Influenza vaccine effectiveness in households with children during the 2012-2013 season: assessments of prior vaccination and serologic susceptibility

Abstract

Background: There are recognized needs to identify determinants of influenza vaccine effectiveness (VE), including the effect of repeated annual vaccination.

Methods: We recruited 321 households with 1426 members, including 833 children, and followed them during the 2012-2013 influenza season; specimens were collected from subjects with reported acute respiratory illnesses. We estimated the effectiveness of documented influenza vaccination in preventing laboratory-confirmed influenza, using adjusted Cox proportional hazards models. Antibody titers in a subset of subjects were determined by a hemagglutination inhibition assay to determine the subjects' preseason susceptibility to influenza.

Results: Influenza was identified in 76 (24%) households and 111 (8%) individuals. VE point estimates indicated significant protection in adults (48%; 95% confidence interval [CI], 1%-72%), similar protection in children aged 9-17 years (49%; 95% CI, -16% to 78%), but no evidence of effectiveness in children aged <9 years (-4%; 95% CI, -110% to 49%). Lower VE was observed in those vaccinated in both the current and prior seasons, compared with those vaccinated in the current season only; susceptibility titers against type A but not type B were consistent with this observation. Residual protection from vaccination in the prior season was indicated by both VE and serologic results.

Conclusions: Prior vaccination appears to modify VE by both residual protection and reduced vaccine response.

Keywords: households with children; influenza; serologic susceptibility; vaccine effectiveness.

Figure 1.

Preseason susceptibility, based on antibody titers measured by hemagglutination inhibition (HAI) and neuraminidase inhibition (NAI) assays, in subjects, by combinations of influenza vaccination status in the 2011–2012 and 2012–2013 seasons. ^aAntibody titers measured by HAI and NAI assays in sera collected from a subset of subjects aged ≥13 years at preseason visits (or at enrollment, for subjects without preseason specimens and no evidence of influenza vaccine receipt) were used to estimate preseason susceptibility to influenza; ^bSera were tested with the HAI assay, using as antigens the virus strains present in the 2012–2013 North American influenza vaccine (A[H1N1]: A/California/07/2009; A[H3N2]: A/Texas/50/2012 [A/Victoria/361/2011-like]; B/Yamagata: B/Texas/20/2011 [B/Wisconsin/1/2010-like]) plus the alternative influenza B lineage not contained in the vaccine (B Victoria: B/Brisbane/60/2008); ^cSera were tested with the NAI assay, using the influenza A(H3N2) strain present in the 2012–2013 North American influenza vaccine (A/Texas/50/2012 [A/Victoria/361/2011-like]) as the antigen; ^dEach circle indicates the titer of an individual observation. Linked lines indicate the geometric mean titer (GMT) ± the geometric standard deviation; ^eAll vaccination groups (both years, current only, and prior only) had significantly higher GMTs (P < .001) than those unvaccinated both years for all antigens; ^fGMTs were significantly higher (P = .03) among those vaccinated in the current year only, compared with those vaccinated both years for the H3 antigen but not for the other antigens.

Figure 2.

Preseason susceptibility, based on antibody titers measured by hemagglutination inhibition (HAI) and neuraminidase inhibition (NAI) assays, in subjects, by influenza vaccination and infection status. ^aAntibody titers measured by HAI and NAI assays in sera collected from a subset of subjects aged ≥13 years at preseason visits (or at enrollment, for subjects without preseason specimens and no evidence of influenza vaccine receipt) were used to estimate preseason susceptibility to influenza; ^bSera were tested with the HAI assay, using as antigens the virus strains present in the 2012–2013 North American influenza vaccine (A[H1N1]: A/California/07/2009; A[H3N2]: A/Texas/50/2012 [A/Victoria/361/2011-like]; B/Yamagata: B/Texas/20/2011 [B/Wisconsin/1/2010-like]) plus the alternative influenza B lineage not contained in the vaccine (B Victoria: B/Brisbane/60/2008); ^cSera were tested with the NAI assay, using the influenza A(H3N2) strain present in the 2012–2013 North American influenza vaccine (A/Texas/50/2012 [A/Victoria/361/2011-like]) as the antigen; ^dEach circle indicates the titer of an individual observation. Linked lines indicate the geometric mean titer ± the geometric standard deviation; ^eInfluenza A(H3N2) cases had significantly lower geometric mean HAI and NAI titers than noncases overall (P = .02 and P = .02, respectively); this pattern was consistent for both vaccinated subjects (P = .06 and P = .09, respectively) and unvaccinated subjects (P = .17 and P = .07, respectively); ^fInfluenza B/Yamagata cases had significantly lower geometric mean HAI titers than noncases overall (P = .01); this pattern was consistent for both vaccinated subjects (P = .13) and unvaccinated subjects (P = .11).