Seasonal Influenza Vaccination of Children Induces Humoral and Cell-Mediated Immunity Beyond the Current Season: Cross-reactivity With Past and Future Strains

Abstract

Influenza viruses gradually accumulate point mutations, reducing the effectiveness of prior immune protection. Children aged 9–14 years received 2010–2011 trivalent inactivated influenza vaccine (TIV). Vaccination history, hemagglutination-inhibition (HI) titers, and cell-mediated immune responses were assessed to investigate the cross-reactivity with past and future influenza virus strains. 2010–2011 TIV induced significant T-cell responses and HI titers of ≥160, with a fold-rise of ≥4 and titers of ≥100 maintained for >7 months in the majority of children. Pre-existing memory B cells in these children differentiated quickly to antibody-secreting cells to the new vaccine antigens. Children vaccinated in the previous year maintained high HI titers well into 2010, demonstrating elevated HI titers against A/Perth/16/2009, the future (in 2010–2011) H3N2 component. Prior vaccination enhanced CD8⁺ T-cell responses to A/Perth/16/2009. Children vaccinated with the prior 2009–2010 seasonal vaccine also demonstrated higher preexisting levels of interferon γ–secreting CD4⁺CD69⁺ T cells to 2009 pandemic influenza A(H1N1). Children previously vaccinated with 2009–2010 seasonal influenza vaccine also showed greater expansion of tumor necrosis factor α–secreting CD8⁺CD69⁺ T cells to 2009 pandemic influenza A(H1N1) upon vaccination in the 2010–2011 season than those who were not previously vaccinated. Seasonal influenza viruses continuously drift, which allows them to circumvent protective immunity, but conserved epitopes provide immunological cross-reactivity in children through either vaccination directly or through prime/boost in the prior influenza season.