Candida has become the fourth leading cause of nosocomial bloodstream infections. The incidence of hematogenous disseminated and mucocutaneous candidiasis continues to rise in parallel with tnhen increasing population of immunocompromised people. Several species of Candida may be responsible for the various forms of candidiasis, but C. Albicans is by far the most prevalent cause. Despite the importance of this species, there is still much to learn about C albicans-host interactions. For many years, the dogma has prevailed that specific antibodies do not play a protective role against disseminated candidiasis, even though some papers since the 1960s have suggested this dogma is wrong. Recently, work in the investigators laboratory and in those of a few others gives strong support that antibodies with the correct specificity are protective. At the very least, the importance of antibodies needs to be carefully re-evaluated. The investigators overall hypothesis is that antibodies with the correct specificity help protect the host against candidiasis. The investigator has isolated two monoclonal antibodies that react with the cell surface of C. Albicans yeast cells. Bothe antibodies are IgMs and both agglutinate yeast cells, but one (MAb B6.1) protects mice against disseminated candidiasis and the other (Mab B6) does not. The thrust of this application is to study the epitopes to which these antibodies are specific and define possible mechanisms by which Mab B6.1 protects mice. To this end, the Investigator will perform the following specific aims. 1. Characterize the epitopes to which Mab B6.1 and Mab B6 are specific. 2. Investigate possible mechanisms by which Mab B6.1 protects, but Mab B6 does not. 3. Determine if antibodies with Mab B6.1 specificity are present in sera of normal people, from patients who died of disseminated disease, and from patients who recovered from disseminated candidiasis. These studies should yield important insights into C. Albicans-host interactions. The results may become applied to prevention and, possibly, therapy of disseminated candidiasis.
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