Novel C. Difficile Vaccine Using Nano-vesicle Delivery System - Abstract
Clostridium difficile is a Gram-positive, spore-forming bacteria that causes severe diarrhea and C.
difficile infection (CDI) ranks fourth among the highest number of infections in hospitals. Annually, CDI
causes as many as 500,000 infections and 15,000 deaths in the USA and costs up to $4.8 billion.
Development of effective vaccines is important for prevention and treatment of CDI. There are C. difficile
vaccine candidates that are comprised of inactivated toxins A and B (called toxoids) and none have
demonstrated significant clinical efficacy in CDI prevention. We propose to use our novel vaccine
delivery platform that presents antigens on the surface of nanoparticles derived from recombinant outer
membrane vesicles (rOMVs) of probiotic E. coli strains. rOMVs represent a promising, low-cost vaccine
delivery method with improved features over conventional vaccines including better antigen
presentation, technical readiness, simplicity, thermostability and flexibility of the manufacturing
process. The OMV-based vaccine platform has been validated clinically by an approved vaccine
(Bexsero, GSK) that is efficacious in prevention of group B meningococcal infections. Versatope’s
scientific founders have demonstrated that our rOMV-based vaccines containing polypeptide antigens
and poly-N-acetylglucosamine (PNAG, a conserved bacterial surface polysaccharide) are effective in
prevention of bacterial and viral infections in animal models. In this study, we hypothesize that C. difficile
toxoids A and B, and PNAG presented on the surface of E. coli rOMV will be displayed in a three-
dimensional antigenic complex to generate strong and long-lasting immunity responses that may result
in a better protection against CDI than the conventional vaccines composing purified toxoids formulated
with the Alum adjuvant. The primary objective of this proposal is to select a novel C difficile vaccine
candidate(s) for further evaluation and development.
