IMPROVEMENT OF THE COTTON RAT MODEL OF HUMAN DISEASES

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In 1995 the Food and Drug Administration licensed RespiGam TM, a plasma- derived polyclonal IgG formulation, for the prevention of severe respiratory syncytial virus (RSV) pneumonia. In December, 1997, a Biologic License Application was submitted to the FDA for a second- generation RSV preventive, Synagis TM, the first monoclonal antibody ever shown in clinical trials to have efficacy against an infectious agent. These two events underscore the importance of the inbred cotton rat (Sigmodon species) in biomedical research, since all of the preclinical data supporting both drugs were generated in the cotton rat model of RSV infection. However, there are other pressing biomedical issues, involving candidate RSV vaccine safety; HIV, influenza, herpes simplex, measles and parainfluenza viruses; exotic and emerging viruses; and genetic and cancer therapy using adenovirus vectors, for all of which the cotton rat appears to be a preferred model. These issues cannot be addressed adequately because the complexity of the underlying biology requires immunologic and genetic reagents specific for the cotton rat, which are not yet available. We have already begun a program, using methodologies of immunology and molecular biology, to generate the reagents which will allow state-of-the-art studies in this model. The proposed workscope of this application is to develop a library of reagents directed against cotton rat cell-surface antigens, cytokines and chemokines.