Brucellosis Vaccine Ag85a-S2 activates cGAS-Sting Signaling Pathway in Intestinal Mucosal Cells

Brucellosis is a zoonotic disease caused by Gram-negative bacteria, resulting in an economic loss of billions of USD per year. Most of the Brucellosis vaccines in the application are the whole bacteria vaccines, which typically have high toxicity and low immunogenicity. We recently developed an S2 vaccine adjuvanted with Ag85A (Ag85A-S2), which greatly improved the immunogenic properties of S2. However, the mechanisms of Ag85A-S2 remained elusive. Here, we found that Ag85A-S2 activated cGAS-STING pathways both in intestinal mucosal cells and in a cGAS knockout cell line in vitro. We demonstrated that the cGAS knockout significantly downregulated the abundance of interferon and other cytokines induced by Ag85A-S2. In sum, Ag85-S2-mediated enhancement of immune responses was dependent on both cGAS and STING. Our results provided a new strategy for preventing Brucellosis from livestock, which might reduce the dosage and potential toxicity compared to the traditional S2 vaccine. Overall design: We knocked out cGAS and stimulated this knockout cell line with Ag85a-S2.