
Public health in Ontario delivers, promotes and provides each fall the universal influenza immunization program. This paper addresses the question of whether Ontario public health agencies are able to provide the influenza immunization program within the Ministry of Health fiscal funding envelope of $5 per dose. Actual program delivery data from the 2006 influenza season of Wellington-Dufferin-Guelph Public Health (WDGPH) were used to create a model template for influenza clinics capturing all variable costs. Promotional and administrative costs were separated from clinic costs. Maximum staff workloads were estimated. Vaccine clinics were delivered by public health staff in accordance with standard vaccine administration practices. The most significant economic variables for influenza clinics are labour costs and number of vaccines given per nurse per hour. The cost of facility rental was the only other significant cost driver. The ability of influenza clinics to break even depended on the ability to manage these cost drivers. At WDGPH, weekday flu clinics required the number of vaccines per nurse per hour to exceed 15, and for weekend flu clinics this number was greater than 21. We estimate that 20 vaccines per hour is at the limit of a safe workload over several hours. Managing cost then depends on minimizing hourly labour costs. The results of this analysis suggest that by managing the labour costs along with planning the volume of patients and avoiding expensive facilities, flu clinics can just break even. However, any increased costs, including negotiated wage increases or the move to safety needles, with a fixed revenue of $5.00 per dose will negate this conclusion.
Flood, Emuella M; Rousculp, Matthew D; Ryan, Kellie J; Beusterien, Kathleen M; Divino, Victoria M; Toback, Seth L; Sasané, Medha; Block, Stan L; Hall, Matthew C; Mahadevia, Parthiv J
Despite the recommendation from the Centers for Disease Control and Prevention that children between the ages of 6 months and 18 years be vaccinated against influenza annually, vaccination rates remain suboptimal. This study was conducted to explore factors that influence parents' decisions regarding influenza vaccination for children aged 2 to 12 years, to quantify the relative importance of these factors, to identify an appropriate theoretical model for illustrating the relationships among these factors, and to characterize parents by their likelihood of vaccinating their children against influenza. A quantitative Web-based survey was administered to a sample of parents from an online panel representative of the US population. Parents were stratified based on self-reported rates of their personal influenza vaccination (every year, sometimes, or never) and the age of their child (2-4 years or 5-12 years). The results were examined by parents' likelihood of vaccinating their child in the next year (high, medium, or low). Participants were asked to rank their agreement with statements representing various beliefs and perceptions about influenza and influenza vaccine on a scale from 1 = strongly agree to 5 = strongly disagree. Parents who indicated that they vaccinate their child every year were asked to select the drivers of their decision to vaccinate; parents who indicated that they never vaccinate their child were asked to select the barriers affecting their decision not to vaccinate; and parents who responded that they sometimes vaccinate their child were asked to select both the drivers and barriers affecting their decision. Participants were then asked to rank the importance of each driver or barrier on a scale from 1 = a little important to 5 = extremely important. Mean agreement ratings were calculated for parents' beliefs and perceptions about influenza and influenza vaccine and were compared across likelihood subgroups. Mean importance ratings of the
Opstelten, W; Hak, E; Verheij, T J; van Essen, G A
PURPOSE: Influenza vaccination has been recommended for all elderly people in The Netherlands since 1996, with greater than 80% compliance. It is unknown, however, if the addition of another vaccine to this immunization program will affect compliance. SUBJECTS AND METHODS: General practitioners
Yu, Doris S F; Low, Lisa P L; Lee, Iris F K; Lee, Diana T F; Ng, Wai Man
Older adults with major chronic illnesses are very susceptible to influenza and its serious complications, but many do not obtain vaccinations. Little is known about factors associated with intention to obtain influenza vaccination among at-risk Chinese older adults in Hong Kong. The aim of this study was to identify factors associated with intent to obtain influenza vaccination among at-risk Chinese older adults in Hong Kong. This multicenter descriptive correlational study recruited a convenience sample of 306 Chinese older adults with medical risk factors for influenza and its serious complications from the general outpatient clinics in Hong Kong. Interviews were conducted to assess intent to obtain influenza vaccination for the coming year, health beliefs about influenza, and discomfort following past vaccinations. The current influenza vaccination rate was 58.5%; only 36.3% intended to get vaccinated the following year. After controlling for clinical and demographic factors in a logistic regression model, perceived susceptibility predicted intention to obtain future vaccination (OR = 1.42, 95% CI [1.14, 1.78]), whereas postvaccination discomfort was negatively associated with intention (OR = 0.063, 95% CI [0.006, 0.63]). Intention to obtain influenza vaccination was low among at-risk Chinese older adults. Strengthening health beliefs and creating strategies to provide positive influenza vaccination experiences are possible approaches to interventions to improve uptake of influenza vaccination rates.
Okur, Gokcan [Etimesgut Military Hospital, Department of Radiology, Ankara (Turkey); Chaney, Kimberly A. [Presence St. Joseph Hospital, Department of Radiology, Elgin, IL (United States); Lomasney, Laurie M. [Loyola University Medical Center, Department of Radiology, Maywood, IL (United States)
The influenza vaccine is increasingly available to the general public and mandated by many employers in the United States. The prevalence of post-vaccination complications is likely on the rise. Complications are well known to general clinicians, but are under-reported in the imaging literature. We present four cases of post-vaccination shoulder pain with magnetic resonance imaging (MRI) findings. An intrasubstance fluid-like signal in deep muscular and/or tendinous structures was the most common finding on MRI of these four cases. Focal bone marrow signal within the humeral head and inflammatory changes in the subacromial/subdeltoid bursa were also observed. The most likely reason for a humeral intraosseous edema-like signal was presumed injection of vaccine substance directly into osseous structures that might lead to focal osteitis. In the published literature, there is little emphasis on the imaging of local injection site complications accompanying influenza vaccination. We intended to increase familiarity of MRI findings in the setting of prolonged or severe clinical symptoms following influenza vaccination through the imaging findings of these four cases. (orig.)
Okur, Gokcan; Chaney, Kimberly A.; Lomasney, Laurie M.
The influenza vaccine is increasingly available to the general public and mandated by many employers in the United States. The prevalence of post-vaccination complications is likely on the rise. Complications are well known to general clinicians, but are under-reported in the imaging literature. We present four cases of post-vaccination shoulder pain with magnetic resonance imaging (MRI) findings. An intrasubstance fluid-like signal in deep muscular and/or tendinous structures was the most common finding on MRI of these four cases. Focal bone marrow signal within the humeral head and inflammatory changes in the subacromial/subdeltoid bursa were also observed. The most likely reason for a humeral intraosseous edema-like signal was presumed injection of vaccine substance directly into osseous structures that might lead to focal osteitis. In the published literature, there is little emphasis on the imaging of local injection site complications accompanying influenza vaccination. We intended to increase familiarity of MRI findings in the setting of prolonged or severe clinical symptoms following influenza vaccination through the imaging findings of these four cases. (orig.)
Strutton David R
Full Text Available Abstract Background Influenza pandemic outbreaks occurred in the US in 1918, 1957, and 1968. Historical evidence suggests that the majority of influenza-related deaths during the 1918 US pandemic were attributable to bacterial pneumococcal infections. The 2009 novel influenza A (H1N1 outbreak highlights the importance of interventions that may mitigate the impact of a pandemic. Methods A decision-analytic model was constructed to evaluate the impact of 7-valent pneumococcal conjugate vaccine (PCV7 on pneumococcal disease incidence and mortality during a typical influenza season (13/100 and a severe influenza pandemic (30/100. Outcomes were compared for current PCV7 vaccination practices vs. no vaccination. The model was estimated using published sources and includes indirect (herd protection of non-vaccinated persons. Results The model predicts that PCV7 vaccination in the US is cost saving for a normal influenza season, reducing pneumococcal-related costs by $1.6 billion. In a severe influenza pandemic, vaccination would save $7.3 billion in costs and prevent 512,000 cases of IPD, 719,000 cases of pneumonia, 62,000 IPD deaths, and 47,000 pneumonia deaths; 84% of deaths are prevented due to indirect (herd protection in the unvaccinated. Conclusions PCV7 vaccination is highly effective and cost saving in both normal and severe pandemic influenza seasons. Current infant vaccination practices may prevent >1 million pneumococcal-related deaths in a severe influenza pandemic, primarily due to herd protection.
Rubin, Jaime L; McGarry, Lisa J; Klugman, Keith P; Strutton, David R; Gilmore, Kristen E; Weinstein, Milton C
Influenza pandemic outbreaks occurred in the US in 1918, 1957, and 1968. Historical evidence suggests that the majority of influenza-related deaths during the 1918 US pandemic were attributable to bacterial pneumococcal infections. The 2009 novel influenza A (H1N1) outbreak highlights the importance of interventions that may mitigate the impact of a pandemic. A decision-analytic model was constructed to evaluate the impact of 7-valent pneumococcal conjugate vaccine (PCV7) on pneumococcal disease incidence and mortality during a typical influenza season (13/100) and a severe influenza pandemic (30/100). Outcomes were compared for current PCV7 vaccination practices vs. no vaccination. The model was estimated using published sources and includes indirect (herd) protection of non-vaccinated persons. The model predicts that PCV7 vaccination in the US is cost saving for a normal influenza season, reducing pneumococcal-related costs by $1.6 billion. In a severe influenza pandemic, vaccination would save $7.3 billion in costs and prevent 512,000 cases of IPD, 719,000 cases of pneumonia, 62,000 IPD deaths, and 47,000 pneumonia deaths; 84% of deaths are prevented due to indirect (herd) protection in the unvaccinated. PCV7 vaccination is highly effective and cost saving in both normal and severe pandemic influenza seasons. Current infant vaccination practices may prevent >1 million pneumococcal-related deaths in a severe influenza pandemic, primarily due to herd protection.
Khan, Afshin Alaf; Varan, Aiden Kennedy; Esteves-Jaramillo, Alejandra; Siddiqui, Mariam; Sultana, Shazia; Ali, Asad S; Zaidi, Anita K M; Omer, Saad B
Facilitators and barriers to influenza vaccination among pregnant women in the developing world are poorly understood, particularly in South Asia. We assessed intention to accept influenza vaccine among ethnically diverse low-income pregnant women in Pakistan. From May to August 2013, we conducted a cross-sectional survey of pregnant women who visited health centers in urban slums in Karachi city. We assessed intention to accept influenza vaccine against socio-demographic factors, vaccination history, vaccine recommendation sources, and other factors. In an unvaccinated study population of 283 respondents, 87% were willing to accept the vaccine, if offered. All except two participants were aware of symptoms typically associated with influenza. Perceived vaccine safety, efficacy, and disease susceptibility were significantly associated with intention to accept influenza vaccine (p<0.05). Regardless of intention to accept influenza vaccine, 96% rated healthcare providers as highly reliable source of vaccine information. While a recommendation from a physician was critical for influenza vaccine acceptance, parents-in-law and husbands were often considered the primary decision-makers for pregnant women seeking healthcare including vaccination. Maternal influenza vaccination initiatives in South Asia should strongly consider counseling of key familial decision-makers and inclusion of healthcare providers to help implement new vaccination programs. Copyright © 2015 Elsevier Ltd. All rights reserved.
Holmes, Tyson H; He, Xiao-Song
Small, wide data sets are commonplace in human immunophenotyping research. As defined here, a small, wide data set is constructed by sampling a small to modest quantity n,1small, wide data sets. These prescriptions are distinctive in their especially heavy emphasis on minimizing the use of out-of-sample information for conducting statistical inference. This allows the working immunologist to proceed without being encumbered by imposed and often untestable statistical assumptions. Problems of unmeasured confounders, confidence-interval coverage, feature selection, and shrinkage/denoising are defined clearly and treated in detail. We propose an extension of an existing nonparametric technique for improved small-sample confidence-interval tail coverage from the univariate case (single immune feature) to the multivariate (many, possibly correlated immune features). An important role for derived features in the immunological interpretation of regression analyses is stressed. Areas of further research are discussed. Presented principles and methods are illustrated through application to a small, wide data set of adults spanning a wide range in ages and multiple immunophenotypes that were assayed before and after immunization with inactivated influenza vaccine (IIV). Our regression modeling prescriptions identify some potentially important topics for future immunological research. 1) Immunologists may wish to distinguish age-related differences in immune features from changes in immune features caused by aging. 2) A form of the bootstrap that employs linear extrapolation may prove to be an invaluable analytic tool because it allows the working immunologist to obtain accurate estimates of the stability of immune parameter estimates with a bare minimum of imposed assumptions. 3) Liberal inclusion of immune features in phenotyping panels can facilitate accurate separation of biological signal of interest from noise. In addition, through a combination of denoising and
Gefenaite, Giedre; Rahamat-Langendoen, Janette; Ambrozaitis, Arvydas; Mickiene, Aukse; Jancoriene, Ligita; Kuliese, Monika; Velyvyte, Daiva; Niesters, Hubert; Stolk, Ronald P.; Zagminas, Kestutis; Hak, Eelko
BACKGROUND: Due to scarce information on seasonal influenza vaccine effectiveness (SIVE) against severe clinical influenza outcomes in risk populations, we conducted a case-control study to assess its effects against laboratory-confirmed influenza in hospitalized patients during the 2012-2013
Orsi, Andrea; Colomba, Giuseppina Maria Elena; Pojero, Fanny; Calamusa, Giuseppe; Alicino, Cristiano; Trucchi, Cecilia; Canepa, Paola; Ansaldi, Filippo; Vitale, Francesco; Tramuto, Fabio
Influenza A and B viruses are responsible for respiratory infections, representing globally seasonal threats to human health. The 2 viral types often co-circulate and influenza B plays an important role in the spread of infection. A 6-year retrospective surveillance study was conducted between 2010 and 2016 in 2 large administrative regions of Italy, located in the north (Liguria) and in the south (Sicily) of the country, to describe the burden and epidemiology of both B/Victoria and B/Yamagata lineages in different healthcare settings. Influenza B viruses were detected in 5 of 6 seasonal outbreaks, exceeding influenza A during the season 2012-2013. Most of influenza B infections were found in children aged ≤ 14 y and significant differences were observed in the age-groups infected by the different lineages. B/Victoria strains prevailed in younger population than B/Yamagata, but also were more frequently found in the community setting. Conversely, B/Yamagata viruses were prevalent among hospitalized cases suggesting their potential role in the development of more severe disease. The relative proportions of viral lineages varied from year to year, resulting in different lineage-level mismatch for the B component of trivalent influenza vaccine. Our findings confirmed the need for continuous virological surveillance of seasonal epidemics and bring attention to the adoption of universal influenza immunization program in the childhood. The use of tetravalent vaccine formulations may be useful to improve the prevention and control of the influenza burden in general population.
Looijmans - van den Akker, I.
General introduction: To prevent influenza virus infection, immunization against influenza has been recommended for individuals with increased risk of complications. These groups comprise individuals of 60 years and older, individuals with risk-elevating co-morbid conditions, residents of nursing
Riphagen-Dalhuisen, Josien; Gefenaite, Giedre; Hak, Eelko
Objective Vaccinating healthcare workers (HCWs) against influenza is one of the most important methods of decreasing influenza transmission among at-risk patients in healthcare facilities. However, despite recommendations, the rate of uptake of influenza vaccine among HCWs remains low. The objective
Hak, E; Buskens, E; Nichol, K L; Verheij, T J M
It is unknown whether a first influenza vaccination protects high-risk adults from severe morbidity and mortality during influenza epidemics. As part of the PRISMA nested case-control study, we aimed to evaluate the effectiveness of first-time and repeat influenza vaccinations in adult persons
Peltola, Heikki; 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. PMID:25340259
Large-scale prevention by influenza vaccination aims at reducing post-influenza complications among those who need it at most. This thesis aims at describing the risk of complications and benefits of vaccination. In chapter 2 we determine prognostic factors for influenza-associated
Christensen, Dennis; Christensen, Jan P.; Korsholm, Karen S.
Influenza epidemics occur annually, and estimated 5-10% of the adult population and 20-30% of children will become ill from influenza infection. Seasonal vaccines primarily work through the induction of neutralizing antibodies against the principal surface antigen hemagglutinin (HA). This important...... role of HA-specific antibodies explains why previous pandemics have emerged when new HAs have appeared in circulating human viruses. It has long been recognized that influenza virus-specific CD4(+) T cells are important in protection from infection through direct effector mechanisms or by providing...... help to B cells and CD8(+) T cells. However, the seasonal influenza vaccine is poor at inducing CD4(+) T-cell responses and needs to be combined with an adjuvant facilitating this response. In this study, we applied the ferret model to investigate the cross-protective efficacy of a heterologous...
Wang, Tiffany L; Jing, Ling; Bocchini, Joseph A
As healthcare-associated influenza is a serious public health concern, this review examines legal and ethical arguments supporting mandatory influenza vaccination policies for healthcare personnel, implementation issues and evidence of effectiveness. Spread of influenza from healthcare personnel to patients can result in severe harm or death. Although most healthcare personnel believe that they should be vaccinated against seasonal influenza, the Centers for Disease Control and Prevention (CDC) report that only 79% of personnel were vaccinated during the 2015-2016 season. Vaccination rates were as low as 44.9% in institutions that did not promote or offer the vaccine, compared with rates of more than 90% in institutions with mandatory vaccination policies. Policies that mandate influenza vaccination for healthcare personnel have legal and ethical justifications. Implementing such policies require multipronged approaches that include education efforts, easy access to vaccines, vaccine promotion, leadership support and consistent communication emphasizing patient safety. Mandatory influenza vaccination for healthcare personnel is a necessary step in protecting patients. Patients who interact with healthcare personnel are often at an elevated risk of complications from influenza. Vaccination is the best available strategy for protecting against influenza and evidence shows that institutional policies and state laws can effectively increase healthcare personnel vaccination rates, decreasing the risk of transmission in healthcare settings. There are legal and ethical precedents for institutional mandatory influenza policies and state laws, although successful implementation requires addressing both administrative and attitudinal barriers.
... doctors' offices, clinics, State and local health departments, pharmacies, college and university health... private health plans have no co-payment or deductible for influenza vaccinations. While the flu can make... complications from the flu. Pregnant women, young children, older adults, as well as people living with HIV...
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…
Hotez, Peter J; Diemert, David; Bacon, Kristina M; Beaumier, Coreen; Bethony, Jeffrey M; Bottazzi, Maria Elena; Brooker, Simon; Couto, Artur Roberto; Freire, Marcos da Silva; Homma, Akira; Lee, Bruce Y; Loukas, Alex; Loblack, Marva; Morel, Carlos Medicis; Oliveira, Rodrigo Correa; Russell, Philip K
Hookworm infection is one of the world's most common neglected tropical diseases and a leading cause of iron deficiency anemia in low- and middle-income countries. A Human Hookworm Vaccine is currently being developed by the Sabin Vaccine Institute and is in phase 1 clinical testing. The candidate vaccine is comprised of two recombinant antigens known as Na-GST-1 and Na-APR-1, each of which is an important parasite enzyme required for hookworms to successfully utilize host blood as a source of energy. The recombinant proteins are formulated on Alhydrogel(®) and are being tested in combination with a synthetic Toll-like receptor 4 agonist. The aim of the vaccine is to induce anti-enzyme antibodies that will reduce both host blood loss and the number of hookworms attached to the gut. Transfer of the manufacturing technology to the Oswaldo Cruz Foundation (FIOCRUZ)/Bio-Manguinhos (a Brazilian public sector developing country vaccine manufacturer) is planned, with a clinical development plan that could lead to registration of the vaccine in Brazil. The vaccine would also need to be introduced in the poorest regions of Africa and Asia, where hookworm infection is highly endemic. Ultimately, the vaccine could become an essential tool for achieving hookworm control and elimination, a key target in the 2012 London Declaration on Neglected Tropical Diseases. Copyright © 2012 Elsevier Ltd. All rights reserved.
Underwood, Natasha L; Weiss, Paul; Gargano, Lisa M; Seib, Katherine; Rask, Kimberly J; Morfaw, Christopher; Murray, Dennis; DiClemente, Ralph J; Hughes, James M; Sales, Jessica M
Human papillomavirus (HPV) vaccination coverage for adolescent females and males remains low in the United States. We conducted a 3-arm randomized controlled trial (RCT) conducted in middle and high schools in eastern Georgia from 2011-2013 to determine the effect of 2 educational interventions used to increase adolescent vaccination coverage for the 4 recommended adolescent vaccines: Tdap, MCV4, HPV and influenza. As part of this RCT, this article focuses on: 1) describing initiation and completion of HPV vaccine series among a diverse population of male and female adolescents; 2) assessing parental attitudes toward HPV vaccine; and 3) examining correlates of HPV vaccine series initiation and completion. Parental attitude score was the strongest predictor of HPV vaccine initiation among adolescents (adjusted odds ratio (aOR): 2.08; 95% confidence interval (CI): 1.80, 2.39). Other correlates that significantly predicted HPV series initiation were gender, study year, and intervention arm. Parental attitudes remained a significant predictor of receipt of 3 doses of HPV vaccine along with gender, race, school type and insurance type. This study demonstrates that positive parental attitudes are important predictors of HPV vaccination and critical to increasing coverage rates. Our findings suggest that more research is needed to understand how parental attitudes are developed and evolve over time.
Sowden, Evin; Mitchell, William S
Influenza and pneumococcal vaccination are recommended for a number of clinical risk groups including patients treated with major immunosuppressant disease modifying anti-rheumatic drugs. Such immunisation is not only safe but immunogenic in patients with rheumatic diseases. We sought to establish dual vaccination rates and significant influencing factors amongst our hospital rheumatology outpatients. We audited a sample of 101 patients attending hospital rheumatology outpatient clinics on any form of disease modifying treatment by clinical questionnaire and medical record perusal. Further data were collected from the local immunisation coordinating agency and analysed by logistic regression modelling. Although there was a high rate of awareness with regard to immunisation, fewer patients on major immunosuppressants were vaccinated than patients with additional clinical risk factors against influenza (53% vs 93%, p risk factors was confirmed as significant in determining vaccination status by logistic regression for both influenza (OR 10.89, p < 0.001) and streptococcus pneumoniae (OR 4.55, p = 0.002). The diagnosis of rheumatoid arthritis was also found to be a significant factor for pneumococcal vaccination (OR 5.1, p = 0.002). There was a negative trend suggesting that patients on major immunosuppressants are less likely to be immunised against pneumococcal antigen (OR 0.35, p = 0.067). Influenza and pneumococcal immunisation is suboptimal amongst patients on current immunosuppressant treatments attending rheumatology outpatient clinics. Raising awareness amongst patients may not be sufficient to improve vaccination rates and alternative strategies such as obligatory pneumococcal vaccination prior to treatment initiation and primary care provider education need to be explored.
Dimitrios G Koutsonanos
Full Text Available 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.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 x LD(50 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.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 novel and highly effective immunization method.
Aka Akt?rk, ?lk?; G?rek Dilekta?l?, Asl?; ?eng?l, Aysun; Musaffa Salep?i, Banu; Oktay, Nuray; D?ger, Mustafa; Ar?k Ta?y?kan, Hale; Durmu? Ko?ak, Nagihan
Background: Influenza and pneumococcal vaccinations are recommended in chronic obstructive pulmonary disease patients to decrease associated risks at all stages. Although the prevalence of chronic obstructive pulmonary disease is high in our country, as previously reported, vaccination rates are low. Aims: To assess the vaccination rates of chronic obstructive pulmonary disease patients and factors that may affect these. Study Design: Multi-centre cross-sectional study. Methods: Patients admi...
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…
effectiveness: Maintained protection throughout the duration of influenza seasons 2010–2011 through 2013–2014http://dx.doi.org/10.1016/j.vaccine...Unfortunately, we did not have data on the proportion who received the higher-dose vaccine. Another limitation of our study is that we did not conduct a...significant protection against influenza infection for the duration of the influenza season or up to 6 months postvac- cination. Since the start of the
Lidewij C. M. Wiersma
Full Text Available 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.
Mitchell William S
Full Text Available Abstract Background Influenza and pneumococcal vaccination are recommended for a number of clinical risk groups including patients treated with major immunosuppressant disease modifying anti-rheumatic drugs. Such immunisation is not only safe but immunogenic in patients with rheumatic diseases. We sought to establish dual vaccination rates and significant influencing factors amongst our hospital rheumatology outpatients. Method We audited a sample of 101 patients attending hospital rheumatology outpatient clinics on any form of disease modifying treatment by clinical questionnaire and medical record perusal. Further data were collected from the local immunisation coordinating agency and analysed by logistic regression modelling. Results Although there was a high rate of awareness with regard to immunisation, fewer patients on major immunosuppressants were vaccinated than patients with additional clinical risk factors against influenza (53% vs 93%, p Conclusion Influenza and pneumococcal immunisation is suboptimal amongst patients on current immunosuppressant treatments attending rheumatology outpatient clinics. Raising awareness amongst patients may not be sufficient to improve vaccination rates and alternative strategies such as obligatory pneumococcal vaccination prior to treatment initiation and primary care provider education need to be explored.
Benefits, harms, costs. Successful vaccination may be effective. in protecting against acute respiratory tract infection, and preventing hospitalisation, complicating pneumonia and death. The vaccine is safe with only occasional reports of anaphylaxis. Contraindications to the vaccine are anaphylactic hypersensitivity to eggs, ...
Vaccines play a critical role in the poultry industries efforts at disease control and prevention. However, providing safe, efficacious, and cost-effective vaccines remains a constant issue to the industry. In addition, many viruses undergo mutation in the field requiring vaccine adjustments. Recent...
Remschmidt, Cornelius; Wichmann, Ole; Harder, Thomas
There is a growing body of evidence on the risks and benefits of influenza vaccination in various target groups. Systematic reviews are of particular importance for policy decisions. However, their methodological quality can vary considerably. To investigate the methodological quality of systematic reviews on influenza vaccination (efficacy, effectiveness, safety) and to identify influencing factors. A systematic literature search on systematic reviews on influenza vaccination was performed, using MEDLINE, EMBASE and three additional databases (1990-2013). Review characteristics were extracted and the methodological quality of the reviews was evaluated using the assessment of multiple systematic reviews (AMSTAR) tool. U-test, Kruskal-Wallis test, chi-square test, and multivariable linear regression analysis were used to assess the influence of review characteristics on AMSTAR-score. Fourty-six systematic reviews fulfilled the inclusion criteria. Average methodological quality was high (median AMSTAR-score: 8), but variability was large (AMSTAR range: 0-11). Quality did not differ significantly according to vaccination target group. Cochrane reviews had higher methodological quality than non-Cochrane reviews (p=0.001). Detailed analysis showed that this was due to better study selection and data extraction, inclusion of unpublished studies, and better reporting of study characteristics (all p<0.05). In the adjusted analysis, no other factor, including industry sponsorship or journal impact factor had an influence on AMSTAR score. Systematic reviews on influenza vaccination showed large differences regarding their methodological quality. Reviews conducted by the Cochrane collaboration were of higher quality than others. When using systematic reviews to guide the development of vaccination recommendations, the methodological quality of a review in addition to its content should be considered. Copyright © 2014 Elsevier Ltd. All rights reserved.
Bragstad, Karoline; Vinner, Lasse; Hansen, Mette Sif
seasonal and emerging influenza viruses. We have developed an alternative influenza vaccine based on DNA expressing selected influenza proteins of pandemic and seasonal origin. In the current study, we investigated the protection of a polyvalent influenza DNA vaccine approach in pigs. We immunised pigs...... intradermally with a combination of influenza DNA vaccine components based on the pandemic 1918 H1N1 (M and NP genes), pandemic 2009 H1N1pdm09 (HA and NA genes) and seasonal 2005 H3N2 genes (HA and NA genes) and investigated the protection against infection with virus both homologous and heterologous to the DNA...... of this DNA vaccine to limit virus shedding may have an impact on virus spread among pigs which could possibly extend to humans as well, thereby diminishing the risk for epidemics and pandemics to evolve....
... Exclusive License: Avian Influenza Vaccines for Domesticated Poultry/Wild Birds To Be Provided to the... serotypes H5N1, H1N1, H3N2, and H3N8 for poultry, swine and equine. Particularly one vaccine, a trivalent... influenza vaccines are specifically designed for poultry, swine and equine recipients, with the following...
Full Text Available This article presents the safety data for cell-derived inactivated subunit adjuvanted influenza vaccine «Grippol Neo» in children 3–17 years old in comparison with reference egg-derived inactivated subunit vaccine «Grippol plus». Good test vaccine tolerability and high efficacy profile is demonstrated. Based on the results obtained vaccine «Grippol Neo» is recommended for mass influenza prophylaxis in pediatry, including National Immunization Schedule.Key words: children, influenza, vaccination, «Grippol Neo».(Voprosy sovremennoi pediatrii — Current Pediatrics. – 2010;9(4:44-49
Background Routine annual influenza vaccination is primarily recommended for all persons aged 60 and above and for people with underlying chronic conditions in Germany. Other countries have already adopted additional childhood influenza immunisation programmes. The objective of this study is to determine the potential epidemiological impact of implementing paediatric influenza vaccination using intranasally administered live-attenuated influenza vaccine (LAIV) in Germany. Methods A deterministic age-structured model is used to simulate the population-level impact of different vaccination strategies on the transmission dynamics of seasonal influenza in Germany. In our base-case analysis, we estimate the effects of adding a LAIV-based immunisation programme targeting children 2 to 17 years of age to the existing influenza vaccination policy. The data used in the model is based on published evidence complemented by expert opinion. Results In our model, additional vaccination of children 2 to 17 years of age with LAIV leads to the prevention of 23.9 million influenza infections and nearly 16 million symptomatic influenza cases within 10 years. This reduction in burden of disease is not restricted to children. About one third of all adult cases can indirectly be prevented by LAIV immunisation of children. Conclusions Our results demonstrate that vaccinating children 2–17 years of age is likely associated with a significant reduction in the burden of paediatric influenza. Furthermore, annual routine childhood vaccination against seasonal influenza is expected to decrease the incidence of influenza among adults and older people due to indirect effects of herd protection. In summary, our model provides data supporting the introduction of a paediatric influenza immunisation programme in Germany. PMID:24450996
Yang, Huanliang; Chen, Yan; Shi, Jianzhong; Guo, Jing; Xin, Xiaoguang; Zhang, Jian; Wang, Dayan; Shu, Yuelong; Qiao, Chuanling; Chen, Hualan
Influenza A (H1N1) virus has caused human influenza outbreaks in a worldwide pandemic since April 2009. Pigs have been found to be susceptible to this influenza virus under experimental and natural conditions, raising concern about their potential role in the pandemic spread of the virus. In this study, we generated a high-growth reassortant virus (SC/PR8) that contains the hemagglutinin (HA) and neuraminidase (NA) genes from a novel H1N1 isolate, A/Sichuan/1/2009 (SC/09), and six internal genes from A/Puerto Rico/8/34 (PR8) virus, by genetic reassortment. The immunogenicity and protective efficacy of this reassortant virus were evaluated at different doses in a challenge model using a homologous SC/09 or heterologous A/Swine/Guangdong/1/06(H1N2) virus (GD/06). Two doses of SC/PR8 virus vaccine elicited high-titer serum hemagglutination inhibiting (HI) antibodies specific for the 2009 H1N1 virus and conferred complete protection against challenge with either SC/09 or GD/06 virus, with reduced lung lesions and viral shedding in vaccine-inoculated animals compared with non-vaccinated control animals. These results indicated for the first time that a high-growth SC/PR8 reassortant H1N1 virus exhibits properties that are desirable to be a promising vaccine candidate for use in swine in the event of a pandemic H1N1 influenza. Copyright © 2011 Elsevier B.V. All rights reserved.
Lee, Laurel Yong-Hwa; Anh, Ha Do Lien; Simmons, Cameron; de Jong, Menno D.; Chau, Nguyen Van Vinh; Schumacher, Reto; Peng, Yan Chun; McMichael, Andrew J.; Farrar, Jeremy J.; Smith, Geoffrey L.; Townsend, Alain R. M.; Askonas, Brigitte A.; Rowland-Jones, Sarah; Dong, Tao
The threat of avian influenza A (H5N1) infection in humans remains a global health concern. Current influenza vaccines stimulate antibody responses against the surface glycoproteins but are ineffective against strains that have undergone significant antigenic variation. An alternative approach is to
Full Text Available INTRODUCTION: The 2011-12 trivalent influenza vaccine contains a strain of influenza B/Victoria-lineage viruses. Despite free provision of influenza vaccine among target populations, an epidemic predominated by influenza B/Yamagata-lineage viruses occurred during the 2011-12 season in Taiwan. We characterized this vaccine-mismatched epidemic and estimated influenza vaccine effectiveness (VE. METHODS: Influenza activity was monitored through sentinel viral surveillance, emergency department (ED and outpatient influenza-like illness (ILI syndromic surveillance, and case-based surveillance of influenza with complications and deaths. VE against laboratory-confirmed influenza was evaluated through a case-control study on ILI patients enrolled into sentinel viral surveillance. Logistic regression was used to estimate VE adjusted for confounding factors. RESULTS: During July 2011-June 2012, influenza B accounted for 2,382 (72.5% of 3,285 influenza-positive respiratory specimens. Of 329 influenza B viral isolates with antigen characterization, 287 (87.2% were B/Yamagata-lineage viruses. Proportions of ED and outpatient visits being ILI-related increased from November 2011 to January 2012. Of 1,704 confirmed cases of influenza with complications, including 154 (9.0% deaths, influenza B accounted for 1,034 (60.7% of the confirmed cases and 103 (66.9% of the deaths. Reporting rates of confirmed influenza with complications and deaths were 73.5 and 6.6 per 1,000,000, respectively, highest among those aged ≥65 years, 50-64 years, 3-6 years, and 0-2 years. Adjusted VE was -31% (95% CI: -80, 4 against all influenza, 54% (95% CI: 3, 78 against influenza A, and -66% (95% CI: -132, -18 against influenza B. CONCLUSIONS: This influenza epidemic in Taiwan was predominated by B/Yamagata-lineage viruses unprotected by the 2011-12 trivalent vaccine. The morbidity and mortality of this vaccine-mismatched epidemic warrants careful consideration of introducing a
VE) and findings are shared annually at the Food and Drug Administration’s advisory committee meet- ing on U.S. influenza vaccine strain selec- tion...Aeromedical Services Information Manage - ment System) and self-report from patient questionnaires. Individuals were consid- ered vaccinated if they received...surveillance are used to estimate midseason influenza vaccine effectiveness (VE) and findings are shared annually at the Food and Drug
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 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 suggested decrease in influenza VE with time since vaccination was mostly observed in the elderly population. The decreasing protective effect of the vaccine in the late part of the season could be related to waning vaccine protection because no viral changes were identified throughout the season. PMID:24053661
Abu-Rish, Eman Y; Elayeh, Eman R; Mousa, Lubabah A; Butanji, Yasser K; Albsoul-Younes, Abla M
Influenza is an underestimated contributor to morbidity and mortality. Population knowledge regarding influenza and its vaccination has a key role in enhancing vaccination coverage. This study aimed to identify the gaps of knowledge among Jordanian population towards influenza and its vaccine, and to identify the major determinants of accepting seasonal influenza vaccine in adults and children in Jordan. This was a cross-sectional study that enrolled 941 randomly selected adults in Amman, Jordan. A four-section questionnaire was used which included questions about the sociodemographic characteristics, knowledge about influenza and the factors that affect seasonal influenza vaccine acceptance and refusal. Only 47.3% of the participants were considered knowledgeable. About half of the participants (51.9%) correctly identified the main influenza preventative measures. Lack of knowledge about the important role of seasonal influenza vaccine in disease prevention was observed. Low vaccination rate (20% of adults) was reported. The most critical barrier against vaccination in adults and children was the concern about the safety and the efficacy of the vaccine, while the most important predictors for future vaccination in adults and children were physician recommendation and government role. In children, the inclusion of the vaccine within the national immunization program was an important determinant of vaccine acceptance. Formulating new strategies to improve the population's level of knowledge, assuring the population about the safety and the efficacy of the vaccine and the inclusion of the vaccine within the national immunization program are the essential factors to enhance vaccination coverage in Jordan. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: email@example.com.
Salmon, Daniel A.; Akhtar, Aysha; Mergler, Michelle J.; Vannice, Kirsten S.; Izurieta, Hector; Ball, Robert; Lee, Grace M.; Vellozzi, Claudia; Garman, Patrick; Cunningham, Francesca; Gellin, Bruce; Koh, Howard; Lurie, Nicole
The effort to vaccinate the US population against the 2009 H1N1 influenza virus hinged, in part, on public confidence in vaccine safety. Early in the vaccine program, >20% of parents reported that they would not vaccinate their children. Concerns about the safety of the vaccines were reported by
Breukels, M. A.; Spanjaard, L.; Sanders, L. A.; Rijkers, G. T.
Infant vaccination with conjugated Haemophilus influenzae type b (Hib) vaccine is highly effective in protecting against invasive Hib infections, but vaccine failures do occur. Twenty-one vaccine failures are reported since the introduction of the Hib conjugate vaccine in The Netherlands. Of the 14
Full Text Available Sustained outbreaks of highly pathogenic avian influenza (HPAI H5N1 in avian species increase the risk of reassortment and adaptation to humans. The ability to contain its spread in chickens would reduce this threat and help maintain the capacity for egg-based vaccine production. While vaccines offer the potential to control avian disease, a major concern of current vaccines is their potency and inability to protect against evolving avian influenza viruses.The ability of DNA vaccines encoding hemagglutinin (HA proteins from different HPAI H5N1 serotypes was evaluated for its ability to elicit neutralizing antibodies and to protect against homologous and heterologous HPAI H5N1 strain challenge in mice and chickens after DNA immunization by needle and syringe or with a pressure injection device. These vaccines elicited antibodies that neutralized multiple strains of HPAI H5N1 when given in combinations containing up to 10 HAs. The response was dose-dependent, and breadth was determined by the choice of the influenza virus HA in the vaccine. Monovalent and trivalent HA vaccines were tested first in mice and conferred protection against lethal H5N1 A/Vietnam/1203/2004 challenge 68 weeks after vaccination. In chickens, protection was observed against heterologous strains of HPAI H5N1 after vaccination with a trivalent H5 serotype DNA vaccine with doses as low as 5 microg DNA given twice either by intramuscular needle injection or with a needle-free device.DNA vaccines offer a generic approach to influenza virus immunization applicable to multiple animal species. In addition, the ability to substitute plasmids encoding different strains enables rapid adaptation of the vaccine to newly evolving field isolates.
Mills, Kimberly L; Jin, Hong; Duke, Greg; Lu, Bin; Luke, Catherine J; Murphy, Brian; Swayne, David E; Kemble, George; Subbarao, Kanta
Background Recent outbreaks of highly pathogenic influenza A H5N1 viruses in humans and avian species that began in Asia and have spread to other continents underscore an urgent need to develop vaccines that would protect the human population in the event of a pandemic. Methods and Findings Live, attenuated candidate vaccines possessing genes encoding a modified H5 hemagglutinin (HA) and a wild-type (wt) N1 neuraminidase from influenza A H5N1 viruses isolated in Hong Kong and Vietnam in 1997, 2003, and 2004, and remaining gene segments derived from the cold-adapted (ca) influenza A vaccine donor strain, influenza A/Ann Arbor/6/60 ca (H2N2), were generated by reverse genetics. The H5N1 ca vaccine viruses required trypsin for efficient growth in vitro, as predicted by the modification engineered in the gene encoding the HA, and possessed the temperature-sensitive and attenuation phenotypes specified by the internal protein genes of the ca vaccine donor strain. More importantly, the candidate vaccines were immunogenic in mice. Four weeks after receiving a single dose of 106 50% tissue culture infectious doses of intranasally administered vaccines, mice were fully protected from lethality following challenge with homologous and antigenically distinct heterologous wt H5N1 viruses from different genetic sublineages (clades 1, 2, and 3) that were isolated in Asia between 1997 and 2005. Four weeks after receiving two doses of the vaccines, mice and ferrets were fully protected against pulmonary replication of homologous and heterologous wt H5N1 viruses. Conclusions The promising findings in these preclinical studies of safety, immunogenicity, and efficacy of the H5N1 ca vaccines against antigenically diverse H5N1 vaccines provide support for their careful evaluation in Phase 1 clinical trials in humans. PMID:16968127
Amorsolo L Suguitan
Full Text Available Recent outbreaks of highly pathogenic influenza A H5N1 viruses in humans and avian species that began in Asia and have spread to other continents underscore an urgent need to develop vaccines that would protect the human population in the event of a pandemic.Live, attenuated candidate vaccines possessing genes encoding a modified H5 hemagglutinin (HA and a wild-type (wt N1 neuraminidase from influenza A H5N1 viruses isolated in Hong Kong and Vietnam in 1997, 2003, and 2004, and remaining gene segments derived from the cold-adapted (ca influenza A vaccine donor strain, influenza A/Ann Arbor/6/60 ca (H2N2, were generated by reverse genetics. The H5N1 ca vaccine viruses required trypsin for efficient growth in vitro, as predicted by the modification engineered in the gene encoding the HA, and possessed the temperature-sensitive and attenuation phenotypes specified by the internal protein genes of the ca vaccine donor strain. More importantly, the candidate vaccines were immunogenic in mice. Four weeks after receiving a single dose of 10(6 50% tissue culture infectious doses of intranasally administered vaccines, mice were fully protected from lethality following challenge with homologous and antigenically distinct heterologous wt H5N1 viruses from different genetic sublineages (clades 1, 2, and 3 that were isolated in Asia between 1997 and 2005. Four weeks after receiving two doses of the vaccines, mice and ferrets were fully protected against pulmonary replication of homologous and heterologous wt H5N1 viruses.The promising findings in these preclinical studies of safety, immunogenicity, and efficacy of the H5N1 ca vaccines against antigenically diverse H5N1 vaccines provide support for their careful evaluation in Phase 1 clinical trials in humans.
Clayton, Joshua L; Potter, Rachel C; Wells, Eden V; Carlton, Cristi A; Boulton, Matthew L
Influenza vaccination for all children aged 6 months to 18 years has been recommended since 2008 to prevent flu-related morbidity and mortality. However, 2010-2011 influenza vaccine coverage estimates show under-vaccination in children of all ages. We examined predictors of influenza vaccination in Michigan during the 2010-2011 influenza season. To determine whether immunization provider type was associated with a child's influenza vaccination in Michigan and assess whether county-level factors were confounders of the association. Influenza vaccinations reported to the Michigan Care Improvement Registry from the 2010-2011 influenza season were analyzed in 2012 to estimate ORs for the association between immunization provider type and influenza vaccination. Among 2,373,826 Michigan children aged 6 months through 17 years, 17% were vaccinated against influenza and lower vaccination rates were observed for public compared to private providers (13% vs 18%). In the unadjusted model, public providers had lower odds of vaccinating children compared to private providers (OR=0.60, 95% CI=0.60, 0.61). County-level factors, including percentage of families living below the poverty line, median household income, and percentage black race, were not shown to confound the association. In the adjusted models, public providers had lower odds of vaccinating children compared to private providers (OR=0.87, 95% CI=0.86, 0.88). Although a child's likelihood of influenza vaccination in Michigan varies by provider type, more effective strategies to improve influenza vaccination rates for all Michigan children are needed. Copyright © 2014 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.
Newes-Adeyi, Gabriella; Greece, Jacey; Bozeman, Sam; Walker, Deborah Klein; Lewis, Faith; Gidudu, Jane
We conducted a pilot study of the Integrated Vaccine Surveillance System (IVSS), a novel active surveillance system for monitoring influenza vaccine adverse events that could be used in mass vaccination settings. We recruited 605 adult vaccinees from a convenience sample of 12 influenza vaccine clinics conducted by public health departments of two U.S. metropolitan regions. Vaccinees provided daily reports on adverse reactions following immunization (AEFI) using an interactive voice response system (IVR) or the internet for 14 consecutive days following immunization. Followup with nonrespondents was conducted through computer-assisted telephone interviewing (CATI). Data on vaccinee reports were available real-time through a dedicated secure website. 90% (545) of vaccinees made at least one daily report and 49% (299) reported consecutively for the full 14-day period. 58% (315) used internet, 20% (110) IVR, 6% (31) CATI, and 16% (89) used a combination for daily reports. Of the 545 reporters, 339 (62%) reported one or more AEFI, for a total of 594 AEFIs reported. The majority (505 or 85%) of these AEFIs were mild symptoms. It is feasible to develop a system to obtain real-time data on vaccine adverse events. Vaccinees are willing to provide daily reports for a considerable time post vaccination. Offering multiple modes of reporting encourages high response rates. Study findings on AEFIs showed that the IVSS was able to exhibit the emerging safety profile of the 2008 seasonal influenza vaccine. Copyright © 2011 Elsevier Ltd. All rights reserved.
Jackson, Michael L.; Jackson, Lisa A.; Kieke, Burney; McClure, David; Gaglani, Manjusha; Murthy, Kempapura; Malosh, Ryan; Monto, Arnold; Zimmerman, Richard K.; Foppa, Ivo M.; Flannery, Brendan; Thompson, Mark G.
Background We estimated the burden of outpatient influenza and cases prevented by vaccination during the 2011/12 and 2012/13 influenza seasons using data from the United States Influenza Vaccine Effectiveness (US Flu VE) Network. Methods We defined source populations of persons who could seek care for acute respiratory illness (ARI) at each of the five US Flu VE Network sites. We identified all members of the source population who were tested for influenza during US Flu VE influenza surveillance. Each influenza-positive subject received a sampling weight based on the proportion of source population members who were tested for influenza, stratified by site, age, and other factors. We used the sampling weights to estimate the cumulative incidence of medically attended influenza in the source populations. We estimated cases averted by vaccination using estimates of cumulative incidence, vaccine coverage, and vaccine effectiveness. Results Cumulative incidence of medically attended influenza ranged from 0.8% to 2.8% across sites during 2011/12 and from 2.6% to 6.5% during the 2012/13 season. Stratified by age, incidence ranged from 1.2% among adults 50 years of age and older in 2011/12 to 10.9% among children 6 months to 8 years of age in 2012/13. Cases averted by vaccination ranged from 4 to 41 per 1,000 vaccinees, depending on the study site and year. Conclusions The incidence of medically attended influenza varies greatly by year and even by geographic region within the same year. The number of cases averted by vaccination varies greatly based on overall incidence and on vaccine coverage. PMID:26271827
Antón, F; Richart, M J; Serrano, S; Martínez, A M; Pruteanu, D F
Vaccination coverage reached in adults is insufficient, and there is a real need for new strategies. To compare strategies for improving influenza vaccination coverage in persons older than 64 years. New strategies were introduced in our health care centre during 2013-2014 influenza vaccination campaign, which included vaccinating patients in homes for the aged as well as in the health care centre. A comparison was made on vaccination coverage over the last 4 years in 3 practices of our health care centre: P1, the general physician vaccinated patients older than 64 that came to the practice; P2, the general physician systematically insisted in vaccination in elderly patients, strongly advising to book appointments, and P3, the general physician did not insist. These practices looked after P1: 278; P2: 320; P3: 294 patients older than 64 years. Overall/P1/P2/P3 coverages in 2010: 51.2/51.4/55/46.9% (P=NS), in 2011: 52.4/52.9/53.8/50.3% (P=NS), in 2012: 51.9/52.5/55.3/47.6% (P=NS), and in 2013: 63.5/79.1/59.7/52.7 (P=.000, P1 versus P2 and P3; P=NS between P2 and P3). Comparing the coverages in 2012-2013 within each practice P1 (P=.000); P2 (P=.045); P3 (P=.018). In P2 and P3 all vaccinations were given by the nurses as previously scheduled. In P3, 55% of the vaccinations were given by the nurses, 24.1% by the GP, 9.7% rejected vaccination, and the remainder did not come to the practice during the vaccination period (October 2013-February 2014). The strategy of vaccinating in the homes for the aged improved the vaccination coverage by 5% in each practice. The strategy of "I've got you here, I jab you here" in P1 improved the vaccination coverage by 22%. Copyright © 2014 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.
Capua, I; Cattoli, G
Vaccination against avian influenza is recommended as a tool to support control measures in countries affected by avian influenza. Vaccination is known to increase the resistance of susceptible birds to infection and also to reduce shedding; however, it does not always prevent infection. Vaccinated infected flocks can therefore be a source of infection and thus be responsible for the perpetuation of infection. To avoid the spread of infection in a vaccinated population, immunization strategies must allow differentiation of infected from vaccinated animals (DIVA), combined with an appropriate monitoring system. Vaccinated exposed flocks must be identified and managed by restriction policies that include controlled marketing and stamping-out. Several vaccines and diagnostic tests to detect infection in vaccinated populations are available, the tests having various properties and characteristics. In order to achieve eradication, the most appropriate DIVA vaccination strategy must be identified and an appropriate monitoring programme be designed, taking into account risk factors, the epidemiological situation and the socioeconomic implications of the policy.
Full Text Available Abstract Background The unpredictable nature of the potentially devastating impact of 2009 pH1N1 influenza pandemic highlights the need for pandemic preparedness planning, where modeling studies could be most useful for simulations of possible future scenarios. Methods A compartmental model with pre-symptomatic and asymptomatic influenza infections is proposed which incorporates age groups as well as intervention measures such as age-specific vaccination, in order to study spread of influenza in a community. Results We derive the basic reproduction number and other effective reproduction numbers under various intervention measures. For illustration, we make use of the Pneumonia and Influenza (P&I mortality data and vaccination data of the very young (age 0-2 and the very old (age >64 during 2004-2005 Taiwan winter influenza season to fit our model and to compute the relevant reproduction numbers. The reproduction number for this winter flu season is estimated to be slightly above one (~1.0001. Conclusions Comparatively large errors in fitting the P&I mortality data of the elderly (>64 were observed shortly after winter school closings in January, which may indicate the impact of younger, more active age groups transmitting influenza to other age groups outside of the school settings; in particular, to the elderly in the households. Pre-symptomatic infections seemed to have little effect on the model fit, while asymptomatic infection by asymptomatic infectives has a more pronounced impact on the model fit for the elderly mortality, perhaps indicating a larger role in disease transmission by asymptomatic infection. Simulations indicate that the impact of vaccination on the disease incidence might not be fully revealed in the change (or the lack thereof in the effective reproduction number with interventions, but could still be substantial. The estimated per contact transmission probability for susceptible elderly is significantly higher than that
Mollard, Elizabeth K; Guenzel, Nicholas; Brown, Peggy A; Keeler, Heidi J; Cramer, Mary E
Influenza exposure during pregnancy can cause severe health problems for both the mother and her offspring, including an increased risk of mortality. Influenza vaccination during all trimesters of pregnancy is safe and effective, and recommended by professional organizations such as the American College of Obstetrics and Gynecology. Despite these recommendations, the U.S. vaccination rates remain low in this high-risk population. A policy analysis based on the five-part method identified by Teitelbaum and Wilensky () addresses factors to consider in identifying the best voluntary policy options to improve the vaccination rates. The authors provide discussion of the background, landscape, and stakeholder interests and the pros and cons of two voluntary policy options to increase vaccination. The policy options include: (a) financial incentives for providers and (b) an education emphasis for providers and staff. The authors conclude that based on considerations of cost, provider preference, and practicality of implementation, a continuing educational intervention is the preferred policy venue to increase vaccination rates. © 2014 Wiley Periodicals, Inc.
Full Text Available BACKGROUND: Because they can generate comparable predictions, mathematical models are ideal tools for evaluating alternative drug or vaccine allocation strategies. To remain credible, however, results must be consistent. Authors of a recent assessment of possible influenza vaccination strategies conclude that older children, adolescents, and young adults are the optimal targets, no matter the objective, and argue for vaccinating them. Authors of two earlier studies concluded, respectively, that optimal targets depend on objectives and cautioned against changing policy. Which should we believe? METHODS AND FINDINGS: In matrices whose elements are contacts between persons by age, the main diagonal always predominates, reflecting contacts between contemporaries. Indirect effects (e.g., impacts of vaccinating one group on morbidity or mortality in others result from off-diagonal elements. Mixing matrices based on periods in proximity with others have greater sub- and super-diagonals, reflecting contacts between parents and children, and other off-diagonal elements (reflecting, e.g., age-independent contacts among co-workers, than those based on face-to-face conversations. To assess the impact of targeted vaccination, we used a time-usage study's mixing matrix and allowed vaccine efficacy to vary with age. And we derived mortality rates either by dividing observed deaths attributed to pneumonia and influenza by average annual cases from a demographically-realistic SEIRS model or by multiplying those rates by ratios of (versus adding to them differences between pandemic and pre-pandemic mortalities. CONCLUSIONS: In our simulations, vaccinating older children, adolescents, and young adults averts the most cases, but vaccinating either younger children and older adults or young adults averts the most deaths, depending on the age distribution of mortality. These results are consistent with those of the earlier studies.
Full Text Available Pityriasis rosea is a common erythematosquamous eruption, typically presenting along the cleavage lines of the skin. A wide spectrum of atypical manifestations may challenge even the most experienced physician. Here we report a rare case of a suberythrodermic pityriasis rosea with gigantic plaques after an influenza vaccination, and we discuss the possible triggers of atypical manifestations of such a common dermatological disease in the setting of an altered immunity.
Lv, Min; Fang, Renfei; Wu, Jiang; Pang, Xinghuo; Deng, Ying; Lei, Trudy; Xie, Zheng
In order to improve influenza vaccination coverage, the coverage rate and reasons for non-vaccination need to be determined. In 2007, the Beijing Government published a policy providing free influenza vaccinations to elderly people living in Beijing who are older than 60. This study examines the vaccination coverage after the policy was carried out and factors influencing vaccination among the elderly in Beijing. A cross-sectional survey was conducted through the use of questionnaires in 2013. A total of 1673 eligible participants were selected by multistage stratified random sampling in Beijing using anonymous questionnaires in-person. They were surveyed to determine vaccination status and social demographic information. The influenza vaccination coverage was 38.7% among elderly people in Beijing in 2012. The most common reason for not being vaccinated was people thinking they did not need to have a flu shot. After controlling for age, gender, income, self-reported health status, and the acceptance of health promotion, the rate in rural areas was 2.566 (95% confidence interval [CI], 1.801-3.655, Pvaccination uptake. Those whom received information through television, community boards, or doctors were more likely to get vaccinated compared to those who did not (Odds Ratio [OR]=1.403, Pvaccine coverage in Beijing is much lower than that of developed countries with similar policies. The rural-urban disparity in coverage rate (64.1% versus 33.5%), may be explained by differing health provision systems and personal attitudes toward free services due to socioeconomic factors. Methods for increasing vaccination levels include increasing the focus on primary care and health education programs, particularly recommendations from doctors, to the distinct target populations, especially with a focus on expanding these efforts in urban areas. Copyright © 2016 Elsevier Ltd. All rights reserved.
Ayora-Talavera, Guadalupe; Flores, Gerardo Montalvo-Zurbia; Gómez-Carballo, Jesus; González-Losa, Refugio; Conde-Ferraez, Laura; Puerto-Solís, Marylin; López-Martínez, Irma; Díaz-Quiñonez, Alberto; Barrera-Badillo, Gisela; Acuna-Soto, Rodolfo; Livinski, Alicia A; Alonso, Wladimir J
While vaccination may be relatively straightforward for regions with a well-defined winter season, the situation is quite different for tropical regions. Influenza activity in tropical regions might be out of phase with the dynamics predicted for their hemispheric group thereby impacting the effectiveness of the immunization campaign. To investigate how the climatic diversity of Mexico hinders its existing influenza immunization strategy and to suggest that the hemispheric vaccine recommendations be tailored to the regional level in order to optimize vaccine effectiveness. We studied the seasonality of influenza throughoutMexico by modeling virological and mortality data.De-trended time series of each Mexican state were analyzed by Fourier decomposition to describe the amplitude and timing of annual influenza epidemic cycles and to compare with each the timing of the WHO's Northern and Southern Hemispheric vaccination schedule. The timings of the primary (major) peaks of both virological and mortality data for most Mexican states are well aligned with the Northern Hemisphere winter (December-February) and vaccine schedule. However, influenza peaks in September in the three states of the Yucatan Peninsula. Influenza-related mortality also peaks in September in Quintana Roo and Yucatan whereas it peaks in May in Campeche. As the current timing of vaccination in Mexico is between October and November, more than half of the annual influenza cases have already occurred in the Yucatan Peninsula states by the time the Northern Hemispheric vaccine is delivered and administered. The current Northern Hemispheric influenza calendar adopted for Mexico is not optimal for the Yucatan Peninsula states thereby likely reducing the effectiveness of the immunization of the population. We recommend that Mexico tailor its immunization strategy to better reflect its climatologic and epidemiological diversity and adopt the WHO Southern Hemisphere influenza vaccine and schedule for the
Emborg, Hanne Dorthe; Krause, Tyra Grove; Nielsen, Lene
In Denmark, both influenza A(H1N1)pdm09 and influenza B co-circulated in the 2015/16 season. We estimated the vaccine effectiveness (VE) of the trivalent influenza vaccine in patients 65 years and older using the test-negative case-control design. The adjusted VE against influenza A(H1N1)pdm09 wa...
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 att...
Bödeker, Birte; Betsch, Cornelia; Wichmann, Ole
Pregnant women and their newborns have an increased risk of developing severe influenza and influenza-related complications. In Germany, seasonal influenza vaccination is recommended for pregnant women since 2010. However, little is known about pregnant women's vaccination-related knowledge and attitudes, as well as their risk perceptions. This study therefore assessed pregnant women's vaccination-related knowledge, risk perceptions related to influenza disease and influenza vaccination during pregnancy, and aimed to identify determinants of influenza vaccination uptake during pregnancy in Germany. Between 2012 and 2014, a nationwide web-based prospective cohort study with follow-up interviews was conducted in initially pregnant women who gave birth over the study period. Control groups were set up in a cross-sectional fashion during the follow-up interviews. Women who participated in both, the baseline interview before giving birth and in the 1st interview after giving birth were included in the analysis. Univariate and multiple logistic regression were used to identify associations between influenza vaccination uptake and sociodemographic characteristics as well as items assessing attitude and knowledge. In total, 838 women were included in the analyses. Pregnant women had a positive attitude towards vaccination in general, but only modest vaccination knowledge. Overall, 10.9 % of women were vaccinated against seasonal influenza during pregnancy. While pregnant women perceived classical childhood diseases to be more risky than the respective vaccinations, this relation reversed for influenza: The risk of vaccination was perceived higher than the risk of the disease. These two types of risk perceptions independently determined influenza vaccination uptake-higher perception of disease risk and lower perceptions of vaccination-related risks increased uptake. Additionally, knowledge about the vaccination recommendation for pregnant women and a positive gynaecologist
Jang, Yo Han; Kim, Joo Young; Byun, Young Ho; Son, Ahyun; Lee, Jeong-Yoon; Lee, Yoon Jae; Chang, Jun; Seong, Baik Lin
Influenza virus infections continually pose a major public health threat with seasonal epidemics and sporadic pandemics worldwide. While currently licensed influenza vaccines provide only strain-specific protection, antigenic drift and shift occasionally render the viruses resistant to the host immune responses, which highlight the need for a vaccine that provides broad protection against multiple subtypes. In this study, we suggest a vaccination strategy using cold-adapted, live attenuated influenza vaccines (CAIVs) to provide a broad, potent, and safe cross-protection covering antigenically distinct hemagglutinin (HA) groups 1 and 2 influenza viruses. Using a mouse model, we tested different prime-boost combinations of CAIVs for their ability to induce humoral and T-cell responses, and protective efficacy against H1 and H5 (HA group 1) as well as H3 and H7 (HA group 2) influenza viruses. Notably, even in the absence of antibody-mediated neutralizing activity or HA inhibitory activity in vitro , CAIVs provided a potent protection against heterologous and heterosubtypic lethal challenges in vivo . Heterologous combination of prime (H1)-boost (H5) vaccine strains showed the most potent cross-protection efficacy. In vivo depletion experiments demonstrated not only that T cells and natural killer cells contributed to the cross-protection, but also the involvement of antibody-dependent mechanisms for the cross-protection. Vaccination-induced antibodies did not enhance the infectivity of heterologous viruses, and prime vaccination did not interfere with neutralizing antibody generation by the boost vaccination, allaying vaccine safety concerns associated with heterogeneity between the vaccines and challenge strains. Our data show that CAIV-based strategy can serve as a simple but powerful option for developing a "truly" universal influenza vaccine providing pan-influenza A protection, which has not been achieved yet by other vaccine strategies. The promising results
Jang, Yo Han; Kim, Joo Young; Byun, Young Ho; Son, Ahyun; Lee, Jeong-Yoon; Lee, Yoon Jae; Chang, Jun; Seong, Baik Lin
Influenza virus infections continually pose a major public health threat with seasonal epidemics and sporadic pandemics worldwide. While currently licensed influenza vaccines provide only strain-specific protection, antigenic drift and shift occasionally render the viruses resistant to the host immune responses, which highlight the need for a vaccine that provides broad protection against multiple subtypes. In this study, we suggest a vaccination strategy using cold-adapted, live attenuated influenza vaccines (CAIVs) to provide a broad, potent, and safe cross-protection covering antigenically distinct hemagglutinin (HA) groups 1 and 2 influenza viruses. Using a mouse model, we tested different prime–boost combinations of CAIVs for their ability to induce humoral and T-cell responses, and protective efficacy against H1 and H5 (HA group 1) as well as H3 and H7 (HA group 2) influenza viruses. Notably, even in the absence of antibody-mediated neutralizing activity or HA inhibitory activity in vitro, CAIVs provided a potent protection against heterologous and heterosubtypic lethal challenges in vivo. Heterologous combination of prime (H1)–boost (H5) vaccine strains showed the most potent cross-protection efficacy. In vivo depletion experiments demonstrated not only that T cells and natural killer cells contributed to the cross-protection, but also the involvement of antibody-dependent mechanisms for the cross-protection. Vaccination-induced antibodies did not enhance the infectivity of heterologous viruses, and prime vaccination did not interfere with neutralizing antibody generation by the boost vaccination, allaying vaccine safety concerns associated with heterogeneity between the vaccines and challenge strains. Our data show that CAIV-based strategy can serve as a simple but powerful option for developing a “truly” universal influenza vaccine providing pan-influenza A protection, which has not been achieved yet by other vaccine strategies. The promising
Longini, Ira M; Halloran, M Elizabeth
Despite evidence that vaccinating schoolchildren against influenza is effective in limiting community-level transmission, the United States has had a long-standing government strategy of recommending that vaccine be concentrated primarily in high-risk groups and distributed to those people who keep the health system and social infrastructure operating. Because of this year's influenza vaccine shortage, a plan was enacted to distribute the limited vaccine stock to these groups first. This vaccination strategy, based on direct protection of those most at risk, has not been very effective in reducing influenza morbidity and mortality. Although it is too late to make changes this year, the current influenza vaccine crisis affords the opportunity to examine an alternative for future years. The alternative plan, supported by mathematical models and influenza field studies, would be to concentrate vaccine in schoolchildren, the population group most responsible for transmission, while also covering the reachable high-risk groups, who would also receive considerable indirect protection. In conjunction with a plan to ensure an adequate vaccine supply, this alternative influenza vaccination strategy would help control interpandemic influenza and be instrumental in preparing for pandemic influenza. The effectiveness of the alternative plan could be assessed through nationwide community studies.
Diana C Otczyk
Full Text Available Pneumonia in childhood is endemic in large parts of the world and in particular, in developing countries, as well as in many indigenous communities within developed nations. Haemophilus influenzae type b and Streptococcus pneumoniae conjugate vaccines are currently available against the leading bacterial causes of pneumonia. The use of the vaccines in both industrialised and developing countries have shown a dramatic reduction in the burden of pneumonia and invasive disease in children. However, the greatest threat facing pneumococcal conjugate vaccine effectiveness is serotype replacement. The current vaccines provide serotype-specific, antibody–mediated protection against only a few of the 90+ capsule serotypes. Therefore, there has been a focus in recent years to rapidly advance technologies that will result in broader disease coverage and more affordable vaccines that can be used in developing countries. The next generation of pneumococcal vaccines have advanced to clinical trials.
Kim, Hanna; Lindley, Megan C; Dube, Donna; Kalayil, Elizabeth J; Paiva, Kristi A; Raymond, Patricia
In October 2012, the Rhode Island Department of Health (HEALTH) amended its health care worker (HCW) vaccination regulations to require all HCWs to receive annual influenza vaccination or wear a surgical mask during direct patient contact when influenza is widespread. Unvaccinated HCWs failing to wear a mask are subject to a fine and disciplinary action. To describe the implementation of the 2012 Rhode Island HCW influenza vaccination regulations and examine their impact on vaccination coverage. Two data sources were used: (1) a survey of all health care facilities subject to the HCW regulations and (2) HCW influenza vaccination coverage data reported to HEALTH by health care facilities. Descriptive statistics and paired t tests were performed using SAS Release 9.2. For the 2012-2013 influenza season, 271 inpatient and outpatient health care facilities in Rhode Island were subject to the HCW regulations. Increase in HCW influenza vaccination coverage. Of the 271 facilities, 117 facilities completed the survey (43.2%) and 160 facilities reported vaccination data to HEALTH (59.0%). Between the 2011-2012 and 2012-2013 influenza seasons, the proportion of facilities having a masking policy, as required by the revised regulations, increased from 9.4% to 94.0% (P employee HCWs in Rhode Island increased from 69.7% in the 2011-2012 influenza season to 87.2% in the 2012-2013 season. Rhode Island's experience demonstrates that statewide HCW influenza vaccination requirements incorporating mask wearing and moderate penalties for noncompliance can be effective in improving influenza vaccination coverage among HCWs.
Full Text Available Rheumatoid arthritis (RA is the most common chronic inflammatory joint disease. Multiple scientific articles have documented that vaccinations for influenza, MMR, and HBV, to name a few, could be triggers of RA in genetically predisposed individuals. However, there is limited data regarding the association of swine flu vaccine (H1N1 and RA. We report the case of a Mexican American female who developed RA right after vaccination with H1N1 vaccine. Genetically, RA has consistently been associated with an epitope in the third hypervariable region of the HLA-DR chains, known as the “shared epitope”, which is found primarily in DR4 and DR1 regions. The presence of HLA-DRB1 alleles is associated with susceptibility to RA in Mexican Americans. Hence, certain individuals with the presence of the “shared epitope” may develop RA following specific vaccinations. To our knowledge, this is the first reported case of RA following vaccination with the swine flu vaccine.
... palsy) that can lead to breathing or swallowing problems. Anyone with a weakened immune system. Anyone in close contact with someone whose immune system is so weak they require care in a protected.... In such cases, the only revision to the influenza VIS is the notation of the flu season for which the...
Roberts Paul C
Full Text Available Abstract 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.
... models to generate quantitative estimates of the benefits and risks of influenza vaccination. The public...] Use of Influenza Disease Models To Quantitatively Evaluate the Benefits and Risks of Vaccines: A... Influenza Disease Models to Quantitatively Evaluate the Benefits and Risks of Vaccines: A Technical Workshop...
William C Weldon
Full Text Available Recent studies have demonstrated the effectiveness of vaccine delivery to the skin by vaccine-coated microneedles; however there is little information on the effects of adjuvants using this approach for vaccination. Here we investigate the use of TLR ligands as adjuvants with skin-based delivery of influenza subunit vaccine. BALB/c mice received 1 µg of monovalent H1N1 subunit vaccine alone or with 1 µg of imiquimod or poly(I:C individually or in combination via coated microneedle patches inserted into the skin. Poly(I:C adjuvanted subunit influenza vaccine induced similar antigen-specific immune responses compared to vaccine alone when delivered to the skin by microneedles. However, imiquimod-adjuvanted vaccine elicited higher levels of serum IgG2a antibodies and increased hemagglutination inhibition titers compared to vaccine alone, suggesting enhanced induction of functional antibodies. In addition, imiquimod-adjuvanted vaccine induced a robust IFN-γ cellular response. These responses correlated with improved protection compared to influenza subunit vaccine alone, as well as reduced viral replication and production of pro-inflammatory cytokines in the lungs. The finding that microneedle delivery of imiquimod with influenza subunit vaccine induces improved immune responses compared to vaccine alone supports the use of TLR7 ligands as adjuvants for skin-based influenza vaccines.
Corace, Kimberly; Prematunge, Chatura; McCarthy, Anne; Nair, Rama C; Roth, Virginia; Hayes, Thomas; Suh, Kathryn N; Balfour, Louise; Garber, Gary
Health care worker (HCW) vaccination was critical to protecting HCW during the H1N1 pandemic. However, vaccine uptake rates fell below recommended targets. This study examined motivators and barriers influencing HCW pH1N1 vaccination to identify modifiable factors that can improve influenza vaccine uptake. A cross-sectional survey was conducted at a large Canadian tertiary care hospital. HCW (N = 3,275) completed measures of demographics, vaccination history, influenza risk factors, and attitudes toward pH1N1 vaccination. Self-reported vaccination was verified with staff vaccination records. Of the total sample, 2,862 (87.4%) HCW received the pH1N1 vaccine. Multiple logistic regression analyses were used to predict HCW vaccination. HCW attitudes toward vaccination significantly predicted vaccination, even after adjusting for demographics, vaccine history, and influenza risk factors. This model correctly predicted 95% (confidence interval [CI]: 0.93-0.96) of HCW vaccination. Key modifiable factors driving HCW vaccination include (1) desire to protect family members and patients, (2) belief that vaccination is important even if one is healthy, (3) confidence in vaccine safety, and (4) supervisor and physician encouragement. This research identified fundamental reasons why HCW get vaccinated and provides direction for future influenza vaccination programs. To enhance vaccine uptake, it is important to target HCW attitudes in influenza vaccine campaigns and create a culture of vaccine promotion in the workplace, including strong messaging from supervisors and physicians. Copyright © 2013 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.
B. Baras (Benoît); K.J. Stittelaar (Koert); J.H. Simon (James); R.J.M.M. Thoolen (Robert); S.P. Mossman (Sally); F.H. Pistoor (Frank); G. van Amerongen (Geert); M.A. Wettendorff (Martine); E. Hanon (Emmanuel); A.D.M.E. Osterhaus (Albert)
textabstractBackground. Unprecedented spread between birds and mammals of highly pathogenic avian influenza viruses (HPAI) of the H5N1 subtype has resulted in hundreds of human infections with a high fatality rate. This has highlighted the urgent need for the development of H5N1 vaccines that can be
Kristensen, Anne B; Lay, William N; Ana-Sosa-Batiz, Fernanda
to immunize this at-risk group. IMPORTANCE: Infection with HIV is associated with increasing disease severity following influenza infections, and annual influenza vaccinations are recommended for this target group. However, HIV-infected individuals respond relatively poorly to vaccination compared to healthy......This study seeks to assess the ability of seasonal trivalent inactivated influenza vaccine (TIV) to induce nonneutralizing antibodies (Abs) with Fc-mediated functions in HIV-uninfected and HIV-infected subjects. Functional influenza-specific Ab responses were studied in 30 HIV-negative and 27 HIV......-positive subjects immunized against seasonal influenza. All 57 subjects received the 2015 TIV. Fc-mediated antihemagglutinin (anti-HA) Ab activity was measured in plasma before and 4 weeks after vaccination using Fc-receptor-binding assays, NK cell activation assays, and phagocytosis assays. At baseline, the HIV...
At this time every year, the Medical Service suggests that you should get vaccinated against seasonal flu. We would like to remind you that vaccination is the best method of protecting yourself and others against this contagious illness which can have serious consequences for certain people, especially those suffering from chronic medical conditions (e.g. chronic pulmonary, cardiovascular or kidney disease or diabetes), pregnant women, people suffering from obesity (BMI>30) and those over 65. As the Medical Service does not supply the vaccine, you must purchase it from a pharmacy (without the need for a prescription in France). From the beginning of October you can then bring your vaccine to the Infirmary (Building 57-Ground floor) and get vaccinated without an appointment between 9 a.m. - 12 p.m. and 2 p.m. - 4:30 p.m. For the purposes of health insurance reimbursement, you can get a prescription from the Medical Service either on the day of the injection or beforehand. Reminder: The...
At this time every year the Medical Service suggests that you should get vaccinated against seasonal flu. We would like to remind you that vaccination is the best method of protecting yourself and others against this contagious illness which can have serious consequences for certain people, especially those suffering from chronic medical conditions (e.g. chronic pulmonary, cardiovascular or kidney disease or diabetes), pregnant women, people suffering from obesity (BMI>30) and those over 65. As the Medical Service does not supply the vaccine, you must purchase it from a pharmacy (in France you don't need a prescription). From the beginning of October you can then bring your vaccine to the Infirmary (Building 57-Ground floor) and get vaccinated without an appointment between 9 a.m. and 12 a.m. and 2 p.m. to 4:30 p.m. For the purposes of health insurance reimbursement, you can get a prescription from the Medical Service either on the day of the injection or beforehand. Reminder:...
At this time every year the Medical Service suggests that you should get vaccinated against seasonal flu. We would like to remind you that vaccination is the best method of protecting yourself and others against this contagious illness which can have serious consequences for certain people, especially those suffering from chronic medical conditions (e.g. chronic pulmonary, cardiovascular or kidney disease or diabetes), pregnant women, people suffering from obesity (BMI>30) and those over 65. As the Medical Service does not supply the vaccine, you must purchase it from a pharmacy (in France without the need for a prescription). From the beginning of October you can then bring your vaccine to the Infirmary (Building 57-Ground floor) and get vaccinated without an appointment between 9 a.m. and 12 a.m. and 2 p.m. to 4:30 p.m. For the purposes of health insurance reimbursement, you can get a prescription from the Medical Service either on the day of the injection or beforehand. Reminder: The Medical Se...
de Boer, Pieter; Pitman, R.J.; Macabeo, B.; Chit, A.; Postma, M.J.; Crépey, P.
BACKGROUND: Currently used trivalent influenza vaccines (TIVs) contain two strains of influenza A and one strain of influenza B. However, co-circulation of two distinct B lineages and difficulties in predicting which lineage will predominate in the next season have led to frequent B-strain
Shono, Aiko; Kondo, Masahide
Seasonal influenza vaccine was once part of the routine immunization schedule that is routinely offered to all children in Japan, but it is now excluded from the schedule. This study aimed to investigate factors influential to parents' decision to have their children receive seasonal influenza vaccine, as well as types of seasonal influenza vaccine information that is given to parents. We conducted a cross-sectional online survey of 555 participants who have at least one child younger than 13 years of age. Respondents were asked to categorize the history of influenza vaccination of their youngest child as either 'annual' , 'sometimes' , or 'never'. Participants were also asked about potentially influential factors in their decision to have their children receive a seasonal influenza vaccine. A total of 75% of respondents answered that their youngest child had received a seasonal influenza vaccine, and 57% of respondents answered that their child receives the vaccine every year. The higher income group was more likely than the lowest income group to have a history of influenza vaccine uptake. A recommendation from a pediatrician or school/nursery to have their child vaccinated was also positively associated with a history of influenza vaccine uptake. The most common reason for a pediatrician's recommendation was 'it leads to milder symptoms if infected'. The main finding of the study is a significant association between household income and influenza vaccination of the youngest child in the household. We also found that cost could be a barrier to vaccinating children in low income households and that information from pediatricians and schools/nurseries could motivate parents to have their children vaccinated.
Oshansky, Christine M; Wong, Sook-San; Jeevan, Trushar; Smallwood, Heather S; Webby, Richard J; Shafir, Shira C; Thomas, Paul G
provided greater specificity for the detection of zoonotic infection. However, influenza vaccination appears to promote cross-reactive antibodies and may provide enhanced protection to novel influenza viruses. Annual vaccinations are necessary to ameliorate influenza disease due to drifted viral variants that emerge in the population. Major shifts in the antigenicity of influenza viruses can result in immunologically distinct viruses that can cause more severe disease in humans. Historically, genetic reassortment between avian, swine, or human influenza viruses has caused influenza pandemics in humans several times in the last century. Therefore, it is important to design vaccines to elicit broad protective responses to influenza infections. Because avian influenza viruses have an important role in emerging infections, we tested whether occupational exposure to birds can elicit immune responses to avian influenza viruses in humans. Instead of a specific occupational exposure, the strongest association of enhanced cross-reactive antibody responses was receipt of seasonal influenza vaccination. Therefore, individuals with preexisting immune responses to seasonal human influenza viruses have substantial cross-reactive antibody and T cell responses that may lead to enhanced protection to novel influenza viruses. Copyright © 2014 Oshansky et al.
Full Text Available Abstract Background Previous studies have shown influenza vaccine uptake in UK nursing home residents to be low. Very little information exists regarding the uptake of pneumococcal vaccine in this population. The formulation of policies relating to the vaccination of residents has been proposed as a simple step that may help improve vaccine uptake in care homes. Methods A postal questionnaire was sent to matrons of all care homes with nursing within the Greater Nottingham area in January 2006. Non respondents were followed up with up to 3 phone calls. Results 30% (16/53 of respondents reported having a policy addressing influenza vaccination and 15% (8/53 had a policy addressing pneumococcal vaccination. Seasonal influenza vaccine coverage in care homes with a vaccination policy was 87% compared with 84% in care homes without a policy (p = 0.47. The uptake of pneumococcal vaccination was found to be low, particularly in care homes with no vaccination policy. Coverage was 60% and 32% in care homes with and without a vaccination policy respectively (p = 0.06. This result was found to be statistically significant on multivariate analysis (p = 0.03, R = 0.46 Conclusion The uptake of influenza vaccine among care home residents in the Nottingham region is relatively high, although pneumococcal vaccine uptake is low. This study shows that there is an association between pneumococcal vaccine uptake and the existence of a vaccination policy in care homes, and highlights that few care homes have vaccination policies in place.
Poland, Gregory A
Individual and national/cultural differences were apparent in response to the 2009-2010 influenza pandemic. Overall pandemic influenza immunization rates were low across all nations, including among healthcare workers. Among the reasons for the low coverage rates may have been a lack of concern about the individual risk of influenza, which may translate into a lack of willingness or urgency to be vaccinated, particularly if there is mistrust of information provided by public health or governmental authorities. Intuitively, a link between willingness to be vaccinated against seasonal influenza and against pandemic influenza exists, given the similarities in decision-making for this infection. As such, the public is likely to share common concerns regarding pandemic and seasonal influenza vaccination, particularly in the areas of vaccine safety and side effects, and personal risk. Given the public's perception of the low level of virulence of the recent pandemic influenza virus, there is concern that the perception of a lack of personal risk of infection and risk of vaccine side effects could adversely affect seasonal vaccine uptake. While governments are more often concerned about public anxiety and panic, as well as absenteeism of healthcare and other essential workers during a pandemic, convincing the public of the threat posed by pandemic or seasonal influenza is often the more difficult, and underappreciated task. Thus, appropriate, timely, and data-driven health information are very important issues in increasing influenza vaccine coverage, perhaps even more so in western societies where trust in government and public health reports may be lower than in other countries. This article explores what has been learned about cross-cultural responses to pandemic influenza, and seeks to apply those lessons to seasonal influenza immunization programs. 2010 Elsevier Ltd. All rights reserved.
Shibata, Natsumi; Kimura, Shinya; Hoshino, Takahiro; Takeuchi, Masato; Urushihara, Hisashi
To date, few large-scale comparative effectiveness studies of influenza vaccination have been conducted in Japan, since marketing authorization for influenza vaccines in Japan has been granted based only on the results of seroconversion and safety in small-sized populations in clinical trial phases not on the vaccine effectiveness. We evaluated the clinical effectiveness of influenza vaccination for children aged 1-15 years in Japan throughout four influenza seasons from 2010 to 2014 in the real world setting. We conducted a cohort study using a large-scale claims database for employee health care insurance plans covering more than 3 million people, including enrollees and their dependents. Vaccination status was identified using plan records for the influenza vaccination subsidies. The effectiveness of influenza vaccination in preventing influenza and its complications was evaluated. To control confounding related to influenza vaccination, odds ratios (OR) were calculated by applying a doubly robust method using the propensity score for vaccination. Total study population throughout the four consecutive influenza seasons was over 116,000. Vaccination rate was higher in younger children and in the recent influenza seasons. Throughout the four seasons, the estimated ORs for influenza onset were statistically significant and ranged from 0.797 to 0.894 after doubly robust adjustment. On age stratification, significant ORs were observed in younger children. Additionally, ORs for influenza complication outcomes, such as pneumonia, hospitalization with influenza and respiratory tract diseases, were significantly reduced, except for hospitalization with influenza in the 2010/2011 and 2012/2013 seasons. We confirmed the clinical effectiveness of influenza vaccination in children aged 1-15 years from the 2010/2011 to 2013/2014 influenza seasons. Influenza vaccine significantly prevented the onset of influenza and was effective in reducing its secondary complications
Hirve, S.; Lambach, P.; Paget, J.; Vandemaele, K.; Fitzner, J.; Zhang, W.
Aim: The evidence needed for tropical countries to take informed decisions on influenza vaccination is scarce. This paper reviews policy, availability, use and effectiveness of seasonal influenza vaccine in tropical and subtropical countries. Method: Global health databases were searched in three
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…
Mylius, S.D.; Hagenaars, T.H.J.; Lugner, A.K.; Wallinga, J.
The limited production capacity for vaccines raises the question what the best strategy is for allocating the vaccine to mitigate an influenza pandemic. We developed an age-structured model for spread of an influenza pandemic and validated it against observations from the Asian flu pandemic. Two
Hirve, S.; Lambach, P.; Paget, J.; Vandemaele, K.; Fitzner, J.; Zhang, W.
AIM: The evidence needed for tropical countries to take informed decisions on influenza vaccination is scarce. This article reviews policy, availability, use and effectiveness of seasonal influenza vaccine in tropical and subtropical countries. METHOD: Global health databases were searched in three
Dauner, Allison; Agrawal, Pankaj; Salvatico, Jose; Tapia, Tenekua; Dhir, Vipra; Shaik, S Farzana; Drake, Donald R; Byers, Anthony M
Increasing research and development costs coupled with growing concerns over healthcare expenditures necessitate the generation of pre-clinical testing models better able to predict the efficacy of vaccines, drugs and biologics. An ideal system for evaluating vaccine immunogenicity will not only be reliable but also physiologically relevant, able to be influenced by immunomodulatory characteristics such as age or previous exposure to pathogens. We have previously described a fully autologous human cell-based MIMIC® (Modular IMmune In vitro Construct) platform which enables the evaluation of innate and adaptive immunity in vitro, including naïve and recall responses. Here, we establish the ability of this module to display reduced antibody production and T cell activation upon in vitro influenza vaccination of cells from elderly adults. In the MIMIC® system, we observe a 2.7-4.2-fold reduction in strain-specific IgG production to seasonal trivalent influenza vaccine (TIV) in the elderly when compared to adults, as well as an age-dependent decline in the generation of functional antibodies. A parallel decline in IgG production with increasing age was detected via short-term ex vivo stimulation of B cells after in vivo TIV vaccination in the same cohort. Using MIMIC®, we also detect a reduction in the number but not proportion of TIV-specific multifunctional CD154 + IFNγ + IL-2 + TNFα + CD4 + T cells in elderly adults. Inefficient induction of multifunctional helper T cells with TIV stimulation in MIMIC® despite a normalized number of initial CD4 + T cells suggests a possible mechanism for an impaired anti-TIV IgG response in elderly adults. The ability of the MIMIC® system to recapitulate differential age-associated responses in vitro provides a dynamic platform for the testing of vaccine candidates and vaccine enhancement strategies in a fully human model including the ability to interrogate specific populations, such as elderly adults. Copyright © 2017
... Prevent Flu Good Health Habits Cover Your Cough Home, Work & School Prevention Vaccine Benefits Symptoms & Diagnosis Flu Symptoms & ... result was 9.7% to 36.5%. A separate study published in The Lancet ... 38,000 residents of 823 nursing homes in 38 states during the 2013-14 flu ...
Schlaudecker, Elizabeth P; Steinhoff, Mark C; Omer, Saad B; McNeal, Monica M; Roy, Eliza; Arifeen, Shams E; Dodd, Caitlin N; Raqib, Rubhana; Breiman, Robert F; Zaman, K
Antenatal immunization of mothers with influenza vaccine increases serum antibodies and reduces the rates of influenza illness in mothers and their infants. We report the effect of antenatal immunization on the levels of specific anti-influenza IgA levels in human breast milk. (ClinicalTrials.gov identifier NCT00142389; http://clinicaltrials.gov/ct2/show/NCT00142389). The Mother's Gift study was a prospective, blinded, randomized controlled trial that assigned 340 pregnant Bangladeshi mothers to receive either trivalent inactivated influenza vaccine, or 23-valent pneumococcal polysaccharide vaccine during the third trimester. We evaluated breast milk at birth, 6 weeks, 6 months, and 12 months, and serum at 10 weeks and 12 months. Milk and serum specimens from 57 subjects were assayed for specific IgA antibody to influenza A/New Caledonia (H1N1) using an enzyme-linked immunosorbent assay (ELISA) and a virus neutralization assay, and for total IgA using ELISA. Influenza-specific IgA levels in breast milk were significantly higher in influenza vaccinees than in pneumococcal controls for at least 6 months postpartum (p = 0.04). Geometric mean concentrations ranged from 8.0 to 91.1 ELISA units/ml in vaccinees, versus 2.3 to 13.7 ELISA units/mL in controls. Virus neutralization titers in milk were 1.2 to 3 fold greater in vaccinees, and correlated with influenza-specific IgA levels (r = 0.86). Greater exclusivity of breastfeeding in the first 6 months of life significantly decreased the expected number of respiratory illness with fever episodes in infants of influenza-vaccinated mothers (p = 0.0042) but not in infants of pneumococcal-vaccinated mothers (p = 0.4154). The sustained high levels of actively produced anti-influenza IgA in breast milk and the decreased infant episodes of respiratory illness with fever suggest that breastfeeding may provide local mucosal protection for the infant for at least 6 months. Studies are needed to determine the
Rousseau, Louise; Guay, Maryse; Archambault, Denis; El m'ala, Zahra; Abdelaziz, Nadia
Despite the implementation of a Quebec immunization program against influenza and pneumococcal disease (PQIIP), vaccine coverage has remained low. There have been many studies on personal barriers to vaccination, but few have explored other kinds of barriers. To explore the presence of barriers in relation to the organization of the health care system and to propose recommendations for increasing vaccine coverage. Within a mixed protocol, a phone survey of 996 people in the target population and a case study implicating the follow-up of the PQIIP with all the site and actor categories via 43 semistructured interviews and 4 focus groups were realized. Survey data underwent a descriptive statistical analysis. Qualitative analysis followed the Miles and Huberman approach. The results indicate the presence of barriers with regard to information accessibility. These include access to: the physicians' recommendation, knowledge of the efficacy or the security of vaccines, and admissibility of clients to the PQIIP. Organizational barriers were also found to limit access to vaccination, especially in terms of restricted choices of time and location. Coordination and incentives mechanisms are not optimal. Removal of organizational barriers depends more on strategic rather than structural factors. Addressing organizational barriers should be an important component of strategies aimed at improving vaccine coverage. Public health authorities should focus on strategic management of the information and inter-organizational environment.
Full Text Available Equine influenza (EI outbreaks occurred on 19 premises in Ireland during 2014. Disease affected thoroughbred (TB and non-TB horses/ponies on a variety of premises including four racing yards. Initial clinical signs presented on 16 premises within a two-month period. Extensive field investigations were undertaken, and the diagnostic effectiveness of a TaqMan RT-PCR assay was demonstrated in regularly-vaccinated and sub-clinically-affected horses. Epidemiological data and repeat clinical samples were collected from 305 horses, of which 40% were reported as clinically affected, 39% were identified as confirmed cases and 11% were sub-clinically affected. Multivariable analysis demonstrated a significant association between clinical signs and age, vaccination status and number of vaccine doses received. Vaccine breakdown was identified in 31% of horses with up to date vaccination records. This included 27 horses in four different racing yards. Genetic and antigenic analysis identified causal viruses as belonging to Clade 2 of the Florida sublineage (FCL2. At the time of this study, no commercially available EI vaccine in Ireland had been updated in line with World Organisation for Animal Health (OIE recommendations to include a FCL2 virus. The findings of this study highlight the potential ease with which EI can spread among partially immune equine populations.
Petrie, Joshua G; Gordon, Aubree
The National Institute of Allergy and Infectious Diseases recently published a strategic plan for the development of a universal influenza vaccine. This plan focuses on improving understanding of influenza infection, the development of influenza immunity, and rational design of new vaccines. Epidemiological studies such as prospective, longitudinal cohort studies are essential to the completion of these objectives. In this review, we discuss the contributions of epidemiological studies to our current knowledge of vaccines and correlates of immunity, and how they can contribute to the development and evaluation of the next generation of influenza vaccines. These studies have been critical in monitoring the effectiveness of current influenza vaccines, identifying issues such as low vaccine effectiveness, reduced effectiveness among those who receive repeated vaccination, and issues related to egg adaptation during the manufacturing process. Epidemiological studies have also identified population-level correlates of protection that can inform the design and development of next generation influenza vaccines. Going forward, there is an enduring need for epidemiological studies to continue advancing knowledge of correlates of protection and the development of immunity, to evaluate and monitor the effectiveness of next generation influenza vaccines, and to inform recommendations for their use.
Torner, Núria; Martínez, Ana; Basile, Luca; Marcos, M Angeles; Antón, Andrés; Mar Mosquera, M; Isanta, Ricard; Cabezas, Carmen; Jané, Mireia; Domínguez, Angela; Program of Catalonia, the PIDIRAC Sentinel Surveillance
Influenza vaccination aims at reducing the incidence of serious disease, complications and death among those with the most risk of severe influenza disease. Influenza vaccine effectiveness (VE) through sentinel surveillance data from the PIDIRAC program (Daily Acute Respiratory Infection Surveillance of Catalonia) during 2010–2011, 2011–2012, and 2012–2013 influenza seasons, with three different predominant circulating influenza virus (IV) types [A(H1N1)pdm09, A(H3N2) and B, respectively] was assessed. The total number of sentinel samples with known vaccination background collected during the study period was 3173, 14.7% of which had received the corresponding seasonal influenza vaccine. 1117 samples (35.2%) were positive for IV. A retrospective negative case control design was used to assess vaccine effectiveness (VE) for the entire period and for each epidemic influenza season. An overall VE of 58.1% (95% CI:46.8–67) was obtained. Differences in VE according to epidemic season were observed, being highest for the 2012–2013 season with predominance of IV type B (69.7% ;95% CI:51.5–81) and for the 2010–2011 season, with predominance of the A(H1N1)pdm09 influenza virus strain (67.2% ;95%CI:49.5–78.8) and lowest for the 2011–2012 season with A(H3N2) subtype predominance (34.2% ;95%CI:4.5–54.6). Influenza vaccination prevents a substantial number of influenza-associated illnesses. Although vaccines with increased effectiveness are needed and the search for a universal vaccine that is not subject to genetic modifications might increase VE, nowadays only the efforts to increase vaccination rates of high-risk population and healthcare personnel let reduce the burden of influenza and its complications. PMID:25483540
Benne, CA; Harmsen, M; vanderGraaff, W; Verheul, AFM; Snippe, H; Kraaijeveld, CA
The influence of various adjuvants on the development of influenza virus neutralizing antibodies and distribution of anti-influenza virus IgG isotypes after immunization of mice with influenza A (H3N2) subunit vaccine was investigated. Serum titres of influenza virus neutralizing antibodies and
Nelson, Martha I; Schaefer, Rejane; Gava, Danielle; Cantão, Maurício Egídio; Ciacci-Zanella, Janice Reis
The evolutionary origins of the influenza A(H1N1)pdm09 virus that caused the first outbreak of the 2009 pandemic in Mexico remain unclear, highlighting the lack of swine surveillance in Latin American countries. Although Brazil has one of the largest swine populations in the world, influenza was not thought to be endemic in Brazil's swine until the major outbreaks of influenza A(H1N1)pdm09 in 2009. Through phylogenetic analysis of whole-genome sequences of influenza viruses of the H1N1, H1N2, and H3N2 subtypes collected in swine in Brazil during 2009-2012, we identified multiple previously uncharacterized influenza viruses of human seasonal H1N2 and H3N2 virus origin that have circulated undetected in swine for more than a decade. Viral diversity has further increased in Brazil through reassortment between co-circulating viruses, including A(H1N1)pdm09. The circulation of multiple divergent hemagglutinin lineages challenges the design of effective cross-protective vaccines and highlights the need for additional surveillance.
Schaefer, Rejane; Gava, Danielle; Cantão, Maurício Egídio; Ciacci-Zanella, Janice Reis
The evolutionary origins of the influenza A(H1N1)pdm09 virus that caused the first outbreak of the 2009 pandemic in Mexico remain unclear, highlighting the lack of swine surveillance in Latin American countries. Although Brazil has one of the largest swine populations in the world, influenza was not thought to be endemic in Brazil’s swine until the major outbreaks of influenza A(H1N1)pdm09 in 2009. Through phylogenetic analysis of whole-genome sequences of influenza viruses of the H1N1, H1N2, and H3N2 subtypes collected in swine in Brazil during 2009–2012, we identified multiple previously uncharacterized influenza viruses of human seasonal H1N2 and H3N2 virus origin that have circulated undetected in swine for more than a decade. Viral diversity has further increased in Brazil through reassortment between co-circulating viruses, including A(H1N1)pdm09. The circulation of multiple divergent hemagglutinin lineages challenges the design of effective cross-protective vaccines and highlights the need for additional surveillance. PMID:26196759
Full Text Available Persistent infection with high-risk human papillomavirus (HPV types, most often HPV16 and HPV18, causes all cervical and most anal cancers, and a subset of vulvar, vaginal, penile and oropharyngeal carcinomas. Two prophylactic virus-like particle (VLPs-based vaccines, are available that protect against vaccine type-associated persistent infection and associated disease, yet have no therapeutic effect on existing lesions or infections. We have generated recombinant live-attenuated influenza A viruses expressing the HPV16 oncogenes E6 and E7 as experimental immunotherapeutic vaccine candidates. The influenza A virus life cycle lacks DNA intermediates as important safety feature. Different serotypes were generated to ensure efficient prime and boost immunizations. The immune response to vaccination in C57BL/6 mice was characterized by peptide ELISA and IFN-γ ELISpot, demonstrating induction of cell-mediated immunity to HPV16 E6 and E7 oncoproteins. Prophylactic and therapeutic vaccine efficacy was analyzed in the murine HPV16-positive TC-1 tumor challenge model. Subcutaneous (s.c. prime and boost vaccinations of mice with recombinant influenza A serotypes H1N1 and H3N2, followed by challenge with TC-1 cells resulted in complete protection or significantly reduced tumor growth as compared to control animals. In a therapeutic setting, s.c. vaccination of mice with established TC-1 tumors decelerated tumor growth and significantly prolonged survival. Importantly, intralesional vaccine administration induced complete tumor regression in 25% of animals, and significantly reduced tumor growth in 50% of mice. These results suggest recombinant E6E7 influenza viruses as a promising new approach for the development of a therapeutic vaccine against HPV-induced disease.
Kadoglou, Nikolaos P E; Bracke, Frank; Simmers, Tim; Tsiodras, Sotirios; Parissis, John
The interaction of influenza infection with the pathogenesis of acute heart failure (AHF) and the worsening of chronic heart failure (CHF) is rather complex. The deleterious effects of influenza infection on AHF/CHF can be attenuated by specific immunization. Our review aimed to summarize the efficacy, effectiveness, safety, and dosage of anti-influenza vaccination in HF. In this literature review, we searched MEDLINE and EMBASE from January 1st 1966 to December 31st, 2016, for studies examining the association between AHF/CHF, influenza infections, and anti-influenza immunizations. We used broad criteria to increase the sensitivity of the search. HF was a prerequisite for our search. The search fields used included "heart failure," "vaccination," "influenza," "immunization" along with variants of these terms. No restrictions on the type of study design were applied. The most common clinical scenario is exacerbation of pre-existing CHF by influenza infection. Scarce evidence supports a potential positive association of influenza infection with AHF. Vaccinated patients with pre-existing CHF have reduced all-cause morbidity and mortality, but effects are not consistently documented. Immunization with higher antigen quantity may confer additional protection, but such aggressive approach has not been generally advocated. Further studies are needed to delineate the role of influenza infection on AHF/CHF pathogenesis and maintenance. Annual anti-influenza vaccination appears to be an effective measure for secondary prevention in HF. Better immunization strategies and more efficacious vaccines are urgently necessary.
Li, Xi; Miao, Hongyu; Henn, Alicia; Topham, David J.; Wu, Hulin; Zand, Martin S.; Mosmann, Tim R.
Although previous studies have found minimal changes in CD4 T cell responses after vaccination of adults with trivalent inactivated influenza vaccine, daily sampling and monitoring of the proliferation marker Ki-67 have now been used to reveal that a substantial fraction of influenza-specific CD4 T cells respond to vaccination. At 4–6 days after vaccination, there is a sharp rise in the numbers of Ki-67-expressing PBMC that produce IFNγ, IL-2 and/or TNFα in vitro in response to influenza vacc...
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
Hakim, Hana; Gaur, Aditya H; McCullers, Jonathan A
Recent guidance from related regulatory agencies and medical societies supports mandatory vaccination of healthcare workers (HCW) against influenza. At St. Jude Children's Research Hospital, a pediatric oncology referral center, more than 90% of HCWs receive vaccine each year without a policy mandating immunization. Factors associated with HCW uptake of influenza vaccines have not previously been evaluated in a high compliance rate setting. A structured, anonymous, electronic questionnaire was distributed in August 2010 to employees (HCW and non-HCW). Demographics, prior receipt of influenza vaccines, reasons for acceptance or refusal of seasonal and 2009 H1N1 pandemic vaccine, and attitudes on mandatory vaccination were assessed. 95.0% of 925 HCWs and 63.1% of all 3227 qualifying employees responded to the survey. 93.8% and 75.2% of HCW reported receiving seasonal and 2009 H1N1 influenza vaccines, respectively, in the 2009-2010 season. Benefits to self and/or patients were cited as the most frequent reasons for accepting seasonal (83.5% and 78.3%, respectively) and 2009 H1N1 (85.9% and 81.1%, respectively) vaccination. 36.6% of HCWs opposed mandating influenza vaccination; 88.2% and 59.9% of whom reported receiving the seasonal and 2009 H1N1 influenza vaccines, respectively. Violation of freedom of choice and personal autonomy were the most frequently reported reasons for opposition. In this cohort of HCWs with a high influenza vaccination rate, realistic assessments of the potential benefits of vaccination appear to have driven the choice to accept immunization. Despite this, mandating vaccination was viewed unfavorably by a significant minority of vaccinated individuals. Employee concerns over autonomy should be addressed as institutions transition to mandatory vaccination policies. Copyright © 2011 Elsevier Ltd. All rights reserved.
Mak, Donna B; Regan, Annette K; Joyce, Sarah; Gibbs, Robyn; Effler, Paul V
Although influenza vaccination is an important component of antenatal care and is recommended and funded by the Australian government, vaccination uptake has been low. This study compared seasonal influenza vaccination uptake among pregnant Western Australian (WA) women and identified factors associated with vaccination uptake. Adult women who were pregnant during the 2012 and 2013 influenza vaccination seasons were selected at random and invited to complete a computer-assisted telephone interview survey about whether they received influenza vaccination during pregnancy. Data analyses were weighted to the age distribution of women of reproductive age in WA. Multivariate logistic regression was used to identify factors associated with vaccination uptake. Between 2012 and 2013, the proportion of WA women whose antenatal care provider recommended influenza vaccination increased from 37.6 to 62.1% and vaccination uptake increased from 23.0 to 36.5%. The antenatal care provider's advice to have influenza vaccine was the single most important factor associated with vaccination (OR 11.1, 95% CI 7.9-15.5). Most women (63.7%) were vaccinated in general practice, 18.8% in a public hospital antenatal clinic and 11.0% at their workplace. Wanting to protect their infant from infection (91.2%) and having the vaccine recommended by their GP (60.0%) or obstetrician (51.0%) were commonly reported reasons for vaccination; worrying about side effects was a common reason for nonvaccination. To optimise maternal and infant health outcomes, Australian antenatal care providers and services need to incorporate both the recommendation and delivery of influenza vaccination into routine antenatal care. © 2014 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.
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.
Wenlan Alex Chen
Full Text Available Highly pathogenic avian influenza represents a severe public health threat. Over the last decade, the demand for highly efficacious vaccines against avian influenza viruses has grown, especially after the 2013 H7N9 outbreak in China that resulted in over 600 human cases with over 200 deaths. Currently, there are several H5N1 and H7N9 influenza vaccines in clinical trials, all of which employ traditional oil-in-water adjuvants due to the poor immunogenicity of avian influenza virus antigens. In this study, we developed potent recombinant avian influenza vaccine candidates using HyperAcute™ Technology, which takes advantage of naturally-acquired anti-αGal immunity in humans. We successfully generated αGal-positive recombinant protein and virus-like particle vaccine candidates of H5N1 and H7N9 influenza strains using either biological or our novel CarboLink chemical αGal modification techniques. Strikingly, two doses of 100 ng αGal-modified vaccine, with no traditional adjuvant, was able to induce a much stronger humoral response in αGT BALB/c knockout mice (the only experimental system readily available for testing αGal in vivo than unmodified vaccines even at 10-fold higher dose (1000 ng/dose. Our data strongly suggest that αGal modification significantly enhances the humoral immunogenicity of the recombinant influenza vaccine candidates. Use of αGal HyperAcute™ technology allows significant dose-sparing while retaining desired immunogenicity. Our success in the development of highly potent H5N1 and H7N9 vaccine candidates demonstrated the potential of αGal HyperAcute™ technology for the development of vaccines against other infectious diseases.
Choi, Aery; Kim, Yun Kyung; Eun, Byung Wook; Jo, Dae Sun
Purpose Seasonal influenza can be prevented by vaccination. Disease prevention in children aged vaccinate their children, the identification of drivers and barriers to vaccination is essential to increase influenza vaccination coverage. Methods A total of 639 parents participated in the pre- and posteducational survey and 450 parents participated in the study via telephone interviews. The participating parents were asked to rank their agreement with each statement of the survey questionnaire on a scale from 1 (strongly disagree) to 5 (strongly agree), and the scores between pre- and postintervention were compared. Results Before the educational intervention, 105 out of 639 participants reported not to agree to vaccinate their children against influenza. After the intervention, 46 out of the 105 parents changed their opinions about childhood vaccination. The physicians' recommendation received the highest agreement score and was the most important driver to vaccination, whereas the cost of vaccination was the strongest factor for not vaccinating children. In general, the participants significantly changed the agreement scores between pre- and postintervention. However, the unfavorable opinions about vaccination and the convenience of receiving the influenza vaccine did not change significantly. Conclusion The results of this study indicate that a specific educational intervention involving caregivers is very effective in increasing the influenza vaccination coverage of children aged less than 60 months. PMID:29042867
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. Copyright © 2016 Elsevier B.V. All rights reserved.
Gazmararian, Julie A; Orenstein, Walter; Prill, Mila; Hitzhusen, Hannah B; Coleman, Margaret S; Pazol, Karen; Oster, Natalia V
To explore the knowledge and attitudes of mothers of school-aged children toward influenza vaccination and assess what methods of communication about vaccination and its delivery work best among this audience. The authors conducted focus groups with mothers of school-aged children. Prior to the focus groups, investigators agreed on key themes and discussion points. They independently reviewed transcripts using systematic content analysis and came to an agreement on outcome themes. Many study participants had misunderstandings about influenza vaccines and the definition of influenza. A common perception was that flu is a catch-all term for a variety of undefined illnesses, ranging from a severe cold to stomach upset. Few participants saw a societal benefit in vaccinating children to protect other populations (eg, the elderly). This study represents a first step in understanding how mothers perceive influenza vaccination and for crafting effective communication to increase vaccination among school-aged children.
Recurrent influenza outbreak has been a concern for government health institutions in Taiwan. Over 10% of the population is infected by influenza viruses every year, and the infection has caused losses to both health and the economy. Approximately three million free vaccine doses are ordered and administered to high-risk populations at the beginning of flu season to control the disease. The government recommends sharing and redistributing vaccine inventories when shortages occur. While this policy intends to increase inventory flexibility, and has been proven as widely valuable, its impact on vaccine availability has not been previously reported. This study developed an inventory model adapted to vaccination protocols to evaluate government recommended polices under different levels of vaccine production. Demands were uncertain and stratified by ages and locations according to the demographic data in Taiwan. When vaccine supply is sufficient, sharing pediatric vaccine reduced vaccine unavailability by 43% and overstock by 54%, and sharing adult vaccine reduced vaccine unavailability by 9% and overstock by 15%. Redistributing vaccines obtained greater gains for both pediatrics and adults (by 75%). When the vaccine supply is in short, only sharing pediatric vaccine yielded a 48% reduction of unused inventory, while other polices do not improve performances. When implementing vaccination activities for seasonal influenza intervention, it is important to consider mismatches of demand and vaccine inventory. Our model confirmed that sharing and redistributing vaccines can substantially increase availability and reduce unused vaccines.
Full Text Available Recurrent influenza outbreak has been a concern for government health institutions in Taiwan. Over 10% of the population is infected by influenza viruses every year, and the infection has caused losses to both health and the economy. Approximately three million free vaccine doses are ordered and administered to high-risk populations at the beginning of flu season to control the disease. The government recommends sharing and redistributing vaccine inventories when shortages occur. While this policy intends to increase inventory flexibility, and has been proven as widely valuable, its impact on vaccine availability has not been previously reported.This study developed an inventory model adapted to vaccination protocols to evaluate government recommended polices under different levels of vaccine production. Demands were uncertain and stratified by ages and locations according to the demographic data in Taiwan.When vaccine supply is sufficient, sharing pediatric vaccine reduced vaccine unavailability by 43% and overstock by 54%, and sharing adult vaccine reduced vaccine unavailability by 9% and overstock by 15%. Redistributing vaccines obtained greater gains for both pediatrics and adults (by 75%. When the vaccine supply is in short, only sharing pediatric vaccine yielded a 48% reduction of unused inventory, while other polices do not improve performances.When implementing vaccination activities for seasonal influenza intervention, it is important to consider mismatches of demand and vaccine inventory. Our model confirmed that sharing and redistributing vaccines can substantially increase availability and reduce unused vaccines.
Full Text Available Invariant natural killer T (iNKT cells are an “innate-like” T cell lineage that recognize glycolipid rather than peptide antigens by their semi-invariant T cell receptors. Because iNKT cells can stimulate an extensive array of immune responses, there is considerable interest in targeting these cells to enhance human vaccines against a wide range of microbial pathogens. However, long overlooked is the potential to harness iNKT cell antigens as vaccine adjuvants for domestic animal species that express the iNKT cell–CD1d system. In this review, we discuss the prospect of targeting porcine iNKT cells as a strategy to enhance the efficiency of swine influenza vaccines. In addition, we compare the phenotype and tissue distribution of porcine iNKT cells. Finally, we discuss the challenges that must be overcome before iNKT cell agonists can be contemplated for veterinary use in livestock.
Given the burden of illness associated with influenza, vaccination is recommended for individuals at high risk of complications. The live-attenuated influenza vaccine (LAIV) is administered by intranasal spray, thus directly stimulating mucosal immunity. In this review, we aimed to provide evidence for its efficacy and safety in different paediatric populations. We also share the Quebec experience of LAIV use through a publicly funded vaccination program for children with chronic, high-risk conditions. from randomized controlled trials in healthy children and in asthmatics have demonstrated superior efficacy of LAIV over the injectable vaccine (IIV). LAIV is well tolerated: its administration is associated with runny nose and nasal congestion, but not with asthma exacerbations and is well tolerated in children with cystic fibrosis, when compared to IIV. The vaccine is well accepted by children and parents and can easily be part of vaccination clinics in paediatric tertiary care centres targeting children with chronic, high-risk conditions, not leading to immunosuppression. Copyright © 2014 Elsevier Ltd. All rights reserved.
Kjos, Sonia A.; Irving, Stephanie A.; Meece, Jennifer K.; Belongia, Edward A.
Background Studies of influenza vaccine effectiveness in schools have assessed all-cause absenteeism rather than laboratory-confirmed influenza. We conducted an observational pilot study to identify absences due to respiratory illness and laboratory-confirmed influenza in schools with and without school-based vaccination. Methods A local public health agency initiated school-based influenza vaccination in two Wisconsin elementary schools during October 2010 (exposed schools); two nearby schools served as a comparison group (non-exposed schools). Absences due to fever or cough illness were monitored for 12 weeks. During the 4 weeks of peak influenza activity, parents of absent children with fever/cough illness were contacted and offered influenza testing. Results Parental consent for sharing absenteeism data was obtained for 937 (57%) of 1,640 students. Fifty-two percent and 28%, respectively, of all students in exposed and non-exposed schools were vaccinated. Absences due to fever or cough illness were significantly lower in the exposed schools during seven of 12 surveillance weeks. Twenty-seven percent of students at exposed schools and 39% at unexposed schools had one or more days of absence due to fever/cough illness (pabsenteeism due to fever or cough illness, but not absenteeism for other reasons. Although nonspecific, absence due to fever or cough illness may be a useful surrogate endpoint in school-based studies if identification of laboratory confirmed influenza is not feasible. PMID:23991071
Wendelboe, Aaron M; Avery, Catherine; Andrade, Bernardo; Baumbach, Joan; Landen, Michael G
Employees of long-term care facilities (LTCFs) who have contact with residents should be vaccinated against influenza annually to reduce influenza incidence among residents. This investigation estimated the magnitude of the benefit of this recommendation. The New Mexico Department of Health implemented active surveillance in all of its 75 LTCFs during influenza seasons 2006-2007 and 2007-2008. Information about the number of laboratory-confirmed cases of influenza and the proportion vaccinated of both residents and direct-care employees in each facility was collected monthly. LTCFs reporting at least 1 case of influenza (defined alternately by laboratory confirmation or symptoms of influenza-like illness [ILI]) among residents were compared with LTCFs reporting no cases of influenza. Regression modeling was used to obtain adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for the association between employee vaccination coverage and the occurrence of influenza outbreaks. Covariates included vaccination coverage among residents, the staff-to-resident ratio, and the proportion of filled beds. Seventeen influenza outbreaks were reported during this 2-year period of surveillance. Eleven of these were laboratory confirmed (n = 21 residents) and 6 were defined by ILI (n = 40 residents). Mean influenza vaccination coverage among direct-care employees was 51% in facilities reporting outbreaks and 60% in facilities not reporting outbreaks (P = .12). Increased vaccination coverage among direct-care employees was associated with fewer reported outbreaks of laboratory-confirmed influenza (aOR, 0.97 [95% CI, 0.95-0.99]) and ILI (aOR, 0.98 [95% CI, 0.96-1.00]). High vaccination coverage among direct-care employees helps to prevent influenza in LTCFs.
Caldwell, Ronald; Roberts, Craig S; An, Zhijie; Chen, Chieh-I; Wang, Bruce
China has experienced several severe outbreaks of influenza over the past century: 1918, 1957, 1968, and 2009. Influenza itself can be deadly; however, the increase in mortality during an influenza outbreak is also attributable to secondary bacterial infections, specifically pneumococcal disease. Given the history of pandemic outbreaks and the associated morbidity and mortality, we investigated the cost-effectiveness of a PCV7 vaccination program in China from the context of typical and pandemic influenza seasons. A decision-analytic model was employed to evaluate the impact of a 7-valent pneumococcal vaccine (PCV7) infant vaccination program on the incidence, mortality, and cost associated with pneumococcal disease during a typical influenza season (15% flu incidence) and influenza pandemic (30% flu incidence) in China. The model incorporated Chinese data where available and included both direct and indirect (herd) effects on the unvaccinated population, assuming a point in time following the initial introduction of the vaccine where the impact of the indirect effects has reached a steady state, approximately seven years following the implementation of the vaccine program. Pneumococcal disease incidence, mortality, and costs were evaluated over a one year time horizon. Healthcare costs were calculated using a payer perspective and included vaccination program costs and direct medical expenditures from pneumococcal disease. The model predicted that routine PCV7 vaccination of infants in China would prevent 5,053,453 cases of pneumococcal disease and 76,714 deaths in a single year during a normal influenza season.The estimated incremental-cost-effectiveness ratios were ¥12,281 (US$1,900) per life-year saved and ¥13,737 (US$2,125) per quality-adjusted-life-year gained. During an influenza pandemic, the model estimated that routine vaccination with PCV7 would prevent 8,469,506 cases of pneumococcal disease and 707,526 deaths, and would be cost-saving. Routine
Full Text Available The study objective is to estimate the epidemiological and economic impact of vaccine interventions during influenza pandemics in Chicago, and assist in vaccine intervention priorities. Scenarios of delay in vaccine introduction with limited vaccine efficacy and limited supplies are not unlikely in future influenza pandemics, as in the 2009 H1N1 influenza pandemic. We simulated influenza pandemics in Chicago using agent-based transmission dynamic modeling. Population was distributed among high-risk and non-high risk among 0-19, 20-64 and 65+ years subpopulations. Different attack rate scenarios for catastrophic (30.15%, strong (21.96%, and moderate (11.73% influenza pandemics were compared against vaccine intervention scenarios, at 40% coverage, 40% efficacy, and unit cost of $28.62. Sensitivity analysis for vaccine compliance, vaccine efficacy and vaccine start date was also conducted. Vaccine prioritization criteria include risk of death, total deaths, net benefits, and return on investment. The risk of death is the highest among the high-risk 65+ years subpopulation in the catastrophic influenza pandemic, and highest among the high-risk 0-19 years subpopulation in the strong and moderate influenza pandemics. The proportion of total deaths and net benefits are the highest among the high-risk 20-64 years subpopulation in the catastrophic, strong and moderate influenza pandemics. The return on investment is the highest in the high-risk 0-19 years subpopulation in the catastrophic, strong and moderate influenza pandemics. Based on risk of death and return on investment, high-risk groups of the three age group subpopulations can be prioritized for vaccination, and the vaccine interventions are cost saving for all age and risk groups. The attack rates among the children are higher than among the adults and seniors in the catastrophic, strong, and moderate influenza pandemic scenarios, due to their larger social contact network and homophilous
Gasparini, R.; Pozzi, T.; Montomoli, E.; Fragapane, E.; Senatore, F.; Minutello, M.; Podda, A.
Three-hundred and eight outpatient elderly subjects (≥ 65 years) were randomly assigned to receive the MF59-adjuvanted influenza vaccine (FLUAD; n = 204) or a conventional subunit influenza vaccine (AGRIPPAL S1; n = 104) in order to compare the safety and immunogenicity of the two vaccines. Although mild pain at the injection site was reported more frequently by subjects immunised with the adjuvanted vaccine, both vaccines were shown to be safe and well tolerated. The adjuvanted vaccine was more immunogenic as indicated by higher post-immunisation geometric mean titres (GMTs) and by higher proportions of subjects with post-immunisation ≥ four fold increases of antibody titres or subjects with ≥ 1/160 post-immunisation HI titres. These differences, statistically significant for all three strains after immunisation, indicated that, by addition of the MF59 adjuvant emulsion, conventional subunit influenza antigens acquire an enhanced immunogenicity without any clinically significant increase of their reactogenicity
Bradbury, Andrew M [Los Alamos National Laboratory; Velappan, Nileena [Los Alamos National Laboratory; Schmidt, Jurgen G [Los Alamos National Laboratory
M2 is one of the most conserved influenza proteins, and has been widely prospected as a potential universal vaccine target, with protection predominantly mediated by antibodies. In this paper we describe the creation of a humanized single chain Fv from 14C2, a potent monoclonal antibody against M2. We show that the humanized scFv demonstrates similar activity to the parental mAb: it is able to recognize M2 in its native context on cell surfaces and is able to show protective in vitro activity against influenza, and so represents a potential lead antibody candidate for universal prophylactic or therapeutic intervention in influenza.
Yan Mylene L
Full Text Available Abstract Background Influenza virus is a major health concern that has huge impacts on the human society, and vaccination remains as one of the most effective ways to mitigate this disease. Comparing the two types of commercially available Influenza vaccine, the live attenuated virus vaccine is more cross-reactive and easier to administer than the traditional inactivated vaccines. One promising live attenuated Influenza vaccine that has completed Phase I clinical trial is deltaFLU, a deletion mutant lacking the viral Nonstructural Protein 1 (NS1 gene. As a consequence of this gene deletion, this mutant virus can only propagate effectively in cells with a deficient interferon-mediated antiviral response. To demonstrate the manufacturability of this vaccine candidate, a batch bioreactor production process using adherent Vero cells on microcarriers in commercially available animal-component free, serum-free media is described. Results Five commercially available animal-component free, serum-free media (SFM were evaluated for growth of Vero cells in agitated Cytodex 1 spinner flask microcarrier cultures. EX-CELL Vero SFM achieved the highest cell concentration of 2.6 × 10^6 cells/ml, whereas other SFM achieved about 1.2 × 10^6 cells/ml. Time points for infection between the late exponential and stationary phases of cell growth had no significant effect in the final virus titres. A virus yield of 7.6 Log10 TCID50/ml was achieved using trypsin concentration of 10 μg/ml and MOI of 0.001. The Influenza vaccine production process was scaled up to a 3 liter controlled stirred tank bioreactor to achieve a cell density of 2.7 × 10^6 cells/ml and virus titre of 8.3 Log10 TCID50/ml. Finally, the bioreactor system was tested for the production of the corresponding wild type H1N1 Influenza virus, which is conventionally used in the production of inactivated vaccine. High virus titres of up to 10 Log10 TCID50/ml were achieved. Conclusions We describe for the
Paul Thiamjoo Tan
Full Text Available The immune-related evolution of influenza viruses is exceedingly complex and current vaccines against influenza must be reformulated for each influenza season because of the high degree of antigenic drift among circulating influenza strains. Delay in vaccine production is a serious problem in responding to a pandemic situation, such as that of the current H1N1 strain. Immune escape is generally attributed to reduced antibody recognition of the viral hemagglutinin and neuraminidase proteins whose rate of mutation is much greater than that of the internal non-structural proteins. As a possible alternative, vaccines directed at T cell epitope domains of internal influenza proteins, that are less susceptible to antigenic variation, have been investigated.HLA transgenic mouse strains expressing HLA class I A*0201, A*2402, and B*0702, and class II DRB1*1501, DRB1*0301 and DRB1*0401 were immunized with 196 influenza H1N1 peptides that contained residues of highly conserved proteome sequences of the human H1N1, H3N2, H1N2, H5N1, and avian influenza A strains. Fifty-four (54 peptides that elicited 63 HLA-restricted peptide-specific T cell epitope responses were identified by IFN-gamma ELISpot assay. The 54 peptides were compared to the 2007-2009 human H1N1 sequences for selection of sequences in the design of a new candidate H1N1 vaccine, specifically targeted to highly-conserved HLA-restricted T cell epitopes.Seventeen (17 T cell epitopes in PB1, PB2, and M1 were selected as vaccine targets based on sequence conservation over the past 30 years, high functional avidity, non-identity to human peptides, clustered localization, and promiscuity to multiple HLA alleles. These candidate vaccine antigen sequences may be applicable to any avian or human influenza A virus.
Full Text Available 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 effect of the
Kamimura, Akiko; Trinh, Ha N; Weaver, Shannon; Chernenko, Alla; Nourian, Maziar M; Assasnik, Nushean; Nguyen, Hanh
Influenza is a significant worldwide public health issue. Knowledge and perceptions regarding the flu vaccination are associated with whether individuals obtain the vaccination. The purpose of this study was to examine how such perceptions were related to knowledge and self-efficacy regarding influenza and the flu vaccination in Vietnam and the US. College students (n=932) in Vietnam (n=495) and the US (n=437) completed a self-administered survey regarding knowledge and perceptions of influenza vaccinations in September and October 2016. Vietnamese participants reported significantly lower levels of awareness about flu risk, higher levels of negative attitudes toward flu vaccination, lower levels of knowledge about the flu and vaccination, and lower levels of self-efficacy than US participants. Higher levels of flu and flu vaccination knowledge and self-efficacy regarding general responsible health practices were associated with lower levels of negative perceptions of flu risk and attitudes toward vaccination. At the same time, self-efficacy regarding responsible health practices was associated with higher levels of awareness of flu risk and lower levels of negative attitudes toward vaccination. Self-efficacy regarding exercise was associated with lower levels of perceptions of flu risk and higher levels of negative attitudes toward vaccination. Vietnam could benefit from influenza education based on this comparison with the US. In both countries, knowledge and self-efficacy were found to be important factors influencing perceptions of influenza risk and vaccination.
Full Text Available Objectives Influenza is a significant worldwide public health issue. Knowledge and perceptions regarding the flu vaccination are associated with whether individuals obtain the vaccination. The purpose of this study was to examine how such perceptions were related to knowledge and self-efficacy regarding influenza and the flu vaccination in Vietnam and the US. Methods College students (n=932 in Vietnam (n=495 and the US (n=437 completed a self-administered survey regarding knowledge and perceptions of influenza vaccinations in September and October 2016. Results Vietnamese participants reported significantly lower levels of awareness about flu risk, higher levels of negative attitudes toward flu vaccination, lower levels of knowledge about the flu and vaccination, and lower levels of self-efficacy than US participants. Higher levels of flu and flu vaccination knowledge and self-efficacy regarding general responsible health practices were associated with lower levels of negative perceptions of flu risk and attitudes toward vaccination. At the same time, self-efficacy regarding responsible health practices was associated with higher levels of awareness of flu risk and lower levels of negative attitudes toward vaccination. Self-efficacy regarding exercise was associated with lower levels of perceptions of flu risk and higher levels of negative attitudes toward vaccination. Conclusions Vietnam could benefit from influenza education based on this comparison with the US. In both countries, knowledge and self-efficacy were found to be important factors influencing perceptions of influenza risk and vaccination.
Vardeny, Orly; Claggett, Brian; Udell, Jacob A; Packer, Milton; Zile, Michael; Rouleau, Jean; Swedberg, Karl; Desai, Akshay S; Lefkowitz, Martin; Shi, Victor; McMurray, John J V; Solomon, Scott D
This study sought to examine the prevalence and predictors of influenza vaccination among participants in the PARADIGM-HF (Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) study and investigate associations between receiving influenza vaccine and cardiovascular death or heart failure hospitalizations, all-cause hospitalizations, and cardiopulmonary or influenza-related hospitalizations. Influenza is associated with an increased risk for cardiovascular events in patients with heart failure. We used data from the PARADIGM-HF trial in which patients with heart failure were randomized to the angiotensin receptor neprilysin inhibitor LCZ696 (sacubitril/valsartan) or enalapril. We assessed predictors of receiving influenza vaccination, and examined the relationship between influenza vaccination and outcomes in a propensity-adjusted model. Of 8,099 study participants, 1,769 (21%) received influenza vaccination. We observed significant regional variation in vaccination rates, with highest rates in the Netherlands (77.5%), Great Britain (77.2%), and Belgium (67.5%), and lowest rates in Asia (2.6%), with intermediate rates in North America (52.8%). Top predictors of vaccination included enrolling country, white race, implanted defibrillator, older age, lower New York Heart Association functional class, lower heart rate, and a history of diabetes mellitus. Influenza vaccination was associated with a reduced risk for all-cause mortality in propensity-adjusted (hazard ratio: 0.81; 95% confidence interval: 0.67 to 0.97; p = 0.015) models. Influenza vaccination rates varied widely in patients with heart failure with reduced ejection fraction enrolled in the PARADIGM-HF trial, and vaccination was associated with reduced risk for death, although whether this association was causal cannot be determined. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
Alexander, Jeff; Ward, Simone; Mendy, Jason; Manayani, Darly J; Farness, Peggy; Avanzini, Jenny B; Guenther, Ben; Garduno, Fermin; Jow, Lily; Snarsky, Victoria; Ishioka, Glenn; Dong, Xin; Vang, Lo; Newman, Mark J; Mayall, Tim
Influenza virus remains a significant health and social concern in part because of newly emerging strains, such as avian H5N1 virus. We have developed a prototype H5N1 vaccine using a recombinant, replication-competent Adenovirus serotype 4 (Ad4) vector, derived from the U.S. military Ad4 vaccine strain, to express the hemagglutinin (HA) gene from A/Vietnam/1194/2004 influenza virus (Ad4-H5-Vtn). Our hypothesis is that a mucosally-delivered replicating Ad4-H5-Vtn recombinant vector will be safe and induce protective immunity against H5N1 influenza virus infection and disease pathogenesis. The Ad4-H5-Vtn vaccine was designed with a partial deletion of the E3 region of Ad4 to accommodate the influenza HA gene. Replication and growth kinetics of the vaccine virus in multiple human cell lines indicated that the vaccine virus is attenuated relative to the wild type virus. Expression of the HA transgene in infected cells was documented by flow cytometry, western blot analysis and induction of HA-specific antibody and cellular immune responses in mice. Of particular note, mice immunized intranasally with the Ad4-H5-Vtn vaccine were protected against lethal H5N1 reassortant viral challenge even in the presence of pre-existing immunity to the Ad4 wild type virus. Several non-clinical attributes of this vaccine including safety, induction of HA-specific humoral and cellular immunity, and efficacy were demonstrated using an animal model to support Phase 1 clinical trial evaluation of this new vaccine.
Full Text Available Influenza virus remains a significant health and social concern in part because of newly emerging strains, such as avian H5N1 virus. We have developed a prototype H5N1 vaccine using a recombinant, replication-competent Adenovirus serotype 4 (Ad4 vector, derived from the U.S. military Ad4 vaccine strain, to express the hemagglutinin (HA gene from A/Vietnam/1194/2004 influenza virus (Ad4-H5-Vtn. Our hypothesis is that a mucosally-delivered replicating Ad4-H5-Vtn recombinant vector will be safe and induce protective immunity against H5N1 influenza virus infection and disease pathogenesis.The Ad4-H5-Vtn vaccine was designed with a partial deletion of the E3 region of Ad4 to accommodate the influenza HA gene. Replication and growth kinetics of the vaccine virus in multiple human cell lines indicated that the vaccine virus is attenuated relative to the wild type virus. Expression of the HA transgene in infected cells was documented by flow cytometry, western blot analysis and induction of HA-specific antibody and cellular immune responses in mice. Of particular note, mice immunized intranasally with the Ad4-H5-Vtn vaccine were protected against lethal H5N1 reassortant viral challenge even in the presence of pre-existing immunity to the Ad4 wild type virus.Several non-clinical attributes of this vaccine including safety, induction of HA-specific humoral and cellular immunity, and efficacy were demonstrated using an animal model to support Phase 1 clinical trial evaluation of this new vaccine.
Johansen, Laurie Jo; Stenvig, Thomas; Wey, Howard
We examined the relationships between factors (intention, habit, facilitating conditions, and social, cognitive, and affective factors) and nurses' decisions about influenza vaccinations to understand why some get vaccinated while others do not. In a descriptive correlational design, the Triandis model of interpersonal behavior was used to examine the decision of nurses to receive influenza vaccinations. Participants were a random sample (N=193) of registered nurses in North and South Dakota drawn from the respective state nursing licensing board lists. Instrument construction and mail survey procedures followed Dillman's tailored design method. The response rate exceeded 80%. The findings revealed significant, positive correlations among all model variables. Item analysis showed that false beliefs about influenza disease and vaccinations were prevalent and that there was a wide variation in employer support for nurses getting vaccinated. Educational and social marketing strategies may improve nurse's knowledge about influenza disease and vaccine and increase vaccine uptake. Employers should be encouraged to promote and improve influenza vaccine accessibility in the workplace. Additional study is needed to understand how best to strengthen the influence of intention and habit on the decision of nurses to receive influenza vaccinations. © 2011 Wiley Periodicals, Inc.
Li, Xi; Miao, Hongyu; Henn, Alicia; Topham, David J; Wu, Hulin; Zand, Martin S; Mosmann, Tim R
Although previous studies have found minimal changes in CD4 T cell responses after vaccination of adults with trivalent inactivated influenza vaccine, daily sampling and monitoring of the proliferation marker Ki-67 have now been used to reveal that a substantial fraction of influenza-specific CD4 T cells respond to vaccination. At 4-6 days after vaccination, there is a sharp rise in the numbers of Ki-67-expressing PBMC that produce IFNγ, IL-2 and/or TNFα in vitro in response to influenza vaccine or peptide. Ki-67(+) cell numbers then decline rapidly, and 10 days after vaccination, both Ki-67(+) and overall influenza-specific cell numbers are similar to pre-vaccination levels. These results provide a tool for assessing the quality and quantity of CD4 T cell responses to different influenza vaccines, and raise the possibility that the anti-influenza T cell memory response may be qualitatively altered by vaccination, even if the overall memory cell numbers do not change significantly. Copyright © 2012. Published by Elsevier Ltd.
Kim, Yeu-Chun; Song, Jae-Min; Lipatov, Aleksandr S.; Choi, Seong-O; Lee, Jeong Woo; Donis, Ruben O.; Compans, Richard W.; Kang, Sang-Moo; Prausnitz, Mark R.
Effective public health responses to an influenza pandemic require an effective vaccine that can be manufactured and administered to large populations in the shortest possible time. In this study, we evaluated a method for vaccination against avian influenza virus that uses a DNA vaccine for rapid manufacturing and delivered by a microneedle skin patch for simplified administration and increased immunogenicity. We prepared patches containing 700 µm-long microneedles coated with an avian H5 influenza hemagglutinin DNA vaccine from A/Viet Nam/1203/04 influenza virus. The coating DNA dose increased with DNA concentration in the coating solution and the number of dip coating cycles. Coated DNA was released into the skin tissue by dissolution within minutes. Vaccination of mice using microneedles induced higher levels of antibody responses and hemagglutination inhibition titers, and improved protection against lethal infection with avian influenza as compared to conventional intramuscular delivery of the same dose of the DNA vaccine. Additional analysis showed that the microneedle coating solution containing carboxymethylcellulose and a surfactant may have negatively affected the immunogenicity of the DNA vaccine. Overall, this study shows that DNA vaccine delivery by microneedles can be a promising approach for improved vaccination to mitigate an influenza pandemic. PMID:22504442
Eiros-Bouza, Jose Ma; Pérez-Rubio, Alberto
Since the 80s two lineages of type B viruses are co - circulating in the world. Antigenic differences between them are important and it leads to lack of cross-reactivity. The impact on the burden of disease due to influenza B virus, poor foresight in estimating which of the two lineages of B viruses circulate in the season, and the consequent lack of immunity in case of including the wrong strain make that the availability of the quadrivalent vaccine is very useful. The aim of this paper is to analyze the past influenza seasons in Spain to assess the burden of disease, divergence between the vaccine strain and the circulating B and viral characteristics associated with type B in each seasonal epidemic. Review of all reports issued by the Influenza Surveillance System in Spain since the 2003-2004 season to 2012-2013. Over the past influenza seasons, although type A was present mostly, circulation of influenza B virus in each season was observed, even being co - dominant in some of them. In a high number of seasons the divergence between the vaccine strain and the circulating strain lineage has been observed The protective effect of influenza vaccine has varied depending on the type / subtype of influenza virus studied. The vaccine effectiveness against influenza infection by influenza B virus has varied greatly depending on the season analyzed.
Sarah J. Clark, MPH
Full Text Available Vaccination in non-medical settings is recommended as a strategy to increase access to seasonal influenza vaccine. To evaluate change in early-season influenza vaccination setting, we analyzed data from the National Internet Flu Survey. Bivariate comparison of respondent characteristics by location of vaccination was assessed using chi-square tests. Multinomial logistic regression was performed to compare the predicted probability of being vaccinated in medical, retail, and mobile settings in 2012 vs 2013. In both 2012 and 2013, vaccination in medical settings was more likely among elderly adults, those with chronic conditions, and adults with a high school education or less. Adults 18–64 without a chronic condition had a lower probability of vaccination in the medical setting, and higher probability of vaccination in a retail or mobile setting, in 2013 compared to 2012. Adults 18–64 with a chronic condition had no change in their location of flu vaccination. Elderly adults had a lower probability of vaccination in the medical setting, and higher probability of vaccination in a retail setting, in 2013 compared to 2012. Non-medical settings continue to play an increasing role in influenza vaccination of adults, particularly for adults without a chronic condition and elderly adults. Retail and mobile settings should continue to be viewed as important mechanisms to ensure broad access to influenza vaccination.
Fröbert, Ole; Götberg, Matthias; Angerås, Oskar
BACKGROUND: Registry studies and case-control studies have demonstrated that the risk of acute myocardial infarction (AMI) is increased following influenza infection. Small randomized trials, underpowered for clinical end points, indicate that future cardiovascular events can be reduced following...... influenza vaccination in patients with established cardiovascular disease. Influenza vaccination is recommended by international guidelines for patients with cardiovascular disease, but uptake is varying and vaccination is rarely prioritized during hospitalization for AMI. METHODS/DESIGN: The Influenza...... be assigned either to in-hospital influenza vaccination or to placebo. Baseline information is collected from national heart disease registries, and follow-up will be performed using both registries and a structured telephone interview. The primary end point is a composite of time to all-cause death, a new...
to the unvaccinated challenge controls. As well, an increased frequency of T helper memory cells and increased levels of recall IFNγ secretion by tracheobronchial lymph nodes cells were observed. In summary, chitosan SwIAV nanovaccine delivered by IN route elicited strong cross-reactive mucosal IgA and cellular immune responses in the respiratory tract that resulted in a reduced nasal viral shedding and lung virus titers in pigs. Thus, chitosan-based influenza nanovaccine may be an ideal candidate vaccine for use in pigs, and pig is a useful animal model for preclinical testing of particulate IN human influenza vaccines.
Julie E Ledgerwood
Full Text Available The efficacy of current influenza vaccines is limited in vulnerable populations. DNA vaccines can be produced rapidly, and may offer a potential strategy to improve vaccine immunogenicity, indicated by studies with H5 influenza DNA vaccine prime followed by inactivated vaccine boost.Four sites enrolled healthy adults, randomized to receive 2011/12 seasonal influenza DNA vaccine prime (n=65 or phosphate buffered saline (PBS (n=66 administered intramuscularly with Biojector. All subjects received the 2012/13 seasonal inactivated influenza vaccine, trivalent (IIV3 36 weeks after the priming injection. Vaccine safety and tolerability was the primary objective and measurement of antibody response by hemagglutination inhibition (HAI was the secondary objective.The DNA vaccine prime-IIV3 boost regimen was safe and well tolerated. Significant differences in HAI responses between the DNA vaccine prime and the PBS prime groups were not detected in this study.While DNA priming significantly improved the response to a conventional monovalent H5 vaccine in a previous study, it was not effective in adults using seasonal influenza strains, possibly due to pre-existing immunity to the prime, unmatched prime and boost antigens, or the lengthy 36 week boost interval. Careful optimization of the DNA prime-IIV3 boost regimen as related to antigen matching, interval between vaccinations, and pre-existing immune responses to influenza is likely to be needed in further evaluations of this vaccine strategy. In particular, testing this concept in younger age groups with less prior exposure to seasonal influenza strains may be informative.ClinicalTrials.gov NCT01498718.
Asghar, Zahid; Coupland, Carol; Siriwardena, Niroshan
Stroke may be triggered by respiratory infections, including influenza. Influenza vaccination could therefore reduce risk of stroke. Previous studies of this association have shown conflicting results. We aimed to investigate whether influenza vaccination was associated with reduced risk of stroke. We used a self-controlled case series design. The General Practice Research Database (GPRD) was used to extract records of patients aged 18 years or over recorded with stroke (fatal or non-fatal) from September 2001 to May 2009. Statistical modelling with conditional Poisson regression was employed to compute incidence rate ratios (IRR). The incidence rate of stroke in fixed time periods after influenza vaccination was compared with the incidence rate during a baseline period. There were 17,853 eligible individuals who received one or more influenza vaccinations and experienced a stroke during the observation period. The incidence of stroke was significantly reduced in the first 59 days following influenza vaccination compared with the baseline period. We found reductions of 55% (IRR 0.45; 95% CI 0.36-0.57) in the first 1-3 days after vaccination, 36% (0.64; 0.53-0.76) at 4-7 days, 30% (0.70; 0.61-0.79) at 8-14 days, 24% (0.76; 0.70-0.84) at 15-28 days and 17% (0.83; 0.77-0.89) at 29-59 days after vaccination. Early vaccination between 1 September and 15 November showed a greater reduction in IRR compared to later vaccination given after mid-November. Influenza vaccination is associated with a reduction in incidence of stroke. This study supports previous studies which have shown a beneficial association of influenza vaccination for stroke prevention. Copyright © 2015 Elsevier Ltd. All rights reserved.
Full Text Available Background: Influenza vaccine coverage among the Japanese population is less than optimal. Anti-vaccination sentiment exists worldwide, and Japan is no exception. Anti-influenza vaccination activists argue on the internet that influenza vaccine has little or no efficacy and a high risk of side effects, and they warn that people should forgo vaccination. We conducted a qualitative analysis to explore beliefs underlying the messages of anti-influenza vaccination websites, by focusing on the perceived value these beliefs provide to those who hold them. Methods: We conducted online searches in January 2017 using two major Japanese search engines (Google Japan and Yahoo! Japan. Targeted websites were classified as “pro”, “anti”, or “neutral” depending on their claims. We applied a dual analytic approach—inductive thematic analysis and deductive interpretative analysis—to textual data of the anti websites. Results: Of the 113 anti websites, we identified two themes that correspond to beliefs: it is necessary to 1 protect others against risks and exploitation related to influenza vaccination, and 2 educate others about hidden truths and self-determination. Authors of anti websites ascribed two values (people's “safety” and one's own “self-esteem” to their beliefs. Discussion: Website authors may engage in anti-vaccination activities because they want to feel they are virtuous, saving people from harm caused by vaccination, and to boost their self-esteem, thinking “I am enlightening uninformed people.” The anti-vaccination beliefs of website authors were considered to be strong. In promoting vaccination, it would be better not to target outright vaccine refusers, such as the authors of anti-vaccination websites; it is preferable to target vaccine-hesitant people who are more amenable to changing their attitudes toward vaccination. We discuss possible means of promoting vaccination in that target population. Keywords
Full Text Available Background: Patients with diabetes who contract influenza are at higher risk of complications, such as hospitalization and death. Patients with diabetes are three times more likely to die from influenza complications than those without diabetes. Racial disparities among patients with diabetes in preventive health services have not been extensively studied. Objective: To compare influenza vaccination rates among African Americans and Whites patients with diabetes and investigate factors that might have an impact on racial disparities in the receipt of influenza vaccinations. Methods: A secondary data analysis of 47,283 (unweighted patients with diabetes from the 2011 Behavioral Risk Factor Surveillance System survey (BRFSS (15,902,478 weighted was performed. The survey respondents were asked whether they received an influenza vaccination in the last twelve months. We used logistic regression to estimate the odds of receiving the influenza vaccine based on race. Results: The results indicated a significantly lower proportion of African Americans respondents (50% reported receiving the influenza vaccination in the last year when compared with Whites respondents (61%. Age, gender, education, health care coverage, health care cost, and employment status were found to significantly modify the effect of race on receiving the influenza vaccination. Conclusions: This study found a significant racial disparity in influenza vaccination rates in adults with diabetes with higher rates in Whites compared to African Americans individuals. The public health policies that target diabetes patients in general and specifically African Americans in the 65+ age group, women, and homemakers, may be necessary to diminish the racial disparity in influenza vaccination rates between African Americans and Whites diabetics.
Gefenaite, Giedre; Tacken, Margot; Bos, Jens; Stirbu-Wagner, Irina; Korevaar, Joke C.; Stolk, Ronald P.; Wolters, Bert; Bijl, Marc; Postma, Maarten J.; Wilschut, Jan; Nichol, Kristin L.; Hak, Eelko
Background: Because of variability in published A(H1N1)pdm09 influenza vaccine effectiveness estimates, we aimed to assess the effectiveness of MF59-adjuvanted A(H1N1)pdm09 vaccine in a matched case-control study. Objectives: We aimed to assess the effectiveness of MF59- adjuvanted A(H1N1)pdm09
Effects of influenza plus pneumococcal conjugate vaccination versus influenza vaccination alone in preventing respiratory tract infections in children : a randomized, double-blind, placebo-controlled trial
Jansen, Angelique G S C; Sanders, Elisabeth A M; Hoes, Arno W; van Loon, Anton M; Hak, Eelko
OBJECTIVE: To evaluate the effects of influenza vaccination with or without heptavalent pneumococcal conjugate vaccination on respiratory tract infections (RTIs) in children. STUDY DESIGN: This was a randomized, double-blind, placebo-controlled trial comprising 579 children age 18 to 72 months with
Kunze, Ursula; Böhm, Gabriela; Groman, Ernest
Austria's position on influenza vaccination is unique. Generally it is recommended for everyone, and specifically for those over the age of 50 years and all children between 6 months and 5 years. However, the vaccination rate among the general public is one of the lowest in the world (Austria during a period of almost 30 years, from 1982 to 2011. Data presented in this study were obtained from three sources. Between 1982 and 1992, Austria showed little change in its low proportion of vaccinations (from 20 to 23 doses/1000); from 1992 to 1995, the proportion increased to 52 doses/1000, retaining its status as one of the low-use countries. By 2003, the proportion had increased to 127 doses/1000, but Austria remained one of the three lowest-use Western European countries. Between 2007 and 2011/2012, a steady decrease to 81 doses/1000 was observed. The Austrian population, and parts of the medical system, have shown distinct ignorance regarding the prevention and control of influenza over past decades. Possible reasons for this development are discussed. Copyright © 2013 Elsevier Ltd. All rights reserved.
Prematunge, Chatura; Corace, Kimberly; McCarthy, Anne; Nair, Rama C; Roth, Virginia; Suh, Kathryn N; Garber, Gary
Influenza is a major concern across healthcare environments. Annual vaccination of healthcare workers (HCW) remains a key mode of influenza prevention in healthcare settings. Yet influenza vaccine coverage among HCWs continues to be below recommended targets, in pandemic and non-pandemic settings. Thus, the primary objective of this analysis is to identify motivators and barriers to pandemic (panINFLU) and seasonal influenza vaccination (sINFLU) through the qualitative analysis of HCW provided reasons driving HCW's personal vaccination decisions. Data were collected from a multi-professional sample of HCWs via a cross-sectional survey study, conducted at a tertiary-care hospital in Ontario, Canada. HCW provided and ranked qualitative reasons for personal (1) panINFLU (pH1N1) and (2) sINFLU (2008/2009 season) vaccine uptake and avoidance were used to identify key vaccination motivators and barriers through content analysis methodology. Most HCW vaccination motivators and barriers were found to be similar for panINFLU and sINFLU vaccines. Personal motivators had the greatest impact on vaccination (panINFLU 29.9% and sINFLU 33.9%). Other motivators included preventing influenza in loved ones, patients, and community, and awareness of HCW role in influenza transmission. In contrast, concerns of vaccine safety and limited HCW knowledge of influenza vaccines (panINFLU 46.2% and sINFLU 37.3%). HCW vaccination during the pandemic was motivated by panINFLU related fear, epidemiology, and workplace pro-vaccination policies. HCW perceptions of accelerated panINFLU vaccine development and vaccine safety compromises, negative views of external sources (i.e. media, pharmaceutical companies, and regulatory agencies) and pandemic management strategies were barriers specific to panINFLU vaccine. HCW panINFLU and sINFLU vaccine coverage can increase if future vaccination programs (1) highlight personal vaccination benefits (2) emphasize the impact HCW non-vaccination on family
Kroneman, M.; Essen, G.A. van; Paget, J.
This paper examines influenza vaccine coverage using a population base of an average of 2300 persons in each of four European countries (Germany, Spain, Poland and Sweden). The reasons for non-vaccination of those in the high-risk groups were explored by questionnaire. The vaccine coverage rate
Full Text Available 50% survival, or 100% survival with adjuvant, compared with 10% survival after vaccination with a commercially available H 1 N 1 vaccine. TMV-HA is an effective dose-sparing influenza vaccine, using a single-step process to rapidly generate large...
Turner, Nikki; Pierse, Nevil; Bissielo, Ange; Huang, Q Sue; Baker, Michael G; Widdowson, Marc-Alain; Kelly, Heath
Few studies report the effectiveness of trivalent inactivated influenza vaccine (TIV) in preventing hospitalisation for influenza-confirmed respiratory infections. Using a prospective surveillance platform, this study reports the first such estimate from a well-defined ethnically diverse population in New Zealand (NZ). A case test-negative design was used to estimate propensity adjusted vaccine effectiveness. Patients with a severe acute respiratory infection (SARI), defined as a patient of any age requiring hospitalisation with a history of a fever or a measured temperature ≥38°C and cough and onset within the past 7 days, admitted to public hospitals in South and Central Auckland were eligible for inclusion in the study. Cases were SARI patients who tested positive for influenza, while non-cases (controls) were SARI patients who tested negative. Results were adjusted for the propensity to be vaccinated and the timing of the influenza season. The propensity and season adjusted vaccine effectiveness (VE) was estimated as 39% (95% CI 16;56). The VE point estimate against influenza A (H1N1) was lower than for influenza B or influenza A (H3N2) but confidence intervals were wide and overlapping. Estimated VE was 59% (95% CI 26;77) in patients aged 45-64 years but only 8% (-78;53) in those aged 65 years and above. Prospective surveillance for SARI has been successfully established in NZ. This study for the first year, the 2012 influenza season, has shown low to moderate protection by TIV against influenza positive hospitalisation. Copyright © 2014 Elsevier Ltd. All rights reserved.
Turner, Nikki; Pierse, Nevil; Bissielo, Ange; Huang, Q Sue; Baker, Michael; Widdowson, Marc-Alain; Kelly, Heath
Background Few studies report the effectiveness of trivalent inactivated influenza vaccine (TIV) in preventing hospitalisation for influenza-confirmed respiratory infections. Using a prospective surveillance platform, this study reports the first such estimate from a well-defined ethnically diverse population in New Zealand (NZ). Methods A case test-negative study was used to estimate propensity adjusted vaccine effectiveness. Patients with a severe acute respiratory infection (SARI), defined as a patient of any age requiring hospitalization with a history of a fever or a measured temperature ≥38°C and cough and onset within the past 7 days, admitted to public hospitals in Central, South and East Auckland were eligible for inclusion in the study. Cases were SARI patients who tested positive for influenza, while non-cases (controls) were SARI patients who tested negative. Results were adjusted for the propensity to be vaccinated and the timing of the influenza season Results The propensity and season adjusted vaccine effectiveness (VE) was estimated as 37% (95% CI 18;51). The VE point estimate against influenza A (H1N1) was higher than for influenza B or influenza A (H3N2) but confidence intervals were wide and overlapping. Estimated VE was 51% (95% CI 28;67) in patients aged 18-64 years but only 6% (95% CI -51;42) in those aged 65 years and above. Conclusion Prospective surveillance for SARI has been successfully established in NZ . This study for the first year, the 2012 influenza season, has shown low to moderate protection by TIV against hospitalisation for laboratory-confirmed influenza. PMID:24768730
O'Leary, Sean T; Pyrzanowski, Jennifer; Brewer, Sarah E; Barnard, Juliana; Beaty, Brenda; Donnelly, Meghan; Mazzoni, Sara; Dempsey, Amanda F
Our objectives were to describe the receipt of influenza and tetanus-diphtheria-acellular pertussis (Tdap) vaccines among postpartum women and their close contacts and the factors associated with cocooning. A survey between February 2013 and April 2013 of 613 postpartum women from 9 obstetrics practices assessed vaccine receipt among respondents and close contacts, demographics and 5 domains of health beliefs (benefits, barriers, susceptibility, severity and social norms). Multivariable models assessed the association of these factors with Tdap or influenza "cocooning," defined as the mother plus at least 1 close contact of her newborn receiving the vaccine. The response rate was 45%; 61% of mothers reported that they and at least 1 close contact of their newborn had received influenza vaccine, and 67% reported this for Tdap. Infants whose mothers received influenza vaccine had a mean of 2.8 close contacts who also received influenza vaccine versus a mean of 0.9 contacts for infants whose mothers did not receive influenza vaccine (P referent to White). Maternal vaccination and obstetrician recommendation are associated with infant cocooning. Interventions to increase cocooning of infants should focus on encouraging strong provider recommendations, increasing maternal knowledge of disease risk and addressing identified barriers. Reasons for possible racial/ethnic differences should be further explored.
Barington, T; Skettrup, M; Juul, L
children and adults. Despite its potential importance, the possible influence of preexisting immunity to the components of such conjugates on the vaccination response in humans has been addressed by few studies. To study this issue, we randomized 82 healthy adult volunteers into six groups and vaccinated......Recently, conjugate vaccines containing Haemophilus influenzae type b capsular polysaccharide (HibCP) coupled to protein carriers were introduced for use in infants and certain adult risk groups. Similar conjugate vaccines against other capsulated bacteria are currently under development for both......CP-TT, P = 0.00002; HibCP-TT and then HibCP-DT, P = 0.06) as well as to HibCP itself. Possible mechanisms behind this non-epitope-specific suppression and its relevance for vaccine development are discussed....
Okuhara, Tsuyoshi; Ishikawa, Hirono; Kato, Mio; Okada, Masafumi; Kiuchi, Takahiro
Influenza vaccine coverage among the Japanese population is less than optimal. Anti-vaccination sentiment exists worldwide, and Japan is no exception. Anti-influenza vaccination activists argue on the internet that influenza vaccine has little or no efficacy and a high risk of side effects, and they warn that people should forgo vaccination. We conducted a qualitative analysis to explore beliefs underlying the messages of anti-influenza vaccination websites, by focusing on the perceived value these beliefs provide to those who hold them. We conducted online searches in January 2017 using two major Japanese search engines (Google Japan and Yahoo! Japan). Targeted websites were classified as "pro", "anti", or "neutral" depending on their claims. We applied a dual analytic approach-inductive thematic analysis and deductive interpretative analysis-to textual data of the anti websites. Of the 113 anti websites, we identified two themes that correspond to beliefs: it is necessary to 1) protect others against risks and exploitation related to influenza vaccination, and 2) educate others about hidden truths and self-determination. Authors of anti websites ascribed two values (people's "safety" and one's own "self-esteem") to their beliefs. Website authors may engage in anti-vaccination activities because they want to feel they are virtuous, saving people from harm caused by vaccination, and to boost their self-esteem, thinking "I am enlightening uninformed people." The anti-vaccination beliefs of website authors were considered to be strong. In promoting vaccination, it would be better not to target outright vaccine refusers, such as the authors of anti-vaccination websites; it is preferable to target vaccine-hesitant people who are more amenable to changing their attitudes toward vaccination. We discuss possible means of promoting vaccination in that target population.
In this review, the most important viruses associated with human and animal influenza are reported. These include Influenza A,B and C. Influenza viruses are members of the family Orthomyxoviridae. Influenza A virus being the most pathogenic and wide spread with many subtypes has constantly cause epidemics in several ...
Demirdogen Cetinoglu, Ezgi; Uzaslan, Esra; Sayıner, Abdullah; Cilli, Aykut; Kılınc, Oguz; Sakar Coskun, Aysın; Hazar, Armağan; Kokturk, Nurdan; Filiz, Ayten; Polatli, Mehmet
Previous reports have shown that vaccination rates of adult at-risk populations are low in Turkey. There are differing reports with regards to the effectiveness of the influenza and the pneumococcal polysaccharide vaccine (PPSV23) on the clinical outcomes of community acquired pneumonia (CAP). The purpose of this study was to analyze the influenza (FV) and pneumococcal vaccination (PV) status, the factors that influence the receipt of influenza/pneumococcal vaccine and the effects of prior vaccination on the clinical outcomes in adults hospitalized with CAP. Patients hospitalized with CAP between March 2009 and October 2013 and registered at the web-based Turkish Thoracic Society Pneumonia Database (TURCAP) were included in this multicentric, observational study. Of a total of 787 cases, data were analyzed for 466 patients for whom self-reported information on PV and FV was available. In this adult population with CAP, the vaccination rate with both the pneumococcal and influenza vaccines was found to be 6%. Prior FV was found to be the sole variable that was associated with the receipt of PV [OR 17.8, 95% CI (25-75:8.56-37.01), p pneumonia severity index (PSI) score ≥ 90, CURB-65 score ≥3 and multilobar involvement, but not the vaccination status, were identified as independent determinants of ICU admission. This study showed that, among patients hospitalized with CAP, the FV and/or PV rates are low. Prior vaccination does not appear to significantly affect the clinical outcomes.
Full Text Available Abstract Background The 2009 pandemic of influenza A (H1N1 infection has alerted many governments to make preparedness plan to control the spread of influenza A (H1N1 infection. Vaccination for influenza is one of the most important primary preventative measures to reduce the disease burden. Our study aims to assess the willingness of nurses who work for the community nursing service (CNS in Hong Kong on their acceptance of influenza A (H1N1 influenza vaccination. Methods 401 questionnaires were posted from June 24, 2009 to June 30, 2009 to community nurses with 67% response rate. Results of the 267 respondents on their willingness to accept influenza A (H1N1 vaccine were analyzed. Results Twenty-seven percent of respondents were willing to accept influenza vaccination if vaccines were available. Having been vaccinated for seasonable influenza in the previous 12 months were significantly independently associated with their willingness to accept influenza A (H1N1 vaccination (OR = 4.03; 95% CI: 2.03-7.98. Conclusions Similar to previous findings conducted in hospital healthcare workers and nurses, we confirmed that the willingness of community nurses to accept influenza A (H1N1 vaccination is low. Future studies that evaluate interventions to address nurses' specific concerns or interventions that aim to raise the awareness among nurses on the importance of influenza A (H1N1 vaccination to protect vulnerable patient populations is needed.
Kamal, Ram P; Blanchfield, Kristy; Belser, Jessica A; Music, Nedzad; Tzeng, Wen-Pin; Holiday, Crystal; Burroughs, Ashley; Sun, Xiangjie; Maines, Taronna R; Levine, Min Z; York, Ian A
Avian influenza viruses of the H7 hemagglutinin (HA) subtype present a significant public health threat, as evidenced by the ongoing outbreak of human A(H7N9) infections in China. When evaluated by hemagglutination inhibition (HI) and microneutralization (MN) assays, H7 viruses and vaccines are found to induce lower level of neutralizing antibodies (nAb) than do their seasonal counterparts, making it difficult to develop and evaluate prepandemic vaccines. We have previously shown that purified recombinant H7 HA appear to be poorly immunogenic in that they induce low levels of HI and MN antibodies. In this study, we immunized mice with whole inactivated reverse genetics reassortant (RG) viruses expressing HA and neuraminidase (NA) from 3 different H7 viruses [A/Shanghai/2/2013(H7N9), A/Netherlands/219/2003(H7N7), and A/New York/107/2003(H7N2)] or with human A(H1N1)pdm09 (A/California/07/2009-like) or A(H3N2) (A/Perth16/2009) viruses. Mice produced equivalent titers of antibodies to all viruses as measured by enzyme-linked immunosorbent assay (ELISA). However, the antibody titers induced by H7 viruses were significantly lower when measured by HI and MN assays. Despite inducing very low levels of nAb, H7 vaccines conferred complete protection against homologous virus challenge in mice, and the serum antibodies directed against the HA head region were capable of mediating protection. The apparently low immunogenicity associated with H7 viruses and vaccines may be at least partly related to measuring antibody titers with the traditional HI and MN assays, which may not provide a true measure of protective immunity associated with H7 immunization. This study underscores the need for development of additional correlates of protection for prepandemic vaccines. IMPORTANCE H7 avian influenza viruses present a serious risk to human health. Preparedness efforts include development of prepandemic vaccines. For seasonal influenza viruses, protection is correlated with antibody
Duerrwald, Ralf; Schlegel, Michael; Bauer, Katja; Vissiennon, Théophile; Wutzler, Peter; Schmidtke, Michaela
Recent epidemiological developments demonstrated that gene segments of swine influenza A viruses can account for antigenic changes as well as reduced drug susceptibility of pandemic influenza A viruses. This raises questions about the efficacy of preventive measures against swine influenza A viruses. Here, the protective effect of vaccination was compared with that of prophylactic Tamiflu® treatment against two Eurasian swine influenza A viruses. 11-week-old pigs were infected by aerosol nebulisation with high doses of influenza virus A/swine/Potsdam/15/1981 (H1N1/1981, heterologous challenge to H1N1 vaccine strain) and A/swine/Bakum/1832/2000 (H1N2/2000, homologous challenge to H1N2 vaccine strain) in two independent trials. In each trial (i) 10 pigs were vaccinated twice with a trivalent vaccine (RESPIPORC® FLU3; 28 and 7 days before infection), (ii) another 10 pigs received 150 mg/day of Tamiflu® for 5 days starting 12 h before infection, and (iii) 12 virus-infected pigs were left unvaccinated and untreated and served as controls. Both viruses replicated efficiently in porcine respiratory organs causing influenza with fever, dyspnoea, and pneumonia. Tamiflu® treatment as well as vaccination prevented clinical signs and significantly reduced virus shedding. Whereas after homologous challenge with H1N2/2000 no infectious virus in lung and hardly any lung inflammation were detected, the virus titre was not and the lung pathology was only partially reduced in H1N1/1981, heterologous challenged pigs. Tamiflu® application did not affect these study parameters. In conclusion, all tested preventive measures provided protection against disease. Vaccination additionally prevented virus replication and histopathological changes in the lung of homologous challenged pigs.
Full Text Available Recent epidemiological developments demonstrated that gene segments of swine influenza A viruses can account for antigenic changes as well as reduced drug susceptibility of pandemic influenza A viruses. This raises questions about the efficacy of preventive measures against swine influenza A viruses. Here, the protective effect of vaccination was compared with that of prophylactic Tamiflu® treatment against two Eurasian swine influenza A viruses. 11-week-old pigs were infected by aerosol nebulisation with high doses of influenza virus A/swine/Potsdam/15/1981 (H1N1/1981, heterologous challenge to H1N1 vaccine strain and A/swine/Bakum/1832/2000 (H1N2/2000, homologous challenge to H1N2 vaccine strain in two independent trials. In each trial (i 10 pigs were vaccinated twice with a trivalent vaccine (RESPIPORC® FLU3; 28 and 7 days before infection, (ii another 10 pigs received 150 mg/day of Tamiflu® for 5 days starting 12 h before infection, and (iii 12 virus-infected pigs were left unvaccinated and untreated and served as controls. Both viruses replicated efficiently in porcine respiratory organs causing influenza with fever, dyspnoea, and pneumonia. Tamiflu® treatment as well as vaccination prevented clinical signs and significantly reduced virus shedding. Whereas after homologous challenge with H1N2/2000 no infectious virus in lung and hardly any lung inflammation were detected, the virus titre was not and the lung pathology was only partially reduced in H1N1/1981, heterologous challenged pigs. Tamiflu® application did not affect these study parameters. In conclusion, all tested preventive measures provided protection against disease. Vaccination additionally prevented virus replication and histopathological changes in the lung of homologous challenged pigs.
Duerrwald, Ralf; Schlegel, Michael; Bauer, Katja; Vissiennon, Théophile; Wutzler, Peter; Schmidtke, Michaela
Recent epidemiological developments demonstrated that gene segments of swine influenza A viruses can account for antigenic changes as well as reduced drug susceptibility of pandemic influenza A viruses. This raises questions about the efficacy of preventive measures against swine influenza A viruses. Here, the protective effect of vaccination was compared with that of prophylactic Tamiflu® treatment against two Eurasian swine influenza A viruses. 11-week-old pigs were infected by aerosol nebulisation with high doses of influenza virus A/swine/Potsdam/15/1981 (H1N1/1981, heterologous challenge to H1N1 vaccine strain) and A/swine/Bakum/1832/2000 (H1N2/2000, homologous challenge to H1N2 vaccine strain) in two independent trials. In each trial (i) 10 pigs were vaccinated twice with a trivalent vaccine (RESPIPORC® FLU3; 28 and 7 days before infection), (ii) another 10 pigs received 150 mg/day of Tamiflu® for 5 days starting 12 h before infection, and (iii) 12 virus-infected pigs were left unvaccinated and untreated and served as controls. Both viruses replicated efficiently in porcine respiratory organs causing influenza with fever, dyspnoea, and pneumonia. Tamiflu® treatment as well as vaccination prevented clinical signs and significantly reduced virus shedding. Whereas after homologous challenge with H1N2/2000 no infectious virus in lung and hardly any lung inflammation were detected, the virus titre was not and the lung pathology was only partially reduced in H1N1/1981, heterologous challenged pigs. Tamiflu® application did not affect these study parameters. In conclusion, all tested preventive measures provided protection against disease. Vaccination additionally prevented virus replication and histopathological changes in the lung of homologous challenged pigs. PMID:23630601
Won Suk Choi
Full Text Available The effectiveness of the 2011-2012 seasonal influenza vaccine was evaluated in adult Korean populations with regard to how well it could prevent laboratory-confirmed influenza and influenza-related complications.A retrospective case-control and retrospective cohort study was conducted among patients who visited four selected hospitals from September 2011 to May 2012. The analysis included 1,130 laboratory-confirmed influenza patients. For each influenza case, one control patient was chosen at a ratio of 1:1. A control was defined as an age group-matched patient who visited the same hospital with influenza-like illness within 48 hours of symptom onset but for whom laboratory tests were negative for influenza. Age group and visit date were matched between the cases and controls. Vaccine effectiveness (VE was defined as [100 × (1-odds ratio for influenza in vaccinated versus non-vaccinated persons]. The patients with laboratory-confirmed influenza were followed for at least one month through reviewing the medical records and conducting a telephone interview.The VE of the 2011-2012 seasonal influenza vaccine was 3.8% [95% confidence interval (CI, -16.5% to 20.6%] for preventing laboratory-confirmed influenza, -16.1% (95% CI, -48.3 to 9.1 for influenza A and 26.2% (95% CI, -2.6 to 46.2 for influenza B. The age-specific adjusted VE was 0.3% (95% CI, -29.4 to 23.1 among participants aged 19 to 49 years, 11.9% (95% CI, -34.3 to 42.2 among those aged 50 to 64 years and -3.9% (-60.1 to 32.5 among those aged ≥65 years. The adjusted VE for preventing any influenza-related complications was -10.7% (95% CI, -41.1% to 42.2%.The 2011-2012 seasonal influenza vaccine was not effective in preventing laboratory-confirmed influenza or influenza-related complications in adult Korean populations.
Influenza, rHA, vaccine, baculovirus, insect cells, production, pandemic preparedness
Influenza (or flu) is a highly contagious, acute viral respiratory disease that occurs seasonally in most parts of the world and is caused by influenza viruses. Influenza
Jackson, Michael L.; Phillips, C. Hallie; Benoit, Joyce; Jackson, Lisa A.; Gaglani, Manjusha; Murthy, Kempapura; McLean, Huong Q.; Belongia, Edward A.; Malosh, Ryan; Zimmerman, Richard; Flannery, Brendan
Background In addition to preventing hospitalizations and deaths due to influenza, influenza vaccination programs can reduce the burden of outpatient visits for influenza. We estimated the incidence of medically-attended influenza at three geographically diverse sites in the United States, and the cases averted by vaccination, for the 2013/14 through 2015/16 influenza seasons. Methods We defined surveillance populations at three sites from the United States Influenza Vaccine Effectiveness Network. Among these populations, we identified outpatient visits laboratory-confirmed influenza via active surveillance, and identified all outpatient visits for acute respiratory illness from healthcare databases. We extrapolated the total number of outpatient visits for influenza from the proportion of surveillance visits with a positive influenza test. We combined estimates of incidence, vaccine coverage, and vaccine effectiveness to estimate outpatient visits averted by vaccination. Results Across the three sites and seasons, incidence of medically attended influenza ranged from 14 to 54 per 1,000 population. Incidence was highest in children aged 6 months to 9 years (33 to 70 per 1,000) and lowest in adults aged 18-49 years (21 to 27 per 1,000). Cases averted ranged from 9 per 1,000 vaccinees (Washington, 2014/15) to 28 per 1,000 (Wisconsin, 2013/14). Discussion Seasonal influenza epidemics cause a considerable burden of outpatient medical visits. The United States influenza vaccination program has caused meaningful reductions in outpatient visits for influenza, even in years when the vaccine is not well-matched to the dominant circulating influenza strain. PMID:29249545
Full Text Available This study retrospectively reviewed the effectiveness of a vaccination program for hospital workers in a large tertiary care hospital, quantified influenza-induced absenteeism, and examined the factors determining the costs and benefits of this program. Absenteeism among high risk hospital workers was increased by 35% (P=0.001 during the virulent influenza epidemic of 1987–88. Benefits, measured as the value of sick time avoided, compared with costs, including materials, occupational nursing staff time, employee time during vaccination, and time lost due to adverse reactions, revealed a net benefit of $39.23 per vaccinated employee. Sensitivity analyses highlighted vaccine efficacy and absenteeism due to influenza and adverse reactions to vaccination as the most important factors; with time lost due to adverse reactions as much as 0.013 days per vaccinated employee and a vaccine efficacy of 70%, net positive benefits could be achieved if influenza-induced absenteeism is 0.5% or greater of paid employee time during the epidemic season. The results suggested that the net cost-benefit of a hospital employee vaccination program to decrease both employee morbidity and nosocomial influenza among patients, would be increased by active promotion of the vaccination program, especially for employees in high risk areas.
Xu, Xiyan; Lindstrom, Stephen E; Shaw, Michael W; Smith, Catherine B; Hall, Henrietta E; Mungall, Bruce A; Subbarao, Kanta; Cox, Nancy J; Klimov, Alexander
During the 2001-2002 influenza season, human influenza A (H1N2) reassortant viruses were detected globally. The hemagglutinin (HA) of these H1N2 viruses was similar to that of the A/New Caledonia/20/99 (H1N1) vaccine strain both antigenically and genetically, while their neuraminidase (NA) was antigenically and genetically related to that of recent human influenza H3N2 reference viruses such as A/Moscow/10/99. All six internal genes of the H1N2 reassortants originated from an H3N2 virus. After being detected only in eastern Asia during the past 10 years, Influenza B/Victoria/2/87 lineage viruses reappeared in many countries outside of Asia in 2001. Additionally, reassortant influenza B viruses possessing an HA similar to that of B/Shandong/7/97, a recent B/Victoria/2/87 lineage reference strain, and an NA closely related to that of B/Sichuan/379/99, a recent B/Yamagata/16/88 lineage reference strain, were isolated globally and became the predominant influenza B epidemic strain. The current influenza vaccine is expected to provide good protection against H1N2 viruses because it contains A/New Caledonia/20/99 (H1N1) and A/Panama/2007/99 (H3N2) like viruses whose H1 HA or N2 NA are antigenically similar to those of recent circulating H1N2 viruses. On the other hand, widespread circulation of influenza B Victoria lineage viruses required inclusion of a strain from this lineage in influenza vaccines for the 2002-2003 season.
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, W.K.; Azziz-Baumgartner, E.; Bashir, U.; Cox, N.J.; Fasce, R.; Giovanni, M.; Grohmann, G.; Huang, S.; Katz, J.; Mironenko, A.; Mokhtari-Azad, T.; Sasono, P.M.; Rahman, M.; Sawanpanyalert, P.; Siqueira, M.; Waddell, A.L.; Waiboci, L.; Wood, J.; Zhang, W.; Ziegler, T.; Paget, W.J.; et al.,
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
Pedersen, T.I.; Howitz, Michael Frantz; Andersen, Christian Østergaard
P>The introduction of Haemophilus influenzae type b (Hib) vaccine into the Danish childhood vaccination programme in 1993 may have influenced the epidemiology of H. influenzae meningitis (i.e. increasing frequency of other non-vaccine types; presentation in other age groups). Based on nationwide...... infected with Hib, two cases (13%) were identified as true vaccine failures. Six patients (9%) died; one premature infant infected with serotype f and five adults (age 83-96 years) with non-typeable H. influenzae. Hearing loss was reported in 16% of the surviving children and in 10% of the surviving adults....... The presence of a lung focus was an independent prognostic factor for an unfavourable outcome (p 0.03). In conclusion, meningitis caused by Hib has been infrequent in Denmark after introduction of the Hib vaccine in the childhood vaccination programme, and no increase in meningitis cases due to non-b type H...
The squalene oil-in-water emulsion MF-59 adjuvant was developed initially to enhance the immunogenicity of influenza vaccines in populations such as children and adults with known suboptimal response. Developed in the 1990s, it was initially licensed in Europe for use in seasonal influenza vaccine in the elderly. Since that time, both Avian and p2009H1N1 vaccines have also been developed. Overall, more than 30,000 individuals have participated in clinical trials of MF-59 adjuvanted vaccine and more than 160 million doses of licensed vaccine have been administered. Safety and effectiveness data from clinical trials and observation studies attest to the safety of MF-59 and to its ability to enhance the effectiveness of influenza vaccines in children and the elderly. Copyright © 2014 Elsevier Ltd. All rights reserved.
Loeb, Mark; Russell, Margaret L; Manning, Vanessa; Fonseca, Kevin; Earn, David J D; Horsman, Gregory; Chokani, Khami; Vooght, Mark; Babiuk, Lorne; Schwartz, Lisa; Neupane, Binod; Singh, Pardeep; Walter, Stephen D; Pullenayegum, Eleanor
Whether vaccinating children with intranasal live attenuated influenza vaccine (LAIV) is more effective than inactivated influenza vaccine (IIV) in providing both direct protection in vaccinated persons and herd protection in unvaccinated persons is uncertain. Hutterite colonies, where members live in close-knit, small rural communities in which influenza virus infection regularly occurs, offer an opportunity to address this question. To determine whether vaccinating children and adolescents with LAIV provides better community protection than IIV. A cluster randomized blinded trial conducted between October 2012 and May 2015 over 3 influenza seasons. (ClinicalTrials.gov: NCT01653015). 52 Hutterite colonies in Alberta and Saskatchewan, Canada. 1186 Canadian children and adolescents aged 36 months to 15 years who received the study vaccine and 3425 community members who did not. Children were randomly assigned according to community in a blinded manner to receive standard dosing of either trivalent LAIV or trivalent IIV. The primary outcome was reverse transcriptase polymerase chain reaction-confirmed influenza A or B virus in all participants (vaccinated children and persons who did not receive the study vaccine). Mean vaccine coverage among children in the LAIV group was 76.9% versus 72.3% in the IIV group. Influenza virus infection occurred at a rate of 5.3% (295 of 5560 person-years) in the LAIV group versus 5.2% (304 of 5810 person-years) in the IIV group. The hazard ratio comparing LAIV with IIV for influenza A or B virus was 1.03 (95% CI, 0.85 to 1.24). The study was conducted in Hutterite communities, which may limit generalizability. Immunizing children with LAIV does not provide better community protection against influenza than IIV. The Canadian Institutes for Health Research.
Imburgia, Teresa M; Hendrix, Kristin S; Donahue, Kelly L; Sturm, Lynne A; Zimet, Gregory D
U.S. estimates of seasonal influenza (flu) vaccine uptake in 2014-2015 were 62% for 5-12year olds, dropping to 47% for 13-17year olds. The Healthy People 2020 goal for these age groups is 80%. It is important to understand factors associated with influenza vaccination, especially for those ages where rates begin to decline. The objective of this study was to identify factors associated with influenza vaccination acceptance in 9-13year old children. An online U.S. survey of mothers of children aged 9-13 assessed children's influenza vaccine uptake in the previous season, healthcare utilization, sociodemographics, and vaccine attitudes. Multivariable logistic regression identified independent predictors of influenza vaccine status. There were 2363 respondents (Mean age=38years old). Referent children were 57% female and 66% non-minority race/ethnicity with a mean age of 10.6years. By maternal report, 59% of children had received an influenza vaccine in the previous season. Predictors of influenza vaccine uptake included a recommendation or strong recommendation from a health care provider, seeing a health care provider in the past year, positive attitudes regarding the influenza vaccine, and being a minority race. Child gender, age, insurance coverage, and whether the child had a regular healthcare provider were not associated with influenza vaccine uptake (p=n.s.). This sample reported overall rates of influenza vaccine uptake similar to national surveillance data, but still lower than national goals. Provider recommendations along with health attitudes and seeing a health care provider were associated with vaccine uptake. Promising interventions may include more directive physician messaging for influenza vaccine uptake in youth, encouraging more regular well-child visits during the adolescent years, and promoting influenza vaccination at alternative sites. Copyright © 2017 Elsevier Ltd. All rights reserved.
M. IQBAL, M. NISAR, ANWARUL-HAQ, S. NOOR AND Z. J. GILL
Full Text Available Bird flu vaccine from H5N1 strain of avian influenza virus was prepared with two concentrations of adjuvant (Montanide ISA 70MVG. Two vaccines (I and II were prepared containing 50 and 60% Montanide, respectively. Immune response of both the vaccines as single, as well as booster, dose was evaluated in layer birds through haemagglutination inhibition test. Single dose of both vaccines showed poor immune response, while booster dose gave better response with both the vaccines. However, the vaccine prepared with 60% Montanide provided better immune response compared with the vaccine containing 50% montanide.
Dhakal, Santosh; Renu, Sankar; Ghimire, Shristi; Shaan Lakshmanappa, Yashavanth; Hogshead, Bradley T; Feliciano-Ruiz, Ninoshkaly; Lu, Fangjia; HogenEsch, Harm; Krakowka, Steven; Lee, Chang Won; Renukaradhya, Gourapura J
useful animal model for preclinical testing of particulate IN human influenza vaccines.
Pillsbury, Alexis; Quinn, Helen; Cashman, Patrick; Leeb, Alan; Macartney, Kristine
Australia's novel, active surveillance system, AusVaxSafety, monitors the post-market safety of vaccines in near real time. We analysed cumulative surveillance data for children aged 6 months to 4 years who received seasonal influenza vaccine in 2015 and/or 2016 to determine: adverse event following immunisation (AEFI) rates by vaccine brand, age and concomitant vaccine administration. Parent/carer reports of AEFI occurring within 3 days of their child receiving an influenza vaccine in sentinel immunisation clinics were solicited by Short Message Service (SMS) and/or email-based survey. Retrospective data from 2 years were combined to examine specific AEFI rates, particularly fever and medical attendance as a proxy for serious adverse events (SAE), with and without concomitant vaccine administration. As trivalent influenza vaccines (TIV) were funded in Australia's National Immunisation Program (NIP) in 2015 and quadrivalent (QIV) in 2016, respectively, we compared their safety profiles. 7402 children were included. Data were reported weekly through each vaccination season; no safety signals or excess of adverse events were detected. More children who received a concomitant vaccine had fever (7.5% versus 2.8%; p vaccine was associated with the highest increase in AEFI rates among children receiving a specified concomitant vaccine: 30.3% reported an AEFI compared with 7.3% who received an influenza vaccine alone (p safety profiles included low and expected AEFI rates (fever: 4.3% for TIV compared with 3.2% for QIV (p = .015); injection site reaction: 1.9% for TIV compared with 3.0% for QIV (p safety profile between brands. Active participant-reported data provided timely vaccine brand-specific safety information. Our surveillance system has particular utility in monitoring the safety of influenza vaccines, given that they may vary in composition annually. Copyright © 2017 Elsevier Ltd. All rights reserved.
Goot, van der A.J.; Koch, G.; Jong, de M.C.M.; Boven, van R.M.
Recent outbreaks of highly pathogenic avian influenza (HPAI) viruses in poultry and their threatening zoonotic consequences emphasize the need for effective control measures. Although vaccination of poultry against avian influenza provides a potentially attractive control measure, little is known
Hak, Eelko; Knol, Lisanne M; Wilschut, Jan C; Postma, Maarten J
To assess the annual productivity loss among hospital healthcare workers attributable to influenza and to estimate the costs and economic benefits of a vaccination programme from the perspective of the the employer. Cost-benefit analysis. The percentage of work loss due to influenza was determined using monthly age and gender specific figures for productivity loss among healthcare workers of the University Medical Center Groningen (UMCG), the Netherlands over the period January 2006-June 2008. Influenza periods were determined on the basis of national surveillance data. The average increase in productivity loss in these periods was estimated by comparison with the periods outside influenza seasons. The direct costs of productivity loss from the perspective of the employer were estimated using the friction cost method. In the sensitivity analyses various modelling parameters were varied, such as the vaccination coverage. In the UMCG, with approximately 9,400 employees, the estimated annual costs associated with productivity loss due to influenza before the introduction of the yearly influenza vaccination program were € 675,242 or on average, € 72 per employee. The economic benefits of the current vaccination program with a vaccination coverage of 24% with a vaccine effectiveness of 71% were estimated at € 89,858 or € 10 per employee. The nett economic benefits of a vaccination program with a target vaccination coverage of 70% with a vaccine effectiveness of 71% were estimated at € 244,325 or € 26 per employee. This modelling study performed from the perspective of the employer showed that an annual influenza vaccination programme for hospital personnel can save costs.
Szilagyi, Peter G; Schaffer, Stanley; Rand, Cynthia M; Goldstein, Nicolas P N; Vincelli, Phyllis; Hightower, A Dirk; Younge, Mary; Eagan, Ashley; Blumkin, Aaron; Albertin, Christina S; DiBitetto, Kristine; Yoo, Byung-Kwang; Humiston, Sharon G
We aimed to evaluate the effect of school-located influenza vaccination (SLIV) on adolescents' influenza vaccination rates. In 2015-2016, we performed a cluster-randomized trial of adolescent SLIV in middle/high schools. We selected 10 pairs of schools (identical grades within pairs) and randomly allocated schools within pairs to SLIV or usual care control. At eight suburban SLIV schools, we sent parents e-mail notifications about upcoming SLIV clinics and promoted online immunization consent. At two urban SLIV schools, we sent parents (via student backpack fliers) paper immunization consent forms and information about SLIV. E-mails were unavailable at these schools. Local health department nurses administered nasal or injectable influenza vaccine at dedicated SLIV clinics and billed insurers. We compared influenza vaccination rates at SLIV versus control schools using school directories to identify the student sample in each school. We used the state immunization registry to determine receipt of influenza vaccination. The final sample comprised 17,650 students enrolled in the 20 schools. Adolescents at suburban SLIV schools had higher overall influenza vaccination rates than did adolescents at control schools (51% vs. 46%, p < .001; adjusted odds ratio = 1.27, 95% confidence interval 1.18-1.38, controlling for vaccination during the prior two seasons). No effect of SLIV was noted among urbanschools on multivariate analysis. SLIV did not substitute for vaccinations in primary care or other settings; in suburban settings, SLIV was associated with increased vaccinations in primary care or other settings (adjusted odds ratio = 1.10, 95% confidence interval 1.02-1.19). SLIV in this community increased influenza vaccination rates among adolescents attending suburban schools. Copyright © 2018. Published by Elsevier Inc.
Barington, T; Gyhrs, A; Kristensen, Kim
hundred forty-four infants were vaccinated with HibCP-TT at 5 and 6 months. They were randomized into three groups that received TT as part of a diphtheria-tetanus-polio vaccine at either 6 and 7 months (group A), 5 and 6 months (group B), or 4 and 5 months (group C). Maternally acquired TT antibodies...
Full Text Available Abstract Background In cell culture-based influenza vaccine production the monitoring of virus titres and cell physiology during infection is of great importance for process characterisation and optimisation. While conventional virus quantification methods give only virus titres in the culture broth, data obtained by fluorescence labelling of intracellular virus proteins provide additional information on infection dynamics. Flow cytometry represents a valuable tool to investigate the influences of cultivation conditions and process variations on virus replication and virus yields. Results In this study, fluorescein-labelled monoclonal antibodies against influenza A virus matrix protein 1 and nucleoprotein were used for monitoring the infection status of adherent Madin-Darby canine kidney cells from bioreactor samples. Monoclonal antibody binding was shown for influenza A virus strains of different subtypes (H1N1, H1N2, H3N8 and host specificity (human, equine, swine. At high multiplicity of infection in a bioreactor, the onset of viral protein accumulation in adherent cells on microcarriers was detected at about 2 to 4 h post infection by flow cytometry. In contrast, a significant increase in titre by hemagglutination assay was detected at the earliest 4 to 6 h post infection. Conclusion It is shown that flow cytometry is a sensitive and robust method for the monitoring of viral infection in fixed cells from bioreactor samples. Therefore, it is a valuable addition to other detection methods of influenza virus infection such as immunotitration and RNA hybridisation. Thousands of individual cells are measured per sample. Thus, the presented method is believed to be quite independent of the concentration of infected cells (multiplicity of infection and total cell concentration in bioreactors. This allows to perform detailed studies on factors relevant for optimization of virus yields in cell cultures. The method could also be used for process
Radl, J.; Hoogeveen, C.M.; Wall Bake, A.W.L. van den; Mestecky, J.
Chemicals/CAS: hemagglutinin, 37333-12-3; sialidase, 9001-67-6; Antibodies, Monoclonal; Antibodies, Viral; Hemagglutinins, Viral; Immunoglobulin A; Immunoglobulin G; Influenza Vaccine; Neuraminidase, EC 22.214.171.124
Groenwold, R H H; Hoes, A W; Nichol, K L; Hak, E
BACKGROUND: The validity of non-randomized studies using healthcare databases is often challenged because they lack information on potentially important confounders, such as functional health status and socioeconomic status. In a study quantifying the effects of influenza vaccination among
When health professionals prepare pro-influenza vaccination materials for publication online, we recommend they check for readability using readability assessment tools and improve the text for easy reading if necessary.
Pedersen, T.I.; Howitz, M.; Andersen, Christian Østergaard
P>The introduction of Haemophilus influenzae type b (Hib) vaccine into the Danish childhood vaccination programme in 1993 may have influenced the epidemiology of H. influenzae meningitis (i.e. increasing frequency of other non-vaccine types; presentation in other age groups). Based on nationwide...... registration, clinical information and laboratory findings were collected from all 65 confirmed cases of H. influenzae meningitis during the period 1994-2005. Twenty-nine patients (45%) were 24 years old [median 62 years (range 25...... infected with Hib, two cases (13%) were identified as true vaccine failures. Six patients (9%) died; one premature infant infected with serotype f and five adults (age 83-96 years) with non-typeable H. influenzae. Hearing loss was reported in 16% of the surviving children and in 10% of the surviving adults...
Çiftci, Fatma; Şen, Elif; Demir, Nalan; Çiftci, Orçun; Erol, Serhat; Kayacan, Oya
Vaccination of healthcare personnel (HCP) is an effective measure for preventing the spread of influenza among at-risk patients. This study was conducted to determine influenza vaccination rates and activities among HCP working at a tertiary healthcare setting. This study included 470 HCP (85 physicians, 134 nurses, 53 healthcare assistants, 44 paramedics, 47 medical secretaries, and 107 auxillary staff members) working at the emergency, cardiology, chest diseases, and internal medicine departments with the largest volume of patients with vaccination indication of two large university hospitals with similar medical practices and work environment. Each participant completed an anonymous questionnaire form. A total of 470 HCP participated in the survey. The compliance rate of the HCP to participate in the survey was 93.6%. Of these, 26.7% had been vaccinated against influenza. Vaccination in the survey year was significantly associated with having regular influenza vaccinations (OR 48.66; 95% CI:[25.09-94.369]; P<.01); having an educational level of college or higher (OR 2.07; 95% CI:[1.03-4.15]; P<.05); being a physician (OR 4.25; 95% CI:[1.28-14.07]; P< .05); and a professional experience of more than 5 years (OR 2.02; 95%CI:[1.13-5.62]; P< .05). Physicians recommended and prescribed the influenza vaccine significantly more frequently than the pneumococcal vaccine (37.6% vs 30.6%, P = .03, 25.9% vs 17.6%, P = .001, respectively). Among all HCP, the reasons for vaccination included having the opinion that the vaccine provides a partial protection against the infection (75.2%), reduces work force loss (48.8%), reduces the rates of death and severe conditions like pneumonia (43.2%), and reduces hospitalization (40.8%). The HCP had been vaccinated to protect family members (81.6%), people around (51.2%), herself/himself (47.2%), and patients (28%) fom infection. The reasons of not getting vaccinated against influenza among HCP included fear of vaccine's adverse
Full Text Available Abstract Background Most countries recommend that healthcare workers (HCWs are vaccinated seasonally against influenza in order to protect themselves and patients. However, in many cases coverage remains low. A range of strategies have been implemented to increase uptake. Qualitative evidence can help in understanding the context of interventions, including why interventions may fail to achieve the desired effect. This study aimed to synthesise evidence on HCWs’ perceptions and experiences of vaccination for seasonal influenza. Methods Systematic review of qualitative evidence. We searched MEDLINE, EMBASE and CINAHL and included English-language studies which reported substantive qualitative data on the vaccination of HCWs for seasonal influenza. Findings were synthesised thematically. Results Twenty-five studies were included in the review. HCWs may be motivated to accept vaccination to protect themselves and their patients against infection. However, a range of beliefs may act as barriers to vaccine uptake, including concerns about side-effects, scepticism about vaccine effectiveness, and the belief that influenza is not a serious illness. HCWs value their autonomy and professional responsibility in making decisions about vaccination. The implementation of interventions to promote vaccination uptake may face barriers both from HCWs’ personal beliefs and from the relationships between management and employees within the targeted organisations. Conclusions HCWs’ vaccination behaviour needs to be understood in the context of HCWs’ relationships with each other, with management and with patients. Interventions to promote vaccination should take into account both the individual beliefs of targeted HCWs and the organisational context within which they are implemented.
Vassilieva, Elena V; Wang, Shelly; Li, Song; Prausnitz, Mark R; Compans, Richard W
Recent studies indicated that in elderly individuals, statin therapy is associated with a reduced response to influenza vaccination. The present study was designed to determine effects on the immune response to influenza vaccination induced by statin administration in a mouse model, and investigate potential approaches to improve the outcome of vaccination on the background of statin therapy. We fed middle aged BALB/c mice a high fat "western" diet (WD) alone or supplemented with atorvastatin (AT) for 14 weeks, and control mice were fed with the regular rodent diet. Mice were immunized with a single dose of subunit A/Brisbane/59/07 (H1N1) vaccine, either systemically or with dissolving microneedle patches (MNPs). We observed that a greater age-dependent decline in the hemagglutinin inhibition titers occurred in systemically-immunized mice than in MNP- immunized mice. AT dampened the antibody response in the animals vaccinated by either route of vaccine delivery. However, the MNP-vaccinated AT-treated animals had ~20 times higher total antibody levels to the influenza vaccine than the systemically vaccinated group one month postvaccination. We propose that microneedle vaccination against influenza provides an approach to ameliorate the immunosuppressive effect of statin therapy observed with systemic immunization.
Judith C Maro
Full Text Available Managing emerging vaccine safety signals during an influenza pandemic is challenging. Federal regulators must balance vaccine risks against benefits while maintaining public confidence in the public health system.We developed a multi-criteria decision analysis model to explore regulatory decision-making in the context of emerging vaccine safety signals during a pandemic. We simulated vaccine safety surveillance system capabilities and used an age-structured compartmental model to develop potential pandemic scenarios. We used an expert-derived multi-attribute utility function to evaluate potential regulatory responses by combining four outcome measures into a single measure of interest: 1 expected vaccination benefit from averted influenza; 2 expected vaccination risk from vaccine-associated febrile seizures; 3 expected vaccination risk from vaccine-associated Guillain-Barre Syndrome; and 4 expected change in vaccine-seeking behavior in future influenza seasons.Over multiple scenarios, risk communication, with or without suspension of vaccination of high-risk persons, were the consistently preferred regulatory responses over no action or general suspension when safety signals were detected during a pandemic influenza. On average, the expert panel valued near-term vaccine-related outcomes relative to long-term projected outcomes by 3:1. However, when decision-makers had minimal ability to influence near-term outcomes, the response was selected primarily by projected impacts on future vaccine-seeking behavior.The selected regulatory response depends on how quickly a vaccine safety signal is identified relative to the peak of the pandemic and the initiation of vaccination. Our analysis suggested two areas for future investment: efforts to improve the size and timeliness of the surveillance system and behavioral research to understand changes in vaccine-seeking behavior.
Chon, W. James; Kadambi, Pradeep V.; Harland, Robert C.; Thistlethwaite, J. Richard; West, Bradford L.; Udani, Suneel; Poduval, Rajiv; Josephson, Michelle A.
Background and objectives: Influenza infection in transplant recipients is often associated with significant morbidity. Surveys were conducted in 1999 and 2009 to find out if the influenza vaccination practices in the U.S. transplant programs had changed over the past 10 years.
Keck, Patricia C.; Ynalvez, Marcus Antonius; Gonzalez, Hector F.; Castillo, Keila D.
Seasonal influenza is recognized as a significant health burden to children and is a cause of excess school absenteeism in children. In 2008, the Advisory Committee on Immunization Practices recommended annual influenza vaccination for all children 6 months to 18 years of age. School nurses influence participation in this recommendation by…
Vickers, Elizabeth R; McClure, David L; Naleway, Allison L; Jacobsen, Steven J; Klein, Nicola P; Glanz, Jason M; Weintraub, Eric S; Belongia, Edward A
Influenza-like illness and inflammation are known risk factors for venous thromboembolism (VTE), which includes deep vein thrombosis (DVT) and pulmonary embolism (PE). However, few studies have characterized the risk of VTE following influenza vaccination. We examined VTE risk after vaccination in adults 50years old and older within the Vaccine Safety Datalink (VSD). We used the self-controlled case series method to determine the risk of VTE among age-eligible adults who received influenza vaccine (with or without pandemic H1N1) and experienced a VTE during the months of September through December in 2007 through 2012. Presumptive VTE cases were identified among VSD participants using diagnostic codes, diagnostic tests, and oral anticoagulant prescription. Potential cases were validated by medical record review. The VTE incidence rate ratio was calculated among confirmed cases for the risk window 1 to 10days after vaccination relative to all other person-time from September through December. Of the 1,488 presumptive cases identified, 508 were reviewed, of which 492 (97%) were confirmed cases of VTE. The analysis included 396 incident, confirmed cases. Overall, there was no increased risk of VTE in the 1 to 10days after influenza vaccination (IRR=0.89, 95% CI 0.69-1.17) compared to the control period. Results were similar when all person-time was censored before vaccination. A post hoc analysis showed an increased risk among current tobacco smokers (IRR=2.57, 95% CI 1.06-6.23). No clustering of VTE was observed in the 1-42days after vaccination. Overall, there was no evidence that inactivated influenza vaccine was associated with VTE in adults ≥50years old. An increased risk was found among current smokers in a post hoc analysis. These findings are consistent with previous research and support the safety of annual vaccination in this population. Copyright © 2017 Elsevier Ltd. All rights reserved.
George, Meena; Farooq, Masiha; Dang, Thi; Cortes, Bernadette; Liu, Jonathan; Maranga, Luis
The majority of influenza vaccines are manufactured using embryonated hens' eggs. The potential occurrence of a pandemic outbreak of avian influenza might reduce or even eliminate the supply of eggs, leaving the human population at risk. Also, the egg-based production technology is intrinsically cumbersome and not easily scalable to provide a rapid worldwide supply of vaccine. In this communication, the production of a cell culture (Madin-Darby canine kidney (MDCK)) derived live attenuated influenza vaccine (LAIV) in a fully disposable platform process using a novel Single Use Bioreactor (SUB) is presented. The cell culture and virus infection was maintained in a disposable stirred tank reactor with PID control of pH, DO, agitation, and temperature, similar to traditional glass or stainless steel bioreactors. The application of this technology was tested using MDCK cells grown on microcarriers in proprietary serum free medium and infection with 2006/2007 seasonal LAIV strains at 25-30 L scale. The MDCK cell growth was optimal at the agitation rate of 100 rpm. Optimization of this parameter allowed the cells to grow at a rate similar to that achieved in the conventional 3 L glass stirred tank bioreactors. Influenza vaccine virus strains, A/New Caledonia/20/99 (H1N1 strain), A/Wisconsin/67/05 (H3N2 strain), and B/Malaysia/2506/04 (B strain) were all successfully produced in SUB with peak virus titers > or =8.6 log(10) FFU/mL. This result demonstrated that more than 1 million doses of vaccine can be produced through one single run of a small bioreactor at the scale of 30 L and thus provided an alternative to the current vaccine production platform with fast turn-around and low upfront facility investment, features that are particularly useful for emerging and developing countries and clinical trial material production.
PURPOSE AND OBJECTIVES: The patients using immunosuppressive agents are considered at high risk for acquiring different infections. Accordingly, international guidelines recommend vaccinating such patients against influenza and pneumococcal organisms. The aims of this study were two-fold: (1) to assess the influenza and pneumococcal vaccination uptake among our rheumatology outpatients who are immunosuppressed; (2) to identify the factors influencing immunisation uptake among our sample of patients.
Dombkowski, Kevin J; Cowan, Anne E; Reeves, Sarah L; Foley, Matthew R; Dempsey, Amanda F
We sought to: (1) explore the feasibility of using email for seasonal influenza vaccination reminders to parents of adolescents and (2) assess influenza vaccination rates among adolescents whose parents were randomized to either receive or not receive email reminders. Email addresses were obtained for parents of patients 10-18years from 4 practices in Michigan. Addresses were randomized to either receive email reminders, or not. Reminder messages were sent during October 2012-March 2013 (Season 1) and October 2013-March 2014 (Season 2). Vaccination status was determined 60days following the last email reminder for each season using the statewide Michigan Care Improvement Registry (MCIR); per protocol bivariate and multivariate logistic regression analyses were conducted to evaluate reminder notification. After email cleaning, testing, and matching with MCIR, approximately half of email addresses (2348 of 5312 in Season 1; 3457 of 6549 in Season 2) were randomized. Bivariate analyses found that influenza vaccination within 60days after notification date was similar among those notified (34%) versus not notified (29%) in both Season 1 (p=0.06) and Season 2 (39% vs. 37%, p=0.20). However, multivariate models adjusted for season, site, and receipt of notification in two seasons found a higher likelihood of influenza vaccination among children that received notification (aOR=1.28, 95% CI=1.09, 1.51); in addition, differences in influenza vaccination were also observed between practice sites (range: p=0.15 to pemail influenza vaccine reminders to parents of adolescents are feasible, but not without complications. Our study demonstrates that email reminders from practices can yield increases in influenza vaccination rates among adolescents. Practices should consider email as an option for influenza reminders and establish business practices for collecting and maintaining patient email addresses. This study is registered at www.ClinicalTrials.gov id #NCT01732315. Copyright
McElhaney, J.E.; Beran, J.; Devaster, J.M.; Esen, M.; Launay, O.; Leroux-Roels, G.; Ruiz-Palacios, G.M.; Essen, G.A. van; Caplanusi, A.; Claeys, C.; Durand, C.; Duval, X.; Idrissi, M. El; Falsey, A.R.; Feldman, G.; Frey, S.E.; Galtier, F.; Hwang, S.J.; Innis, B.L.; Kovac, M.; Kremsner, P.; McNeil, S.; Nowakowski, A.; Richardus, J.H.; Trofa, A.; Oostvogels, L.; Verheugt, F.W.; et al.,
BACKGROUND: We aimed to compare AS03-adjuvanted inactivated trivalent influenza vaccine (TIV) with non-adjuvanted TIV for seasonal influenza prevention in elderly people. METHODS: We did a randomised trial in 15 countries worldwide during the 2008-09 (year 1) and 2009-10 (year 2) influenza seasons.
Knight-Jones, T. J. D.; Edmond, K.; Gubbins, S.; Paton, D. J.
Despite the universal importance of vaccines, approaches to human and veterinary vaccine evaluation differ markedly. For human vaccines, vaccine efficacy is the proportion of vaccinated individuals protected by the vaccine against a defined outcome under ideal conditions, whereas for veterinary vaccines the term is used for a range of measures of vaccine protection. The evaluation of vaccine effectiveness, vaccine protection assessed under routine programme conditions, is largely limited to human vaccines. Challenge studies under controlled conditions and sero-conversion studies are widely used when evaluating veterinary vaccines, whereas human vaccines are generally evaluated in terms of protection against natural challenge assessed in trials or post-marketing observational studies. Although challenge studies provide a standardized platform on which to compare different vaccines, they do not capture the variation that occurs under field conditions. Field studies of vaccine effectiveness are needed to assess the performance of a vaccination programme. However, if vaccination is performed without central co-ordination, as is often the case for veterinary vaccines, evaluation will be limited. This paper reviews approaches to veterinary vaccine evaluation in comparison to evaluation methods used for human vaccines. Foot-and-mouth disease has been used to illustrate the veterinary approach. Recommendations are made for standardization of terminology and for rigorous evaluation of veterinary vaccines. PMID:24741009
Mereckiene, J; Cotter, S; D'Ancona, F; Giambi, C; Nicoll, A; Levy-Bruhl, D; Lopalco, P L; Weber, J T; Johansen, K; Dematte, L; Salmaso, S; Stefanoff, P; Greco, D; Dorleans, F; Polkowska, A; O'Flanagan, D
In 2009 the second cross-sectional web-based survey was undertaken by the Vaccine European New Integrated Collaboration Effort (VENICE) project across 27 European Union (EU) member states (MS), Norway and Iceland (n=29) to determine changes in official national seasonal influenza vaccination policies since a survey undertaken in 2008 and to compare the estimates of vaccination coverage between countries using data obtained from both surveys. Of 27 responding countries, all recommended vaccination against seasonal influenza to the older adult population. Six countries recommended vaccination of children aged between six months and <18 years old. Most countries recommended influenza vaccination for those individuals with chronic medical conditions. Recommendations for vaccination of healthcare workers (HCW) in various settings existed in most, but not all countries. Staff in hospitals and long-term care facilities were recommended vaccination in 23 countries, and staff in out-patient clinics in 22 countries. In the 2009 survey, the reported national estimates on vaccine coverage varied by country and risk group, ranging from 1.1% - 82.6% for the older adult population; to between 32.9% -71.7% for clinical risk groups; and from 13.4% -89.4% for HCW. Many countries that recommend the influenza vaccination do not monitor the coverage in risk groups. In 2008 and 2009 most countries recommended influenza vaccination for the main risk groups. However, despite general consensus and recommendations for vaccination of high risk groups, many countries do not achieve high coverage in these groups. The reported vaccination coverage still needs to be improved in order to achieve EU and World Health Organization goals.
In 2009 the second cross-sectional web-based survey was undertaken by the Vaccine European New Integrated Collaboration Effort (VENICE) project across 27 European Union (EU) member states (MS), Norway and Iceland (n=29) to determine changes in official national seasonal influenza vaccination policies since a survey undertaken in 2008 and to compare the estimates of vaccination coverage between countries using data obtained from both surveys. Of 27 responding countries, all recommended vaccination against seasonal influenza to the older adult population. Six countries recommended vaccination of children aged between six months and <18 years old. Most countries recommended influenza vaccination for those individuals with chronic medical conditions. Recommendations for vaccination of healthcare workers (HCW) in various settings existed in most, but not all countries. Staff in hospitals and long-term care facilities were recommended vaccination in 23 countries, and staff in out-patient clinics in 22 countries. In the 2009 survey, the reported national estimates on vaccine coverage varied by country and risk group, ranging from 1.1% - 82.6% for the older adult population; to between 32.9% -71.7% for clinical risk groups; and from 13.4% -89.4% for HCW. Many countries that recommend the influenza vaccination do not monitor the coverage in risk groups. In 2008 and 2009 most countries recommended influenza vaccination for the main risk groups. However, despite general consensus and recommendations for vaccination of high risk groups, many countries do not achieve high coverage in these groups. The reported vaccination coverage still needs to be improved in order to achieve EU and World Health Organization goals.
Poehling, Katherine A.; Blocker, Jill; Ip, Edward H.; Peters, Timothy R.; Wolfson, Mark
Objective We sought to describe the 2009–2010 seasonal influenza vaccine coverage of college students. Participants 4090 college students from eight North Carolina universities participated in a confidential, web-based survey in October-November 2009. Methods Associations between self-reported 2009–2010 seasonal influenza vaccination and demographic characteristics, campus activities, parental education, and email usage were assessed by bivariate analyses and by a mixed-effects model adjusting for clustering by university. Results Overall, 20% of students (range 14%–30% by university) reported receiving 2009–2010 seasonal influenza vaccine. Being a freshman, attending a private university, having a college-educated parent, and participating in academic clubs/honor societies predicted receipt of influenza vaccine in the mixed-effects model. Conclusions The self-reported 2009–2010 influenza vaccine coverage was one-quarter of the 2020 Healthy People goal (80%) for healthy persons 18–64 years of age. College campuses have the opportunity to enhance influenza vaccine coverage among its diverse student populations. PMID:23157195
Full Text Available Human influenza virus isolates generally grow poorly in embryonated chicken eggs. Hence, gene reassortment of influenza A wild type (wt viruses is performed with a highly egg adapted donor virus, A/Puerto Rico/8/1934 (PR8, to provide the high yield reassortant (HYR viral 'seeds' for vaccine production. HYR must contain the hemagglutinin (HA and neuraminidase (NA genes of wt virus and one to six 'internal' genes from PR8. Most studies of influenza wt and HYRs have focused on the HA gene. The main objective of this study is the identification of the molecular signature in all eight gene segments of influenza A HYR candidate vaccine seeds associated with high growth in ovo.The genomes of 14 wt parental viruses, 23 HYRs (5 H1N1; 2, 1976 H1N1-SOIV; 2, 2009 H1N1pdm; 2 H2N2 and 12 H3N2 and PR8 were sequenced using the high-throughput sequencing pipeline with big dye terminator chemistry.Silent and coding mutations were found in all internal genes derived from PR8 with the exception of the M gene. The M gene derived from PR8 was invariant in all 23 HYRs underlining the critical role of PR8 M in high yield phenotype. None of the wt virus derived internal genes had any silent change(s except the PB1 gene in X-157. The highest number of recurrent silent and coding mutations was found in NS. With respect to the surface antigens, the majority of HYRs had coding mutations in HA; only 2 HYRs had coding mutations in NA.In the era of application of reverse genetics to alter influenza A virus genomes, the mutations identified in the HYR gene segments associated with high growth in ovo may be of great practical benefit to modify PR8 and/or wt virus gene sequences for improved growth of vaccine 'seed' viruses.
Massin, Sophie; Ventelou, Bruno; Nebout, Antoine; Verger, Pierre; Pulcini, Céline
We tested the following hypotheses: (i) risk-averse general practitioners (GPs) are more likely to be vaccinated against influenza; (ii) and risk-averse GPs recommend influenza vaccination more often to their patients. In risk-averse GPs, the perceived benefits of the vaccine and/or the perceived risks of the infectious disease might indeed outweigh the perceived risks of the vaccine. In 2010-2012, we conducted a cross-sectional survey of a nationwide French representative sample of 1136 GPs. Multivariate analyses adjusted for four stratification variables (age, gender, urban/suburban/rural practice location and annual patient consultations) and for GPs' characteristics (group/solo practice, and occasional practice of alternative medicine, e.g., homeopathy) looked for associations between their risk attitudes and self-reported vaccination behavior. Individual risk attitudes were expressed as a continuous variable, from 0 (risk-tolerant) to 10 (risk-averse). Overall, 69% of GPs reported that they were very favorable toward vaccination in general. Self-reported vaccination coverage was 78% for 2009/2010 seasonal influenza and 62% for A/H1N1 pandemic influenza. Most GPs (72%) reported recommending the pandemic influenza vaccination to at-risk young adults in 2009, but few than half (42%) to young adults not at risk. In multivariate analyses, risk-averse GPs were more often vaccinated against seasonal (marginal effect=1.3%, P=0.02) and pandemic influenza (marginal effect=1.5%, P=0.02). Risk-averse GPs recommended the pandemic influenza vaccination more often than their more risk-tolerant colleagues to patients without risk factors (marginal effect=1.7%, P=0.01), but not to their at-risk patients and were more favorable toward vaccination in general (marginal effect=1.5%, P=0.04). Individual risk attitudes may influence GPs' practices regarding influenza vaccination, both for themselves and their patients. Our results suggest that risk-averse GPs may perceive the risks
Nakayama, Misako; Ozaki, Hiroichi; Itoh, Yasushi; Soda, Kosuke; Ishigaki, Hirohito; Okamatsu, Masatoshi; Sakoda, Yoshihiro; Park, Chun-Ho; Tsuchiya, Hideaki; Kida, Hiroshi; Ogasawara, Kazumasa
H9N2 avian influenza virus causes sporadic human infection. Since humans do not possess acquired immunity specific to this virus, we examined the pathogenicity of an H9N2 virus isolated from a human and then analyzed protective effects of a vaccine in cynomolgus macaques. After intranasal challenge with A/Hong Kong/1073/1999 (H9N2) (HK1073) isolated from a human patient, viruses were isolated from nasal and tracheal swabs in unvaccinated macaques with mild fever and body weight loss. A formalin-inactivated H9N2 whole particle vaccine derived from our virus library was subcutaneously inoculated to macaques. Vaccination induced viral antigen-specific IgG and neutralization activity in sera. After intranasal challenge with H9N2, the virus was detected only the day after inoculation in the vaccinated macaques. Without vaccination, many bronchus-associated lymphoid tissues (BALTs) were formed in the lungs after infection, whereas the numbers of BALTs were smaller and the cytokine responses were weaker in the vaccinated macaques than those in the unvaccinated macaques. These findings indicate that the H9N2 avian influenza virus HK1073 is pathogenic in primates but seems to cause milder symptoms than does H7N9 influenza virus as found in our previous studies and that a formalin-inactivated H9N2 whole particle vaccine induces protective immunity against H9N2 virus. © 2016 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.
Stedman-Smith, Maggie; Kingsbury, Diana M; Dubois, Cathy L Z; Grey, Scott F
The annual costs of influenza are in the billions of dollars, with employers bearing substantial burdens. Yet, influenza vaccine uptake is sub-optimal. A random survey was administered to employees at a Midwestern public university using mixed quantitative and qualitative methods to identify the rate, characteristics, and barriers of self-reported flu vaccine uptake during March-April of 2012. The lowest uptake was among adults, ages 18 to 49 (29.8%), even though they are included in universal recommendations. Multiple regression analysis adjusted for demographic confounders showed an increase in self-identified protective hand hygiene behavior among those who reported influenza vaccine uptake compared with those who did not. Qualitative thematic analysis revealed contextual accounts of why vaccine uptake was declined including structural, perceptual, and knowledge barriers. Implementation and evaluation of novel multicomponent worksite vaccine interventions tailored to reach young and middle-aged employees including utilization of risk communication is needed to facilitate increased uptake.
Jit, Mark; Cromer, Deborah; Baguelin, Marc; Stowe, Julia; Andrews, Nick; Miller, Elizabeth
We assessed the cost-effectiveness of vaccinating pregnant women against seasonal influenza in England and Wales, taking into account the timing of vaccination relative to both the influenza season and trimester of pregnancy. Women were assumed to be vaccinated in their second or third trimester. Vaccination between September and December was found to have an incremental cost-effectiveness ratio of £23,000 per quality adjusted life year (QALY) (95% CI £10,000-£140,000) if it is assumed that infants are partially protected through their mothers, and of £28,000 per QALY gained (95% CI £13,000-£200,000) if infants are not protected. If some vaccine protection lasts for a second season, then the ratio is only £15,000 per QALY gained (95% CI £6,000-£93,000). Most of the benefit of vaccination is in preventing symptomatic episodes, regardless of health care resource use. Extending vaccination beyond December is unlikely to be cost-effective unless there is good protection into a second influenza season. Key sources of uncertainty are the cost of vaccine delivery and the quality of life detriment due to a clinically apparent episode of confirmed influenza. The cost of vaccine purchase itself is relatively low. Copyright © 2010 Elsevier Ltd. All rights reserved.
Choi, Hyo-Jick; Kim, Min-Chul; Kang, Sang-Moo; Montemagno, Carlo D
Oral influenza vaccine provides an efficient means of preventing seasonal and pandemic disease. In this work, the stability of envelope-type split influenza vaccine particles in acidic environments has been investigated. Owing to the fact that hyper-osmotic stress can significantly affect lipid assembly of vaccine, osmotic stress-induced morphological change of split vaccine particles, in conjunction with structural change of antigenic proteins, was investigated by the use of stopped-flow light scattering (SFLS), intrinsic fluorescence, transmission electron microscopy (TEM), and hemagglutination assay. Split vaccine particles were found to exhibit a step-wise morphological change in response to osmotic stress due to double-layered wall structure. The presence of hyper-osmotic stress in acidic medium (0.3 osmolarity, pH 2.0) induced a significant level of membrane perturbation as measured by SFLS and TEM, imposing more damage to antigenic proteins on vaccine envelope than can be caused by pH-induced conformational change at acidic iso-osmotic condition. Further supports were provided by the intrinsic fluorescence and hemagglutinin activity measurements. Thus, hyper-osmotic stress becomes an important factor for determining stability of split vaccine particles in acidic medium. These results are useful in better understanding the destabilizing mechanism of split influenza vaccine particles in gastric environment and in designing oral influenza vaccine formulations.
Assessing parents' knowledge and attitudes towards seasonal influenza vaccination of children before and after a seasonal influenza vaccination effectiveness study in low-income urban and rural Kenya, 2010-2011.
Oria, Prisca Adhiambo; Arunga, Geoffrey; Lebo, Emmaculate; Wong, Joshua M; Emukule, Gideon; Muthoka, Philip; Otieno, Nancy; Mutonga, David; Breiman, Robert F; Katz, Mark A
Influenza vaccine is rarely used in Kenya, and little is known about attitudes towards the vaccine. From June-September 2010, free seasonal influenza vaccine was offered to children between 6 months and 10 years old in two Population-Based Infectious Disease Surveillance (PBIDS) sites. This survey assessed attitudes about influenza, uptake of the vaccine and experiences with childhood influenza vaccination. We administered a questionnaire and held focus group discussions with parents of children of enrollment age in the two sites before and after first year of the vaccine campaign. For pre-vaccination focus group discussions, we randomly selected mothers and fathers who had an eligible child from the PBIDS database to participate. For the post-vaccination focus group discussions we stratified parents whose children were eligible for vaccination into fully vaccinated, partially vaccinated and non-vaccinated groups. Overall, 5284 and 5755 people completed pre and post-vaccination questionnaires, respectively, in Kibera and Lwak. From pre-vaccination questionnaire results, among parents who were planning on vaccinating their children, 2219 (77.6%) in Kibera and 1780 (89.6%) in Lwak said the main reason was to protect the children from seasonal influenza. In the pre-vaccination discussions, no parent had heard of the seasonal influenza vaccine. At the end of the vaccine campaign, of 18,652 eligible children, 5,817 (31.2%) were fully vaccinated, 2,073 (11.1%) were partially vaccinated and, 10,762 (57.7%) were not vaccinated. In focus group discussions, parents who declined vaccine were concerned about vaccine safety or believed seasonal influenza illness was not severe enough to warrant vaccination. Parents who declined the vaccine were mainly too busy [251(25%) in Kibera and 95 (10.5%) in Lwak], or their child was away during the vaccination period [199(19.8%) in Kibera; 94(10.4%) in Lwak]. If influenza vaccine were to be introduced more broadly in Kenya, effective
Full Text Available There is a constant threat of zoonotic influenza viruses causing a pandemic outbreak in humans. It is virtually impossible to predict which virus strain will cause the next pandemic and it takes a considerable amount of time before a safe and effective vaccine will be available once a pandemic occurs. In addition, development of pandemic vaccines is hampered by the generally poor immunogenicity of avian influenza viruses in humans. An effective pre-pandemic vaccine is therefore required as a first line of defense. Broadening of the protective efficacy of current seasonal vaccines by adding an adjuvant may be a way to provide such first line of defense. Here we evaluate whether a seasonal trivalent virosomal vaccine (TVV adjuvated with the saponin-based adjuvant Matrix-M (MM can confer protection against avian influenza H5 and H7 virus strains in mice and ferrets. We demonstrate that mice were protected from death against challenges with H5N1 and H7N7, but that the protection was not complete as evidenced by severe clinical signs. In ferrets, protection against H7N9 was not observed. In contrast, reduced upper and lower respiratory tract viral loads and reduced lung pathology, was achieved in H5N1 challenged ferrets. Together these results suggest that, at least to some extent, Matrix-M adjuvated seasonal virosomal influenza vaccine can serve as an interim measure to decrease morbidity and mortality associated with a pandemic outbreak.
La Torre, Giuseppe; Mannocci, Alice; Ursillo, Paolo; Bontempi, Claudio; Firenze, Alberto; Panico, Maria Grazia; Sferrazza, Antonella; Ronga, Chiara; D'Anna, Adele; Amodio, Emanuele; Romano, Nino; Boccia, Antonio
Italian Ministry of Health, recommends vaccination for seasonal influenza to all healthcare workers (HCW), particularly to nurses who have an important interaction with patients. The aim of this study is to conduct a systematic review in order to estimate the pooled prevalence of influenza vaccinations among nurses and ancillary workers in Italy and analyse the enhancing and hindering factors. The review was performed using 15 articles, six containing the prevalence of vaccination for nurses and ancillary workers, while the others qualitative analysis. In all the selected articles the score calculation has been carried out by using a protocol for observational studies. The nurses and ancillary workers pooled proportion of influenza vaccination was respectively 13.47% (95%CI 9.58-17.90%) and 12.52% (95%CI 9.97-15.31%). The Italian mean of influenza vaccination prevalence appear low if compared to other European countries, ranging from 15% to 29% in Countries such as UK, Germany, France. This situation of weakness should be seen as an opportunity to improve the vaccination rate for seasonal influenza significantly This should be done by intervening on the category which affirms caring less. In fact, this category has a priority to receive vaccination, due to their numbers and closer contact to patients. Research was conducted using medical database Scopus, PubMed, the search engine Google Scholar and ISI web of knowledge, and was concluded February 1st 2011.
Kim, Yeu-Chun; Lee, Su-Hwa; Choi, Won-Hyung; Choi, Hyo-Jick; Goo, Tae-Won; Lee, Ju-Hie; Quan, Fu-Shi
A painless self-immunization method with effective and broad cross-protection is urgently needed to prevent infections against newly emerging influenza viruses. In this study, we investigated the cross-protection efficacy of trivalent influenza vaccine containing inactivated A/PR/8/34 (H1N1), A/Hong Kong/68 (H3N2) and B/Lee/40 after skin vaccination using microneedle patches coated with this vaccine. Microneedle vaccination of mice in the skin provided 100% protection against lethal challenges with heterologous pandemic strain influenza A/California/04/09, heterogeneous A/Philippines/2/82 and B/Victoria/287 viruses 8 months after boost immunization. Cross-reactive serum IgG antibody responses against heterologous influenza viruses A/California/04/09, A/Philippines/2/82 and B/Victoria/287 were induced at high levels. Hemagglutination inhibition titers were also maintained at high levels against these heterogeneous viruses. Microneedle vaccination induced substantial levels of cross-reactive IgG antibody responses in the lung and cellular immune responses, as well as cross-reactive antibody-secreting plasma cells in the spleen. Viral loads in the lung were significantly (p skin vaccination with trivalent vaccine using a microneedle array could provide protection against seasonal epidemic or new pandemic strain of influenza viruses.
Lu, Peng-Jun; Srivastav, Anup; Santibanez, Tammy A; Christopher Stringer, M; Bostwick, Michael; Dever, Jill A; Stanley Kurtz, Marshica; Williams, Walter W
Since 2010, the Advisory Committee on Immunization Practices (ACIP) has recommended that all persons aged ≥6months receive annual influenza vaccination. We analyzed data from the 2015 National Internet Flu Survey (NIFS), to assess knowledge and awareness of the influenza vaccination recommendation and early influenza vaccination coverage during the 2015-16 season among adults. Predictive marginals from a multivariable logistic regression model were used to identify factors independently associated with adults' knowledge and awareness of the vaccination recommendation and early vaccine uptake during the 2015-16 influenza season. Among the 3301 respondents aged ≥18years, 19.6% indicated knowing that influenza vaccination is recommended for all persons aged ≥6months. Of respondents, 62.3% indicated awareness that there was a recommendation for influenza vaccination, but did not indicate correct knowledge of the recommended age group. Overall, 39.9% of adults aged ≥18years reported having an influenza vaccination. Age 65years and older, being female, having a college or higher education, not being in work force, having annual household income ≥$75,000, reporting having received an influenza vaccination early in the 2015-16 season, having children aged ≤17years in the household, and having high-risk conditions were independently associated with a higher correct knowledge of the influenza vaccination recommendation. Approximately 1 in 5 had correct knowledge of the recommendation that all persons aged ≥6months should receive an influenza vaccination annually, with some socio-economic groups being even less aware. Clinic based education in combination with strategies known to increase uptake of recommended vaccines, such as patient reminder/recall systems and other healthcare system-based interventions are needed to improve vaccination, which could also improve awareness. Published by Elsevier Ltd.
Full Text Available BACKGROUND: The aim of this study was to analyse the genetic patterns of Hemagglutinin (HA genes of influenza A strains circulating on Corsica Island during the 2006-2009 epidemic seasons and the 2009-2010 pandemic season. METHODS: Nasopharyngeal samples from 371 patients with influenza-like illness (ILI were collected by General Practitioners (GPs of the Sentinelles Network through a randomised selection routine. RESULTS: Phylogenetic analysis of HA revealed that A/H3N2 strains circulating on Corsica were closely related to the WHO recommended vaccine strains in each analyzed season (2006-2007 to 2008-2009. Seasonal Corsican influenza A/H1N1 isolated during the 2007-2008 season had drifted towards the A/Brisbane/59/2007 lineage, the A/H1N1 vaccine strain for the 2008-2009 season. The A/H1N1 2009 (A/H1N1pdm strains isolated on Corsica Island were characterized by the S220T mutation specific to clade 7 isolates. It should be noted that Corsican isolates formed a separate sub-clade of clade 7 as a consequence of the presence of the fixed substitution D222E. The percentages of the perfect match vaccine efficacy, estimated by using the p(epitope model, against influenza viruses circulating on Corsica Island varied substantially across the four seasons analyzed, and tend to be highest for A/H1N1 compared with A/H3N2 vaccines, suggesting that cross-immunity seems to be stronger for the H1 HA gene. CONCLUSION: The molecular analysis of the HA gene of influenza viruses that circulated on Corsica Island between 2006-2010 showed for each season the presence of a dominant lineage characterized by at least one fixed mutation. The A/H3N2 and A/H1N1pdm isolates were characterized by multiples fixation at antigenic sites. The fixation of specific mutations at each outbreak could be explained by the combination of a neutral phenomenon and a founder effect, favoring the presence of a dominant lineage in a closed environment such as Corsica Island.
Full Text Available Abstract Background In most countries the coverage of seasonal influenza vaccination in pregnant women is low. We investigated the acceptance, reasons for rejection and professional involvement related to vaccine information in pregnant women in Valencia, Spain. Methods Observational retrospective study in 200 pregnant women, 100 vaccinated and 100 unvaccinated, were interviewed during the 2014/2015 vaccination campaign. Electronic medical records, immunization registry and telephone interviews were used to determine reasons for vaccination and immunization rejection. Results 40.5% of pregnant women in the health department were vaccinated. The midwife was identified as source of information for 89% of women. The vaccine was rejected due to low perceptions of risk of influenza infection (23%, lack of information (19%, considering the vaccine as superfluous (16%, close proximity of delivery date (13% and fear of side effects (12%. Conclusion Pregnant women in Spain declined to be vaccinated due to under-estimation of the risk of contracting or being harmed by influenza, and lack of information. Interventions aiming to optimize vaccination coverage should include information addressing the safety and effectiveness of the current vaccine together with improved professional training and motivation.
Full Text Available Abstract The Global Influenza Hospital Surveillance Network (GIHSN has established a prospective, active surveillance, hospital-based epidemiological study to collect epidemiological and virological data for the Northern and Southern Hemispheres over several consecutive seasons. It focuses exclusively on severe cases of influenza requiring hospitalization. A standard protocol is shared between sites allowing comparison and pooling of results. During the 2014–2015 influenza season, the GIHSN included seven coordinating sites from six countries (St. Petersburg and Moscow, Russian Federation; Prague, Czech Republic; Istanbul, Turkey; Beijing, China; Valencia, Spain; and Rio de Janeiro, Brazil. Here, we present the detailed epidemiological and influenza vaccine effectiveness findings for the Northern Hemisphere 2014–2015 influenza season.
Germain J P Fernando
Full Text Available BACKGROUND: Over 14 million people die each year from infectious diseases despite extensive vaccine use . The needle and syringe--first invented in 1853--is still the primary delivery device, injecting liquid vaccine into muscle. Vaccines could be far more effective if they were precisely delivered into the narrow layer just beneath the skin surface that contains a much higher density of potent antigen-presenting cells (APCs essential to generate a protective immune response. We hypothesized that successful vaccination could be achieved this way with far lower antigen doses than required by the needle and syringe. METHODOLOGY/PRINCIPAL FINDINGS: To meet this objective, using a probability-based theoretical analysis for targeting skin APCs, we designed the Nanopatch, which contains an array of densely packed projections (21025/cm(2 invisible to the human eye (110 microm in length, tapering to tips with a sharpness of <1000 nm, that are dry-coated with vaccine and applied to the skin for two minutes. Here we show that the Nanopatches deliver a seasonal influenza vaccine (Fluvax 2008 to directly contact thousands of APCs, in excellent agreement with theoretical prediction. By physically targeting vaccine directly to these cells we induced protective levels of functional antibody responses in mice and also protection against an influenza virus challenge that are comparable to the vaccine delivered intramuscularly with the needle and syringe--but with less than 1/100(th of the delivered antigen. CONCLUSIONS/SIGNIFICANCE: Our results represent a marked improvement--an order of magnitude greater than reported by others--for injected doses administered by other delivery methods, without reliance on an added adjuvant, and with only a single vaccination. This study provides a proven mathematical/engineering delivery device template for extension into human studies--and we speculate that successful translation of these findings into humans could
Orenstein, Walter A; Schaffner, William
The Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention (CDC) has been increasing the size of the population for whom influenza vaccine is recommended to reduce the substantial and persistent annual health burden of influenza. Realization of current and future public health influenza immunization goals requires assuring vaccine supply will be adequate to meet demand. This has posed distinct challenges for the many stakeholders in the influenza vaccine program--government agencies, federal, state, and local policymakers, vaccine manufacturers and distributors, and the medical community--each of whom must make critical decisions in a constantly shifting environment. Factors such as the yearly changes in influenza virus strains, the complicated vaccine production and distribution process, revisions in vaccination recommendations, and changing demographics can all affect the delicate balance between supply and demand. While vaccine shortages and delays have been well-publicized concerns in the recent past, there has been a marked increase in supply in the past several years, with substantial growth in supply expected in the future. The primary issue today is to strengthen the demand for the influenza vaccine, which would in turn help ensure the continued availability of the vaccine to reduce disease burden. A number of strategies are discussed, including increased efforts to publicize and fully implement current CDC recommendations and to offer influenza vaccine beyond the typical vaccination season of October and November, because in the great majority of years, vaccination into January and beyond will still provide health benefits.
El-Zoghby Elham F
Full Text Available Abstract Background Uninterrupted transmission of highly pathogenic avian influenza virus (HPAIV H5N1 of clade 2.2.1 in Egypt since 2006 resulted in establishment of two main genetic clusters. The 2.2.1/C group where all recent human and majority of backyard origin viruses clustered together, meanwhile the majority of viruses derived from vaccinated poultry in commercial farms grouped in 126.96.36.199 clade. Findings In the present investigation, an HPAIV H5N1 was isolated from twenty weeks old layers chickens that were vaccinated with a homologous H5N1 vaccine at 1, 7 and 16 weeks old. At twenty weeks of age, birds showed cyanosis of comb and wattle, decrease in egg production and up to 27% mortality. Examined serum samples showed low antibody titer in HI test (Log2 3.2± 4.2. The hemagglutinin (HA and neuraminidase (NA genes of the isolated virus were closely related to viruses in 2.2.1/C group isolated from poultry in live bird market (LBM and backyards or from infected people. Conspicuous mutations in the HA and NA genes including a deletion within the receptor binding domain in the HA globular head region were observed. Conclusions Despite repeated vaccination of layer chickens using a homologous H5N1 vaccine, infection with HPAIV H5N1 resulted in significant morbidity and mortality. In endemic countries like Egypt, rigorous control measures including enforcement of biosecurity, culling of infected birds and constant update of vaccine virus strains are highly required to prevent circulation of HPAIV H5N1 between backyard birds, commercial poultry, LBM and humans.