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.