Core B: Animal Studies

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Abstract The overall goal of this P01 is to develop an attenuated vaccine capable of protecting infants and children from respiratory syncytial virus disease, including the tools necessary to test this vaccine effectively in cotton rats and eventually in infants and children. Core B (Animal Model Use and Development Core) supports the development and use of the cotton rat model utilized within this Program Project Grant (P01). The guiding principals for the animal model core are efficient planning and utilization of animals, standardization of processing, reliability of service and consistent evaluation of in vivo data thus serving as a platform to integrate data across the P01. The fundamental expertise provided within the core is laboratory animal medicine and clinical and anatomic pathology. The Core is housed and coordinated in the Department of Veterinary Biosciences. Dr. Stefan Niewiesk, proposed Core Director has been working with viral respiratory infections in cotton rats for the last 15 years and is an active collaborator with the principal investigators for the P01. He is certified in Veterinary Microbiology (German boards) and a diplomate of the European College of Laboratory Animal Medicine. Dr. Krista La Perle (co-investigator), who is a diplomate of the American College of Veterinary Pathology and has worked with Dr. Niewiesk on cotton rat pathology, will provide pathological evaluations for the Core. In Projects 1-3 (Drs. Teng, Peeples, Li), a genetically engineered RSV with reduced pathogenicity and increased immunogenicity will be generated by introducing mutations in the NS-1 protein, G protein, and the polymerase. In Project 4 (Dr. Mejias), the gene expression signature and antibody response of children with mild and severe disease will be determined and compared to the response of cotton rats to vaccination. Core B has developed assays and reagents necessary to support the various projects, and translate markers of immunity defined in patients back to the cotton rat model to improve the evaluation of vaccine candidates.