Influenza Vaccine Effectiveness in the Community and the Household

Ohmit, Suzanne E.; Petrie, Joshua G.; Malosh, Ryan E.; Cowling, Benjamin J.; Thompson, Mark G.; Shay, David K.; Monto, Arnold S.

doi:10.1093/cid/cit060

Cited by 173 publications

(179 citation statements)

References 23 publications

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“…There was renewed interest in this topic after the test-negative design was first used to estimate vaccine effectiveness for preventing laboratory-confirmed influenza during the [2004][2005] season [3]. After the 2009 pandemic, investigators in Canada and the US separately reported the effects of repeated vaccination during the 2010-2011 season [4,5]. Since then, multiple studies have assessed the effect of repeated vaccination.…”

Section: Introductionmentioning

confidence: 99%

Repeated annual influenza vaccination and vaccine effectiveness: review of evidence

Belongia

Skowronski

McLean

et al. 2017

Expert Review of Vaccines

221

185

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Introduction: Studies in the 1970s and 1980s signaled concern that repeated influenza vaccination could affect vaccine protection. The antigenic distance hypothesis provided a theoretical framework to explain variability in repeat vaccination effects based on antigenic similarity between successive vaccine components and the epidemic strain. Areas covered: A meta-analysis of vaccine effectiveness studies from 2010-11 through 2014-15 shows substantial heterogeneity in repeat vaccination effects within and between seasons and subtypes. When negative effects were observed, they were most pronounced for H3N2, especially in 2014-15 when vaccine components were unchanged and antigenically distinct from the epidemic strain. Studies of repeated vaccination across multiple seasons suggest that vaccine effectiveness may be influenced by more than one prior season. In immunogenicity studies, repeated vaccination blunts the hemagglutinin antibody response, particularly for H3N2. Expert commentary: Substantial heterogeneity in repeated vaccination effects is not surprising given the variation in study populations and seasons, and the variable effects of antigenic distance and immunological landscape in different age groups and populations. Caution is required in the interpretation of pooled results across multiple seasons, since this can mask important variation in repeat vaccination effects between seasons. Multi-season clinical studies are needed to understand repeat vaccination effects and guide recommendations. ARTICLE HISTORY

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Section: Introductionmentioning

confidence: 99%

Repeated annual influenza vaccination and vaccine effectiveness: review of evidence

Belongia

Skowronski

McLean

et al. 2017

Expert Review of Vaccines

221

185

View full text Add to dashboard Cite

show abstract

“…Pandemic viruses spread more rapidly and cause more severe disease than epidemic strains, as observed for the 1918 Spanish influenza, the 1957 Asian influenza, the 1968 Hong Kong influenza, and the 2009 swine origin influenza (4) viruses. Vaccination is the most effective means of limiting the spread of influenza viruses; however, the vaccine strain must be closely matched to the circulating strain, and efficacy varies from year to year (1,5,6). Current vaccines rely on the induction of neutralizing antibodies targeting the globular head of the viral hemagglutinin (HA) (7).…”

mentioning

confidence: 99%

“…nfluenza A and B viruses remain a substantial public health burden, with seasonal epidemics resulting in significant morbidity, mortality, and economic loss (1)(2)(3). Pandemic outbreaks occur when antigenically novel influenza A viruses emerge in a population with little preexisting immunity (4).…”

mentioning

confidence: 99%

Synthetic Toll-Like Receptor 4 (TLR4) and TLR7 Ligands as Influenza Virus Vaccine Adjuvants Induce Rapid, Sustained, and Broadly Protective Responses

Goff

Hayashi

Martínez-Gil

et al. 2015

J Virol

105

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Current vaccines against influenza virus infection rely on the induction of neutralizing antibodies targeting the globular head of the viral hemagglutinin (HA). Protection against seasonal antigenic drift or sporadic pandemic outbreaks requires further vaccine development to induce cross-protective humoral responses, potentially to the more conserved HA stalk region. Here, we present a novel viral vaccine adjuvant comprised of two synthetic ligands for Toll-like receptor 4 (TLR4) and TLR7. 1Z105 is a substituted pyrimido[5,4-b]indole specific for the TLR4-MD2 complex, and 1V270 is a phospholipid-conjugated TLR7 agonist. Separately, 1Z105 induces rapid Th2-associated IgG1 responses, and 1V270 potently generates Th1 cellular immunity. 1Z105 and 1V270 in combination with recombinant HA from the A/Puerto Rico/8/1934 strain (rPR/8 HA) effectively induces rapid and sustained humoral immunity that is protective against lethal challenge with a homologous virus. More importantly, immunization with the combined adjuvant and rPR/8 HA, a commercially available split vaccine, or chimeric rHA antigens significantly improves protection against both heterologous and heterosubtypic challenge viruses. Heterosubtypic protection is associated with broadly reactive antibodies to HA stalk epitopes. Histological examination and cytokine profiling reveal that intramuscular (i.m.) administration of 1Z105 and 1V270 is less reactogenic than a squalene-based adjuvant, AddaVax. In summary, the combination of 1Z105 and 1V270 with a recombinant HA induces rapid, long-lasting, and balanced Th1-and Th2-type immunity; demonstrates efficacy in a variety of murine influenza virus vaccine models assaying homologous, heterologous, and heterosubtypic challenge viruses; and has an excellent safety profile. IMPORTANCENovel adjuvants are needed to enhance immunogenicity and increase the protective breadth of influenza virus vaccines to reduce the seasonal disease burden and ensure pandemic preparedness. We show here that the combination of synthetic Toll-like receptor 4 (TLR4) and TLR7 ligands is a potent adjuvant for recombinant influenza virus hemagglutinin, inducing rapid and sustained immunity that is protective against influenza viruses in homologous, heterologous, and heterosubtypic challenge models. Combining TLR4 and TLR7 ligands balances Th1-and Th2-type immune responses for long-lived cellular and neutralizing humoral immunity against the viral hemagglutinin. The combined adjuvant has an attractive safety profile and the potential to augment seasonal-vaccine breadth, contribute to a broadly neutralizing universal vaccine formulation, and improve response time in an emerging pandemic. Influenza A and B viruses remain a substantial public health burden, with seasonal epidemics resulting in significant morbidity, mortality, and economic loss (1-3). Pandemic outbreaks occur when antigenically novel influenza A viruses emerge in a population with little preexisting immunity (4). Pandemic viruses spread more rapidly and cause more severe di...

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“…Low vaccine efficacy was also observed in the elderly during the 2012-2013 epidemic (caused mostly by H3N2 strains) (8). Furthermore, mismatch-independent vaccine failure in certain populations (9) and the pandemic threat from avian viruses like H7N9 and other zoonotic influenza viruses (10)(11)(12) warrant the development of better, longer-lasting, and broader vaccines.…”

mentioning

confidence: 99%

Hemagglutinin Stalk-Based Universal Vaccine Constructs Protect against Group 2 Influenza A Viruses

Margine

Krammer

Hai

et al. 2013

J Virol

183

161

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f Current influenza virus vaccines contain H1N1 (phylogenetic group 1 hemagglutinin), H3N2 (phylogenetic group 2 hemagglutinin), and influenza B virus components. These vaccines induce good protection against closely matched strains by predominantly eliciting antibodies against the membrane distal globular head domain of their respective viral hemagglutinins. This domain, however, undergoes rapid antigenic drift, allowing the virus to escape neutralizing antibody responses. The membrane proximal stalk domain of the hemagglutinin is much more conserved compared to the head domain. In recent years, a growing collection of antibodies that neutralize a broad range of influenza virus strains and subtypes by binding to this domain has been isolated. Here, we demonstrate that a vaccination strategy based on the stalk domain of the H3 hemagglutinin (group 2) induces in mice broadly neutralizing anti-stalk antibodies that are highly cross-reactive to heterologous H3, H10, H14, H15, and H7 (derived from the novel Chinese H7N9 virus) hemagglutinins. Furthermore, we demonstrate that these antibodies confer broad protection against influenza viruses expressing various group 2 hemagglutinins, including an H7 subtype. Through passive transfer experiments, we show that the protection is mediated mainly by neutralizing antibodies against the stalk domain. Our data suggest that, in mice, a vaccine strategy based on the hemagglutinin stalk domain can protect against viruses expressing divergent group 2 hemagglutinins.

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Influenza Vaccine Effectiveness in the Community and the Household

Abstract: Vaccine effectiveness estimates were lower than those demonstrated in other observational studies carried out during the same season. The unexpected findings of lower effectiveness with repeated vaccination and no protection given household exposure require further study.

Cited by 173 publications

References 23 publications

Repeated annual influenza vaccination and vaccine effectiveness: review of evidence

Repeated annual influenza vaccination and vaccine effectiveness: review of evidence

Synthetic Toll-Like Receptor 4 (TLR4) and TLR7 Ligands as Influenza Virus Vaccine Adjuvants Induce Rapid, Sustained, and Broadly Protective Responses

Hemagglutinin Stalk-Based Universal Vaccine Constructs Protect against Group 2 Influenza A Viruses

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