Identification of Aim2 as a sensor for DNA vaccines 1

• Published in: The Journal of immunology (1950) Vol. 194; no. 2; pp. 630 - 636
• Main Authors: Suschak, John J., Wang, Shixia, Fitzgerald, Katherine A., Lu, Shan
• Format: Journal Article
• Language: English
• Published: 08.12.2014
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1402530

Recent human study data has re-established the value of DNA vaccines, especially in priming high-level antigen-specific antibody responses, but also raised questions about the mechanisms responsible for such effects. Whereas previous reports have shown involvement of downstream signaling molecules in the innate immune system, the current study investigated the role of Aim2 as a sensor for DNA vaccines. The Aim2 inflammasome directs maturation of the pro-inflammatory cytokines IL-1β and IL-18 and an inflammatory form of cell death called pyroptosis. Both the humoral and cellular antigen-specific adaptive responses were significantly reduced in Aim2 −/− mice in an IL-1β/IL-18 independent manner after DNA vaccination. Surprisingly, Aim2 −/− mice also exhibited significantly lower levels of IFN-α/β at the site of injection. These results indicate a previously unreported link between DNA vaccine induced pyroptotic cell death and vaccine immunogenicity that is instrumental in shaping the antigen specific immune response to DNA vaccines.