The Role of CD4 T Cell Mediated Immunity in Pandemic Influenza Protection
Methods: To further investigate the role of influenza-specific CD4 T cells after immunization with a drifted H5 influenza vaccine, subjects previously enrolled in a trial of an inactivated A/Vietnam/1203/2004 H5 vaccine and previously naïve subjects were immunized with an inactivated subunit A/Indonesia/5/05 H5 vaccine. Neutralizing antibody responses were measured by microneutralization assay and CD4 T cell responses were measured using IFN gamma Elispot assays following ex-vivo stimulation with pools of peptides representing distinct influenza proteins.
Results: In previously primed individuals, neutralizing antibody responses were greatly accelerated. While vaccination induced detectable CD4 T cells specific for hemagglutinin (HA) and the internal viral proteins in both groups, previously primed individuals had greater HA-specific CD4 T cells at the pre-vaccination timepoint and mounted a more robust CD4 T cell response to HA-specific peptide epitopes at day 14 post vaccination. There were no differences between vaccination groups when CD4 T cell responses to the much more conserved NP protein were examined. Interestingly, neutralizing antibody responses were significantly higher in individuals able to mount a CD4 T cell response to the HA but not the NP protein.
Conclusion: These findings suggest that prepandemic vaccination promotes a broadly cross-reactive and rapid response on challenge with a closely related virus that may be in part attributable to recruitment of an enriched population of HA-specific CD4 T cells. Prepandemic vaccination strategies that include priming of HA-specific CD4 T cells may help to induce broad protection against diverse, potentially pandemic strains of influenza.
S. Alam, None