Cryptococcus neoformans: Paradigm for the Role of Antibody Immunity Against Fungi?

Abstract

Cryptococcus neoformans is an encapsulated fungus that is a frequent cause of life-threatening infections in patients with AIDS. C. neoformans has many similarities with encapsulated bacteria such as S. pneumoniae and H. influenzae for which antibody immunity is important in protection. However the role of antibody immunity in protection against C. neoformans has been controversial. Experiments with polyclonal sera have produced conflicting evidence for and against the importance of antibody immunity in host defense. Experiments with monoclonal antibodies (mAb) to the C. neoformans capsular polysaccharide (CPS) have revealed the existence of protective, non-protective and disease-enhancing mAbs, suggesting that the divergent results obtained with polyclonal preparations may be a result of relative proportion of protective and non-protective antibodies in immune sera. Administration of protective mAbs can prolong survival, decrease organ fungal burden, and reduce serum polysaccharide antigen. In vitro experiments suggests that protective mAbs modify the course of infection by enhancing effector cell function against C. neoformans. Addition of mAb to antifungal drugs enhances their efficacy against C. neoformans in vivo and in vitro. Human-mouse chimeric antibodies with activity against C. neoformans have been constructed. A highly immunogenic capsular polysaccharide-protein vaccine has been synthesized that elicits protective antibodies in mice. Antibody immunity elicited by conjugate vaccines or provided by passive administration may be useful in the prevention treatment of human cryptococcal infections.