1061The Role of CD4 T Cell Mediated Immunity in Pandemic Influenza Protection

Background. Vaccination against pandemic influenza poses significant challenges as the viral strain that will be responsible for the next influenza pandemic is unpredictable. Given the time lag between initiation of a pandemic and significant vaccine production, a pandemic vaccine will rarely be available until after significant viral circulation has occurred. One possible strategy to circumvent this limitation is to prime individuals against potentially pandemic strains before a pandemic strikes. 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. Disclosures. All authors: No reported disclosures.