Seasonal Influenza Vaccination Of Children Induces Humoral And Cell-Mediated Immunity Beyond The Current Season: Cross-Reactivity With Past And Future Strains

Background. Influenza viruses gradually accumulate point mutations, reducing the effectiveness of prior immune protection.Methods. Children aged 9-14 years received 2010-2011 trivalent inactivated influenza vaccine (TIV). Vaccination history, hem-agglutination-inhibition (HI) titers, and cell-mediated immune responses were assessed to investigate the cross-reactivity with past and future influenza virus strains.Results. 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 gamma-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 alpha-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.Conclusions. 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.