Neutralizing Antibody Responses to Antigenically Drifted Influenza A(H3N2) Viruses among Children and Adolescents following 2014-2015 Inactivated and Live Attenuated Influenza Vaccination

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.

FIG 1

Microneutralization (MN) titers pre- and postvaccination in the 2014-2015 influenza season stratified by age groups and prior season vaccination history. Pre- and postvaccination MN titers were graphed as geometric mean titers (GMTs) with 95% confidence intervals (95% CI). MN antibody responses were stratified by age groups 3- to 8-year-olds (A) and 9- to 17-year-olds (B) and vaccination history from the 2013-2014 and 2014-2015 seasons. MN titer distributions to vaccine virus A/Texas/50/2012 (Tx50) and drifted A(H3N2) viruses A/Switzerland/9715293/2013 (SW9715293), A/Nebraska/04/2014 (NE04) following 2014-2015 IIV and LAIV are shown. No vax, no vaccination.

FIG 2

Microneutralization (MN) titer distributions to A(H3N2) vaccine and drifted viruses postvaccination with 2014-2015 IIV and LAIV. MN titer distributions to vaccine virus A/Texas/50/2012 (TX50) and drifted A(H3N2) viruses A/Switzerland/9715293/2013 (SW9715293), A/Nebraska/04/2014 (NE04) following 2014-2015 IIV and LAIV are shown.