National Institutes of Health, National Institute of Allergy and Infectious Diseases, Contract Management Branch, Solar Bldg., Room 3C07, 6003 Executive Blvd. MSC 7610, Bethesda, MD 20892-7610

A -- MOLECULAR PATHOGENESIS VIROLOGY AND IMMUNOLOGY LABORATORY POC Bruce Anderson, (301) 496-8371 The National Institute of Allergy and Infectious Diseases plans to initiate negotiations to extend and complete Georgetown University Contract No. N01-AI-45179 entitled "Molecular Pathogenesis, Virology and Immunology Laboratory". Georgetown currently interacts with Cornell University (N01-AI-35164) to design and analyze experiments related to pathogenesis and natural history of hepatitis viruses using the woodchuck animal model, as well as to evaluate candidate preventative and therapeutic interventions. This will be a 9.5-month extension, from October 16, 1998 -- August 1, 1999, which will allow Georgetown to complete analyses on current lifetime therapies and critical immunological studies defining mechanisms of chronicity. Specifically the Contractor will be responsible for: completion of antiviral studies posed for 1998-1999; completion of the ongoing lifetime therapy studies; development and refinement of cytokine assays; further definition of early markers of disease progression; examinationof cytokines as antivirals both in vitro and in vivo; completion of first antiviral study in HDV-infected woodchucks; completion of the first anticancer therapies in chronic woodchucks; confirmation of HBV-transgenic mouse model for hepatitis B; reorganization of the methods and mechanisms presently used to test new drugs against hepadnaviruses; and, processing and publishing of experimental results. This Georgetown contract is an essential arm in the processing of unique woodchuck samples from the recently extended experimental viral hepatitis woodchuck colony contract at Cornell University. These two contracts together have helped define the hepadnaviral disease process in woodchucks, invented assays for screening sera and tissues for key disease markers, and interpreted the data jointly. Results from testing candidate anti-hepatitis drugs in the woodchuck/woodchuck hepatitis virus model are highly mirrored when the same drugs are given to humans infected with hepatitis B. Many of the results of antiviral testing against the woodchuck hepatitis virus are determined at Georgetown from assays created on site. In addition, Georgetown houses an in vitro drug screening model for hepatitis B which allows it to do antiviral combination studies for efficacy and toxicity which may segue into woodchuck studies. There are critical long-term experiments ongoing at Cornell-several of which were instigated conceptually by Georgetown and by whom determination of final results will be necessary. Answers from these experiments will be extremely valuable for establishing long-term efficacy of experimental drugs against chronic disease and subsequent liver tumors. Georgetown is the only known source for meeting the requirements of this highly specialized work; therefore, seeking full and open competition would only result in unacceptable delays in fulfilling the requirements of the NIAID. See numbered Note 22. (0167)

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