Cryptococcus neoformans causes disease about 10% of AIDS patients. Cryptococcal infections in AIDS are very difficult to treat and are often fatal. This proposal requests funds to obtain information necessary for developing protective mouse monoclonal antibodies (MAbs) for human therapeutic use. Passive antibody therapy for C. neoformans infections would be a novel approach for the treatment of this infection. I have already generated a extensive library to identify the most protective mouse MAb for human use. I will use a variety of animal models to determine the conditions in which my MAbs are effective in mediating protection. I will study the efficacy of passive MAbs have been identified. I plan to screen the library to identify the most protective mouse MAb for human use. I will use a variety of animal models to determine the conditions in which my Mags are effective in mediating protection. I will study the efficacy of passive Mags administration in combination with antifungal drugs. The structural and functional characteristics that contribute towards protective efficacy in anti- cryptococcal antibodies will be studied. Of particular interest are the role of antibody isotype, affinity, and epitope specificity in conferring protection. In-vitro experiments with macrophages will study the ability of the Mags to promote opsonization and killing of the fungus. The antigenic composition of clinical isolates will be studied with our MAb library. The experiments proposed here will provide crucial data necessary for taking some of our highly protective Mags to a clinical trial in AIDS patients.
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