Oklahoma C. difficile U19 Challenge Core

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Project Summary (Challenge Core) The central goal of the Oklahoma C. difficile U19 program is to advance a second-generation vaccine for C. difficile by revealing mechanisms that limit protective vaccine-induced responses. In order to achieve these goals, challenge experiments are required whereby relevant animal models are used to test vaccine efficacy. Given that the U19 program has 3 distinct but complementary Research Projects and that synergistic interaction between those projects is desirable, standardization of the challenge experiments is a prudent and essential measure. Towards, this goal, we will build upon our experience with murine and hamster challenge models to develop a coordinated ‘Challenge Core’ which will provide a standardized service to each of the Research Projects. In Specific Aim 1, a single infection murine challenge model will be further developed as a core service. In Specific Aim 2, a repeat infection model will be further optimized and provided as a core service. In Specific Aim 3, a hamster challenge model will be established and provided as a core service for promising vaccination modalities. Importantly, all approaches are utilized currently by the Ballard and/or Lang laboratories, but will be further developed to ensure standardization and experimental rigor with regard to environment, microbiome, reagents, methods, and readouts. A dedicated core will also relieve the burden on individual projects and facilitate rigorous experimentation. The core service will be made available to other investigators interested in C. difficile research and will lower the barrier to setting up challenge experiments for specific projects.