PROTECTIVE ANTIBODY FOR CRYPTOCOCCAL INFECTIONS

DESCRIPTION: Cryptocococcus neoformans is a yeast-like fungus with a polysaccharide capsule. The capsule is a well characterized marker of virulence, and the organism is neurotropic. The majority of cryptococcal infections involve the brain where the fungus causes life threatening meningoencephalitis in approximately 10 percent of patients with AIDS immunosuppression and which is usually incurable and often fatal. The difficulties encountered in treating cryptococcal infections in immunosuppressed (AIDS) patients have renewed interest in the potential of immunotherapy as an adjunct to antifungal therapy. One option for immunotherapy is passive antibody administration with protective antibodies. Dr. Casadevall has identified several protective murine monoclonal antibodies to cryptococcal infections. Studies in mice indicate that the monoclonal constant region domain of immunoglobulin isotype is a critical parameter of protective efficacy. The proposed research is to study the role of isotype in protective efficacy against C. neoformans and the specific aims are: 1. To isolate isotype switch variants from protective and non-protective lonal antibodies previously generated in Dr. Casadevall's laboratory. 2. To characterize the isotype switch variants by serological and molecular iques. 3. To study the contribution of isotype class to protective efficacy against oformans using in vitro and in vivo systems.