Involvement of Type I Interferon pathway in generating antibody responses elicited by DNA vaccination. (52.7)

Abstract

Abstract Recent human study data suggests that DNA immunization can substantially enhance the protective antibody responses elicited by conventional influenza vaccines, but the mechanism of such actions is completely unknown. The current study was designed to explore the roles of innate immunity in regulating acquired immunity elicited by influenza vaccines. Innate pattern recognition receptors (PRRs), and their downstream signaling molecules, were investigated for their effect on DNA vaccination. Of particular interest was the type I interferon (IFN) pathway and its effects on the antigen-specific antibody response. Wild type C57BL/6 mice and selected Interferon Regulatory Factors (IRFs) knockout mice were immunized with DNA vaccines expressing the hemagglutinin antigen (HA) of H1 subtype influenza virus. Mouse serum anti-H1HA antibodies and non-antigen specific cytokine profile analysis showed that deletion of the IRF3 pathway alone did not result in a significantly decreased antibody response but deletion of both the IRF3 and IRF7 pathways led to a dramatic reduction of the anti-HA antibody response. Interestingly, deletion of IL-1 signaling did not significantly affect the anti-HA antibody responses. These results suggested that the IFN pathway does play an important role in shaping the antigen specific antibody response to DNA vaccines and may require the involvement of more than one key regulatory molecule.