Memory B cells with gut-homing potential are generated by a prototype anti-enterotoxigenic E. coli vaccine given by intradermal immunization with LT(R192G) as an adjuvant (MUC3P.945)

Abstract

Abstract Lymphocytes that express α4β7 integrin can home to the gut mucosa through interactions with MAdCAM-1 addressin on the intestinal endothelium. α4β7+ Ag-specific plasmocytes and memory B (BM) cells can be found after infection or experimental challenge with enteric pathogens as well as mucosal immunization, yet gut-homing B cells have not been reported in high frequencies in humans after parenteral immunization. Intradermal (ID) immunization is an attractive delivery route for enteric vaccines due to a potential connection between the skin and gut. Mucosal responses may be further enhanced by the addition of adjuvants such as LT(R192G), an attenuated form of the enterotoxigenic E. coli (ETEC) LT toxin. We analyzed BM cell generation in volunteers with two prototype vaccines based on the ETEC class 5a fimbriae tip adhesin CfaE with LT(R192G) by ID delivery. We observed both anti-CfaE and -LTB IgG and IgA BM cells, with a higher prevalence of Ag-specific IgG BM cells. Interestingly, anti-LTB IgA and anti-CfaE IgG BM cells were elicited at frequencies similar to those reported after ETEC infection, whereas anti-LTB IgG BM cells were found in higher frequencies after ID immunization compared to infection. The frequencies of anti-CfaE and -LTB IgG BM cells were similar in α4β7+ and α4β7- fractions, while the majority of anti-CfaE and -LTB IgA BM cells were α4β7-. These data suggest that the adjuvant LT(R192G) may be used to enhance mucosal BM responses following ID immunization.