Humoral and cellular immune responses in children given annual immunization with trivalent inactivated influenza vaccine

Background: There have been no prior reports of the frequency of circulating influenza-specific, interferon gamma-producing memory CD4(+) and CD8(+) T-cells in healthy children who have received multiple influenza immunizations. Methods: We evaluated 21 previously immunized children, ages 3 to 9 years, before and I month after administration of trivalent inactivated influenza vaccine. Frequencies of influenza-specific CD4(+) and CD8(+) T-cells stimulated with trivalent inactivated influenza vaccine or A/Panama (H3N2) virus were determined by flow cytometry, and antibody responses to vaccine strains and a drifted H3N2 strain were measured by hemagglutination inhibition assay and neutralizing antibody assays. Results: Mean change in CD4(+) and in CD8(+) T-cell frequencies after immunization was 0.01% (P > 0.39) with postimmunization CD4(+) frequencies higher than CD8(+) frequencies. Children with more previous vaccinations had a higher baseline frequency of CD4(+) T-cells (P = 0.0002) but a smaller increase or even a decline from baseline after immunization (P = 0.003). An association between age and change in frequency was not detected. Baseline geometric mean titers (GMTs) and seroprotection rates were significantly higher in older children against A/Panama (neutralizing baseline GMT, P = 0.0488) and A/New Caledonia (hemagglutination inhibition baseline GMT and seroprotection, P < 0.0297). Baseline GMTs against B/Hong Kong were not associated with age or quantity of prior vaccinations. Conclusions: These findings suggest that children may plateau in CD4(+) T-cell responses to influenza antigens with repeated exposures and that the number of exposures may play a large role in building a memory CD4(+) T-cell response to influenza A, perhaps independently from age.