Repeated annual influenza vaccination and vaccine effectiveness: review of evidence

<p><b>Introduction</b>: 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.</p> <p><b>Areas covered</b>: 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.</p> <p><b>Expert commentary</b>: 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.</p

Proportion of unvaccinated students in each group sample by country of birth (Canada /outside Canada).

<p>Proportion of unvaccinated students in each group sample by country of birth (Canada /outside Canada).</p

Prevalence of risk factors for acquiring measles during the 2011 outbreak in Quebec and impact of the province-wide school-based vaccination campaign on population immunity

<div><p>Background</p><p>A large measles outbreak occurred in Quebec, Canada, in 2011. Although nearly two-thirds of the cases occurred in only two health districts, a mass vaccination campaign targeting all Quebec elementary and high school students without valid two-dose history was undertaken to prevent future outbreaks. We compared rates of non-vaccination and age at first measles vaccine dose among students in the two most-affected districts and the rest of the province and estimated the improvement in overall student measles immunity due to the mass school-based vaccination campaign.</p><p>Methods</p><p>Data were extracted from the provincial vaccination registry for students in kindergarten to grade 11 during the 2011/2012 school year. A telephone survey was conducted in three sub-groups: students whose first measles vaccine dose recorded in the vaccination registry was received during the 2011 school vaccination campaign; students with no dose recorded in the registry whose parents refused receipt during the school campaign; and students with no dose recorded in the registry and no information about parental consent/refusal during the school campaign.</p><p>Results</p><p>Neither the prevalence of being non-vaccinated nor a younger age at first pediatric dose were higher in the two most-affected districts versus the rest of the province. The school campaign vaccinated nearly 8% of all students including 7% who previously received at least one dose. Before the outbreak, 3% of students were not vaccinated and one-third of these (1%/3%) were vaccinated during the campaign. The campaign likely increased the absolute school population immunity by just 1.7%.</p><p>Conclusion</p><p>The concentration of measles cases in the two most-affected health districts during the large Quebec outbreak is not explained by more students who were unvaccinated or who had received their first vaccine dose at a younger age. The vaccination campaign reached one-third of unvaccinated students and only marginally improved population immunity.</p></div

Absolute increase in the school population immunity following the mass campaign by vaccination status before the campaign.

<p>Absolute increase in the school population immunity following the mass campaign by vaccination status before the campaign.</p

Measles vaccine coverage before the outbreak in May 2011 and after the mass vaccination campaign in September 2013 and number of students vaccinated during the outbreak and during and after the vaccination campaign.

<p>Measles vaccine coverage before the outbreak in May 2011 and after the mass vaccination campaign in September 2013 and number of students vaccinated during the outbreak and during and after the vaccination campaign.</p

Participation in the telephone survey and proportion of unvaccinated students per subgroup and in the student population.

<p>Participation in the telephone survey and proportion of unvaccinated students per subgroup and in the student population.</p

Age at first dose of measles vaccine and vaccine coverage among elementary students, high school students and the whole student population according to the geographic area of residence in May 2011, before the outbreak.

<p>Age at first dose of measles vaccine and vaccine coverage among elementary students, high school students and the whole student population according to the geographic area of residence in May 2011, before the outbreak.</p

Cross-strain influenza A(H1N1) antibody responses measured by HI assay.^*

<p>HI  =  hemagglutination inhibition; TIV  =  trivalent inactivated influenza vaccine. Note that undetectable titres <10 were assigned a value of 5.</p>*<p>Unit of analysis pooled sera from 5 mice, thus 10 pools from 50 mice were available for this experiment.</p>a<p>Measured two weeks after specified TIV dose;</p>b<p>Measured two months after specified TIV dose.</p>†<p>Compared to pre-immunization for initiating antigens; compared to immediately preceding titre for boosting antigens.</p><p>Brisbane  =  A/Brisbane/59/2007(H1N1)-like, component of the northern hemisphere 2008–09 and 2009–10 TIV.</p><p>California  =  A/California/07/2009(H1N1)-like, component of the northern hemisphere 2010–11 TIV.</p

Specimen inclusion/exclusion criteria for primary vaccine effectiveness analysis.

<p>¹Patients whom nurses were not able to approach because of early discharge or other operational considerations (i.e. workload demands during peak weeks of respiratory admissions); ²Symptoms onset >72h after hospital admission; ³Exclusions are not mutually exclusive; ⁴15 respiratory syncytial viruses, 13 entero/rhinoviruses, 6 parainfluenza viruses, 2 coronaviruses, 1 human metapneumovirus</p

Cross-strain influenza A(H3N2) antibody responses measured by HI assay.^*

<p>HI = hemagglutination inhibition; TIV  =  trivalent inactivated influenza vaccine. Note that undetectable titres <10 were assigned a value of 5.</p>*<p>Unit of analysis pooled sera from 5 mice, thus 10 pools from 50 mice were available for this experiment.</p>a<p>Measured two weeks after specified TIV dose;</p>b<p>Measured two months after specified TIV dose.</p>†<p>Compared to pre-immunization for priming antigens; compared to immediately preceding titre for boosting antigens.</p><p>Brisbane-like  =  A/Uruguay/716/2007(NYMC 175C)(H3N2) considered antigenically equivalent to the WHO recommended A/Brisbane/10/2007(H3N2) component of the 2008–09 northern hemisphere TIV.</p><p>Perth  =  A/Perth/16/2009(H3N2)-like, component of the northern hemisphere 2010–11 TIV.</p