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

Background. Emergence of antigenically drifted influenza A(H3N2) viruses resulted in reduced vaccine effectiveness in all age groups during the 2014-2015 influenza season. In children, inactivated influenza vaccine (IIV) elicited neutralizing antibodies (Abs) against drifted strains at significantly lower levels than against the vaccine strain. Little is known about the cross-reactivity of cellmediated immunity against drifted strains in children. Methods. Children aged 3-17 years (n = 48) received IIV during the 2014-2015 influenza season. Peripheral blood mononudear cells, collected before (on day 0) and after (on days 7 and 21) vaccination were evaluated for induction of cross-reactive plasmablasts, memory cells, and cytokine-secreting CD4⁺ and CD8⁺ T cells against the vaccine and drifted A(H3N2) viruses by an enzymelinked immunospot assay and flow cytometry. Results. IIV increased frequencies of plasmablasts and memory B cells. The overall induction of the T-cell response was not significant. Both B-cell and T-cell responses showed significant cross-reactivity against A(H3N2) viruses. Age and preexisting immunity affected virus-specific plasmablast responses and fold-change of T-cell responses, respectively. The proportion of T-helper type 1-prone (ie, interferon γ-or tumor necrosis factor α-secreting) CD4⁺ T cell responses also increased with age. Conclusions. In children aged 3-17 years, B-and T-cell responses following IIV receipt showed significant cross-reactivity against A(H3N2) viruses during a vaccine mismatch season.