SUMMARY-SMALL ANIMAL CORE A critical component of our vaccine development program is efficacy testing of candidate antigens in murine models of C. difficile infection. The Small Animal Core of our program will achieve this goal and identify lead antigens for the development of novel vaccines to prevent against CDI. The Small Animal Core will be led by Dr. Eric Skaar. The Skaar laboratory has significant experience in the murine model of C. difficile infection and has also developed a new live C. difficile vaccine model in mice as described in Project 2. In addition, the Skaar laboratory has experience testing the therapeutic efficacy of both small molecules and antibodies in murine models. This experience will be used to guide the creation of a Small Animal Core to test the efficacy of lead antigens developed by this program. The Small Animal Core will benefit from the expertise of the Translational Pathology Shared Resource (TPSR) which includes access to a board-certified veterinary pathologist with experience in in vivo modeling of human disease, including molecular pathology, toxicopathologic assessment, and digital pathology as well as advanced training in veterinary anatomic pathology and murine models. The Small Animal Core will receive optimized candidate antigens from Scientific Core 2. These proteins will be tested for efficacy in appropriate murine models of CDI. Candidate antigens will be tested alone or in combination. Combined, the efforts of the Small Animal Core will result in the identification of lead antigens for the development of novel vaccines that protect against infections caused by C. difficile.