Development of a Novel Mucosal Vaccine Against Clostridium difficile 2261214

Abstract Introduction C. difficile (CD) is the leading cause of antibiotic-associated diarrhea and colitis. Vaccines for CD infection (CDI) have failed in Phase III trials as although serum antibodies induced by systemic immunization can neutralize CD toxins, these vaccines do not impact bacterial colonization and transmission. As such, our lab aims to develop a mucosal vaccine that can neutralize CD toxins, TcdA and TcdB, at mucosal surfaces, while also protecting from bacterial colonization and transmission. We hypothesize that a mucosal vaccine inducing mucosal IgA antibodies against TcdA and TcdB, as well as antibody against surface layer protein (SLP), would prevent bacterial colonization and eliminate a major cause of hospital-acquired infection. Methods We used papilloma-like particles as a mucosal vector to package plasmids encoding TcdA, TcdB, and SLP to form pseudoviruses as the mucosal vaccine. Mice were immunized orally and then tested for production of serum IgG and intestinal/fecal IgA against TcdA, TcdB and SLP, with detection being done by ELISA. Results We found the vaccine induced a significant amount of serum IgG and intestinal IgA antibody against TcdA, TcdB, and SLP. We also challenged mice after oral immunization with the vaccine, and found the mice were protected against weight loss and diarrhea. Fecal CD CFU were also greatly reduced in the immunized mice as compared to unimmunized control mice. Conclusion Our preliminary results indicate that this strategy is warranted for further development of an effective mucosal CD vaccine and can potentially be applied to the development of other mucosal vaccines. Funding Source NIH Topic Categories Vaccines and Immunotherapy (VAC)