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.

Cell-Mediated Immunity Against Antigenically Drifted Influenza A(H3N2) Viruses in Children During a Vaccine Mismatch Season

“…In young and adolescent children aged 3-17 years, IIV elicited cross-reactive Ab responses, but at 10-fold lower levels than vaccine-specific Ab responses [13]. In the same group of study participants, the current study found that, in contrast to the Ab responses, IIV elicited significant cross-reactive PB responses, MBC induction, and Tcell responses against the drifted strain.…”

“…The study design, recruitment, enrollment criteria, and vaccination status of the children have been recently reported [13]. The study participants were generally healthy.…”

“…Virus propagation and titration were performed as previously described [13]. To assess virus-specific B-cell and T-cell responses, wild-type A/Texas/50/2012 (H3N2) (Tex/50) virus was used as vaccine strain, and A/Nebraska/04/2014 (H3N2) (Neb/04) was used as a representative drifted strain.…”

“…As a result, vaccine effectiveness (VE) against antigenically drifted A(H3N2) strains was significantly reduced as compared to the vaccine A(H3N2) strain [11,12]. The serological study of children aged 3-17 years found that cross-reactive Ab responses against drifted A(H3N2) strains following IIV receipt were significantly lower than vaccine-specific responses during the 2014-2015 season [13]. The current study examined the cross-reactivity of both B and T cells among IIV recipients against A(H3N2) viruses.…”

Differential gene expression elicited by children in response to the 2015–16 live attenuated versus inactivated influenza vaccine

“…In a previous study of children ages 3 to 17 years, post 2014–2015 influenza vaccination antibody titers were significantly higher in response to IIV than to LAIV [8]. Moreover, microneutralization antibodies measuring cross-reactive protection against influenza were significantly higher among recipients of IIV than LAIV.…”