SUMMARY – CORE C (CLINICAL CORE) Core C (Clinical Core) will support the overall mVACS program goal to develop modified mRNA vaccines to eliminate C.difficile infection (CDI) by developing an infrastructure for CDI human subject identification, specimen biobanking, and metadata collection to study the stool microbial ecology and C. difficile-specific adaptive immune responses in humans. Core C (Clinical Core) will lead enrollment of patients, acquisition, storage, and processing of specimens and associated clinical data in a biorepository and manage the distribution to individual projects. In addition, longitudinal clinical outcomes will be followed after sample collection. We propose the following specific aims: (1) to establish a recurrent CDI biorepository and clinical database, capturing stool samples and demographic data at the time of diagnosis, across a range of ages and comorbidities; (2) to develop a longitudinal cohort of CDI subjects enrolled at first disease recurrence, for in parallel deep microbial and immune profiling, with linkage to longitudinal clinical outcomes; and (3) to provide samples and clinical metadata from the established biorepository and cohort to allow testing and validation of in vitro and animal model findings from Project 1 (Vaccine Development), Project 2 (Antigen Discovery), and Project 3 (Immunology). Core C (Clinical Core) will facilitate correlation of clinical features of rCDI and its outcomes with findings in Project 1 (Vaccine Development), Project 2 (Antigen Discovery), and Project 3 (Immunology), as well as the genomic findings in Core B (Genomics Core) in order to identify and refine vaccine targets that may increase efficacy.