PROTECTIVE ANTIBODIES FOR CRYPTOCOCCAL INFECTIONS

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.