Characterization of an IgA-eliciting mechanism to improve oral vaccine 2252

Abstract Description Current parenteral vaccines effectively generate systemic immunity through IgG antibodies but are not efficient in producing a robust mucosal immunity, mediated by IgA antibodies, which are essential for preventing infections by mucosal pathogens. Here, we explore how key inflammatory molecules, TRIF and IL1R1, inhibit IgA production in the murine intestine. In absence of infection, we observed that Trif- and Il1r1-deficient mice harbored a higher percentage of IgA-bound bacteria and free IgAs in stools compared to control mice. This boost in IgA correlates with the enrichment in the Peyer’s patches of follicular helper T cells, which are critical for germinal center formation. Furthermore, increased IgA production in absence of TRIF and IL1R1 correlates with elevated retinoic acid metabolism in Peyer’s patches, aligning with existing knowledge regarding its role in IgA production. We also identified an uncharacterized bacterium from the Muribaculaceae family as a target of these intestinal IgAs, suggesting its potential as an antigen vector for intestinal immunizations. Additionally, oral immunization with protein-based vaccines elicited heightened IgA responses in the intestine of Trif- and Il1r1-deficient mice compared to control mice. Overall, our findings highlight the specificity of the mechanisms, within the Peyer’s patches, leading to mucosal immunity, paving the way for more targeted and effective mucosal and oral vaccines. Funding Sources Moderna Project # 835603 RWJF Grant Project # 826399 Topic Categories Mucosal and Regional Immunology (MUC)