The objectives of the Virology and Immunology Core are: i) To obtain and characterize stocks of the various HIV-i entry inhibitors that will be evaluated in the in vitro and macaque model systems in Research Projects I and III, or provided to Research Project II for formulation studies. 2) To characterize the antiviral potency and cytotoxicity of inhibitor formulations created in Research Project II. 3) To perform viral load assays for the dual virus-challenge experiments outlined in Research Projects I and III (under a Consortium Agreement with Dr. Steven Wolinsky at Northwestern University). 4) To support Dr. Veazey's studies in Research Project III that are aimed at determining whether local immune responses are stimulated by mucosally applied viruses and/or viral antigens. The Core Leader will be John P. Moore, Ph.D, and the Core will be located at the Weill Medical College of Cornell University, New York, NY. Its function will be to act as a central resource to support the individual Research Projects. The Core will obtain sufficient quantities of suitable entry inhibitors for use in all three Research Projects, and determine the potency of these inhibitors against a range of HIV-i isolates in vitro, using well-established assays based on primary human and rhesus macaque lymphocytes, macrophages and dendritic cells. This work will ensure that only bonafide, active reagents are used in each of the Research Projects. The Core will identify which combinations of inhibitors are most suitable for further evaluation in the in vitro model systems (Research Project I). The Core will help to evaluate new entry inhibitor formulations and delivery methods created in Research Project II. The Core will participate in the determining the outcome of experiments using the rhesus macaque vaginal challenge model (Research Project III), particularly when the animals are challenged with more than one virus simultaneously, and will also assist with the analyses of HIV-i virus- or antigen-induced mucosal immune responses. Dr. Steven Wolinsky of Northwestern University will contribute to the work of the Core under a Consortium Agreement. Dr. Wolinsky's specific role will be based around the design and use of PCR-based assays for the detection and quantification of viral genomes, both for use in Project III (to analyze the outcome of macaque vaginal challenges involving more than one virus) and Project I (to analyze the infection of cell culture and cervical tissue explant systems with defined challenge viruses). The majority of Dr. Wolinsky's funding for this work will be provided by the International Partnership for Microbicides, as outlined in the Program Overview section of this application.
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