Involvement of the Aim2 inflammasome pathway in generating antibody responses elicited by DNA vaccination. (P4313)

Abstract Recent human study data suggests that DNA priming immunization can substantially enhance the protective antibody responses elicited by conventional influenza vaccines, but their mechanisms remain completely unknown. The current study explored 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 is the absent in melanoma 2 (AIM2) protein pathway and its effects on the antigen-specific antibody response. AIM2 is a cytosolic DNA sensor important in both the maturation of the pro-inflammatory cytokines, IL-1b, IL-18, and an inflammatory form of cell death known as pyroptosis. Aim2 knockout mice and wild type controls were immunized with a DNA vaccine expressing the hemagglutinin antigen (HA) of H1 subtype influenza virus. Mouse serum anti-H1HA antibodies and B cell responses revealed that deletion of the Aim2 pathway led to a significant reduction of the anti-HA antibody response. Interestingly, non-antigen specific cytokine profile analysis did not demonstrate a dramatic change in cytokine signaling between wild type and knockout mice. Furthermore, deletion of IL-1 signaling did not significantly affect the anti-HA antibody responses. These results suggested that the Aim2 pathway plays an important role in shaping the antigen specific antibody response to DNA vaccines.