Antibodies and fungi: an evolving paradigm with opportunities for the development of new antifungal therapies and vaccines.

The role of antibody immunity in protection against fungal infections has been uncertain for decades. This is in sharp contrast to bacteria, viruses, and protozoa where antibody immunity is widely acknowledged to contribute to protection. This raises the questions: Do protective antibodies against fungi exist?; Why has it been so difficult to demonstrate conclusively that antibody immunity protects against fungi?; Does antibody immunity influence the course of fungal infections? The issue of whether antibody immunity contributes to host defense against fungi is no longer academic. In recent years there has been a marked increase in fungal infections associated with the HIV epidemic and immuno-suppressive therapies. Systemic mycoses in immunocom-promised patients are difficult to treat effectively because antifungal therapy frequently fails to eradicate the infection in the setting of defective immunity. For example, C. neoformans infections are usually incurable in AIDS patients. In the 1960s Morris Gordon and collaborators established that antibody administration could enhance the efficacy of antifungal chemotherapy [1]. Hence a better understanding of the role of antibody immunity may help in the design of effective vaccines and/or antibody-based therapies. Numerous investigators have studied the function of antibody immunity in host defence against fungi [2]. A role for antibody immunity in protection against individual pathogens is usually established by correlating the presence of serum antibody with protection and/or demonstrating protection after passive antibody administration. Among the medically important fungi, the role of antibody immunity has been most extensively studied for C. albicans and C. neoformans [2]. For both fungi studies with polyclonal antibody reagents (i.e. immune sera) have produced conflicting evidence for and against the importance of antibody immunity [2]. Until the mid-1980s all studies of antibody protection against fungi utilized poly-clonal reagents. In 1987 Dromer et al. [3] demonstrated that a monoclonal antibody (mAb) was protective against C. neoformans and this observation marks the beginning of new era in the study of antibody function against fungi. In the past decade, experiments with mAbs have established the existence of protective and non-protective antibo-dies against C. albicans [4,5] and C. neoformans [3,6,7]. Furthermore, some mAbs against the C. neoformans cap-sular polysaccharide have been shown to function as blocking antibodies that can enhance infection and interfere with the function of protective antibodies [8]. Hence there is now evidence for "good" and "bad" antibodies against fungi. Protection studies with mAbs suggest an explanation for the inconclusive and often contradictory results obtained from …