Abstract

Human influenza A(H3N2) viruses that predominated during the moderately severe 2014-2015 influenza season differed antigenically from the vaccine component, resulting in reduced vaccine effectiveness (VE). To examine antibody responses to 2014-2015 inactivated influenza vaccine (IIV) and live-attenuated influenza vaccine (LAIV) among children and adolescents, we collected sera before and after vaccination from 150 children aged 3 to 17 years enrolled at health care facilities. Hemagglutination inhibition (HI) assays were used to assess the antibody responses to vaccine strains. We evaluated cross-reactive antibody responses against two representative A(H3N2) viruses that had antigenically drifted from the A(H3N2) vaccine component using microneutralization (MN) assays. Postvaccination antibody titers to drifted A(H3N2) viruses were higher following receipt of IIV (MN geometric mean titers [GMTs], 63 to 68; 38 to 45% achieved seroconversion) versus LAIV (MN GMT, 22; only 3 to 5% achieved seroconversion). In 9- to 17-year-olds, the highest MN titers were observed among IIV-vaccinated individuals who had received LAIV in the previous season. Among all IIV recipients aged 3 to 17 years, the strongest predictor of antibody responses to the drifted viruses was the prevaccination titers to the vaccine strain. The results of our study suggest that in an antigenically drifted influenza season, vaccination still induced cross-reactive antibody responses to drifted circulating A(H3N2) viruses, although higher antibody titers may be required for protection. Antibody responses to drifted A(H3N2) viruses following vaccination were influenced by multiple factors, including vaccine type and preexisting immunity from prior exposure.

Highlights

  • Neutralizing antibodies against hemagglutinin (HA) on the surfaces of influenza viruses have been considered the major immune mechanism that provides protection against influenza infection [1, 2]

  • There was no statistical difference in the characteristics of those who received live-attenuated influenza vaccine (LAIV) versus those who received inactivated influenza vaccine (IIV) when comparing age, sex, and the interval between paired serum sample collections (P Ͼ 0.05)

  • Influenza Vaccine Responses in an A(H3N2) Drifted Year study, the majority of subjects had preexisting Hemagglutination inhibition (HI) antibodies to vaccine viruses: HI Geometric mean titers (GMTs) antibody titers among both IIV and LAIV recipients were 60 to influenza A(H1N1), 119 to A(H3N2), 72 to B/Yamagata, and 35 to B/Victoria vaccine components and were not statistically different between IIV and LAIV recipients (Table 2)

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Summary

Introduction

Neutralizing antibodies against hemagglutinin (HA) on the surfaces of influenza viruses have been considered the major immune mechanism that provides protection against influenza infection [1, 2]. In the 2014-2015 influenza season, new clusters of A(H3N2) viruses became predominant [10,11,12,13] and were characterized into two genetic groups based on HA sequences: 3C.2a and 3C.3a [14, 15]. Even when seasonal influenza vaccines are antigenically mismatched to circulating influenza viruses, vaccination may still provide partial protection by inducing cross-reactive antibody responses to circulating strains through shared epitopes on HA or other viral proteins [19]. We measured serum antibody responses to 2014-2015 live-attenuated and inactivated influenza vaccines, evaluated the levels of neutralizing antibodies to antigenically drifted influenza A(H3N2) strains, and explored factors that may influence cross-reactive antibody responses to drifted A(H3N2) viruses following vaccination

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