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

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

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

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

Effective reproduction number (<i>R_eff</i>) according to various scenarios of population immunity by initial basic reproduction number (<i>R₀</i>) assumed.

<p><b>SPR</b> = Sero-protection rate – defined as the proportion (%) considered sero-protected on the basis of having met or exceeded the specified antibody titre threshold; <b>pre-H1N1pdm09:</b> 2009 H1N1 pandemic virus; SPR presented based on PRE-pandemic antibody levels measured in 2009 or earlier; <b>post-H1N1pdm09:</b> 2009 H1N1 pandemic virus; SPR presented based on POST-pandemic antibody levels measured in fall 2010; <b>H3N2v:</b> swine-origin H3N2 variant strain; SPR presented based on antibody levels measured in sera collected in fall 2010; <b>post-Brisbane:</b> a contemporary seasonal human influenza H3N2 virus; SPR presented based post-circulation antibody levels in sera collected in fall 2010; <b>SPR40:</b> the proportion considered sero-protected according to the standard hemagglutination inhibition (HI) titre threshold of 40; <b>½SPR40:</b> assumes half the individuals meeting SPR40 are considered sero-protected; <b>SPR80:</b> the proportion considered sero-protected according to a hemagglutination inhibition (HI) titre threshold of 80.</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

Main input parameter values for Greater Vancouver Area (GVA) contact network model.

<p>HI = hemagglutination inhibition assay; SPR = Sero-protection rate – defined as the proportion (%) considered sero-protected on the basis of having met or exceeded the specified antibody titre threshold.</p><p><b>pre-H1N1pdm09</b>: 2009 H1N1 pandemic virus; SPR based on PRE-pandemic antibody levels in 2009 or earlier.</p><p><b>post-H1N1pdm09</b>: 2009 H1N1 pandemic virus; SPR based on POST-pandemic antibody levels fall 2010.</p><p><b>H3N2v:</b> swine-origin H3N2 variant strain; SPR based on antibody levels in fall 2010.</p><p><b>post-Brisbane</b>: a seasonal human influenza H3N2 virus; SPR based on antibody levels fall 2010.</p>a<p>Statistics Canada 2006 Community Profiles [<a href="http://www12.statcan.ca/census-recensement/2006/dp-pd/prof/92-591/index.cfm?Lang=E" target="_blank">http://www12.statcan.ca/census-recensement/2006/dp-pd/prof/92-591/index.cfm?Lang=E</a>].</p>b<p>The same typical seasonal influenza parameter values were applied to each of the three influenza viruses assessed, recognizing their human influenza virus ancestral origins.</p>c<p>Based on 100% SPR defined at HI titre ≥40; ^dBased on 50%SPR defined at HI titre ≥40; ^e100%SPR defined at HI titre ≥80.</p><p>Note that a blended composite of sero-protection based on a gradient of immunity defined as <b>¼</b>SPR20, ½SPR40, ¾SPR80 and 100% SPR160 was also explored (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0054015#pone.0054015.s003" target="_blank">Table S1</a> and narrative).</p

Age-stratified epidemic attack rates by scenario and assumed basic reproduction number (<i>R₀</i> = 1.40). SPR

<p> = Sero-protection rate – defined as the proportion (%) considered sero-protected on the basis of having met or exceeded the specified antibody titre threshold; <b>pre-H1N1pdm09:</b> 2009 H1N1 pandemic virus; SPR presented based on PRE-pandemic antibody levels measured in 2009 or earlier; <b>post-H1N1pdm09:</b> 2009 H1N1 pandemic virus; SPR presented based on POST-pandemic antibody levels measured in fall 2010; <b>H3N2v:</b> swine-origin H3N2 variant strain; SPR presented based on antibody levels measured in sera collected in fall 2010; <b>post-Brisbane:</b> a contemporary seasonal human influenza H3N2 virus; SPR presented based post-circulation antibody levels in sera collected in fall 2010; <b>SPR40:</b> the proportion considered sero-protected according to the standard hemagglutination inhibition (HI) titre threshold of 40; <b>½SPR40:</b> assumes half the individuals meeting SPR40 are considered sero-protected; <b>SPR80:</b> the proportion considered sero-protected according to a hemagglutination inhibition (HI) titre threshold of 80 Overall attack rates are indicated by the horizontal line. Based on simulations using age-specific parameters, these overall attack rates were derived as the total number of infections divided by the total population size.</p