Friday, July 17, 2015
Grand Hall and Gallery, Ground Floor & 1st Floor (Maritim Hotel)
Cholera toxin (CT) has been long used as a mucosal immunogen and adjuvant to induce both systemic and mucosal humoral responses to itself and co-delivered protein antigens. Additionally, CT oral or intracolonic inoculation has recently been shown to expand non-inflammatory Th17 cells in the mucosal sites. We observed an enlarged CT-induced homeostatic Th17 population in the intestine and a correspondingly 10-fold higher CTB specific serum IgG response in B6.IgA-/- mice compared to wild type (WT) B6 mice after CT immunization. Using 16S rDNA Microbiome Sequencing, we found a difference of intestinal microbiota composition between B6.IgA-/- mice and WT B6 mice, particularly a higher prevalence of segmented filamentous bacteria (SFB) in the ileum of B6.IgA-/- mice. We asked whether the combined effect of CT and the intestinal microbiota leads to the amplified intestinal Th17 population and increased humoral responses in B6.IgA-/- mice after CT immunization. Oral administration of vancomycin, which resulted in the ablation of intestinal gram-positive bacteria including SFB, greatly dampened both CT immunogenicity and adjuvanticity. The differential CT responses in B6.IgA-/- mice and WT B6 mice disappeared when we crossed WT B6 mice back to female B6.IgA-/- mice and immunized littermate F2s, which had the same microbiota composition by 16s rDNA sequencing. Using germ free and Altered Schaedler flora (ASF) gnotobiotic mouse models, we confirmed that SFB and other commensal bacteria are actively involved in CT immunogenicity and adjuvanticity after mucosal immunization, providing us with new insights into mucosal vaccine design and development.