Immunogenicity of influenza vaccines: Evidence for differential effect of secondary vaccination on humoral and cellular immunity

While currently used influenza vaccines are designed to induce neutralizing antibodies, little is known on T cell responses induced by these vaccines. The 2009 pandemic provided us with the opportunity to evaluate the immune response to vaccination in a unique setting. We evaluated both antibody and T cell responses in a cohort of public health care workers (18-52 years) during two consecutive influenza seasons from 2009 to 2011 and compared the MF59-adjuvanted pandemic vaccine with the unadjuvanted seasonal subunit vaccine that included the pandemic strain [The study was registered in the Netherlands Trial Register (NTR2070)]. Antibody responses were determined in serum by a hemagglutination inhibition assay. Vaccine-specific T cell responses were evaluated by detecting IFN-γ producing peripheral blood mononuclear cells using whole influenza virus or vaccine-specific peptide pools as stimulating antigens. Mixed effects regression models were used to correct the data for influenza-specific pre-existing immunity due to previous infections or vaccinations and for age and sex. We show that one dose of the pandemic vaccine induced antibody responses sufficient for providing seroprotection and that the vaccine induced T cell responses. A second dose further increased antibody responses but not T cell responses. Nonetheless, both could be boosted by the seasonal vaccine in the subsequent season. Furthermore, we show that the seasonal vaccine alone is capable of inducing vaccine-specific T cell responses, despite the fact that the vaccine did not contain an adjuvant. In addition, residual antibody levels remained detectable for over 15 months, while T cell levels in the blood had contracted to baseline levels by that time. Hereby, we show that pandemic as well as seasonal vaccines induce both humoral and cellular responses, however, with a different profile of induction and waning, which has its implications for future vaccine design.