CANDIDA ALBICANS PROTECTIVE EPITOPES

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DESCRIPTION (Adapted from applicant's abstract): The incidence of hematogenous disseminated and mucocutaneous candidiasis continues to rise in parallel with the increasing number of immunocompromised peopole. Several species of Candida can cause candidiasis but C. albicans is the most prevalent and there is still confusion regarding host defence mechanisms. For years the prevailing dogma is that antibodies do not play a role against disseminated candidiasis even though older papers suggested that antibodies did, in fact, play a role in protection. Recent work shows that antibodies of the correct specificity are in fact protective. Mice immunized against C. albicans cell surface phosphomannoprotein (PMP) can produce protective antibodies. A monoclonal antibody (MAb B6.1) was isolated that reacts with a beta-1,2-trimannose in the PMP and this MAb heightens resistance of normal and neutropenic mice to hematogenous disseminated candidiasis. To enhance further development of these antibodies the applicant proposes to use a phage display library to isolate a family of peptides that structurally mimic the protective carbohydrate epitope and have varying binding affinities to MAb B6.1. These peptides will be useful in testing the hypothesis that peptide mimetics can induce antibody responses that protect mice against hematogenous disseminated candidiasis. The plan is to 1) select clones from a phage display library that specifically combine with MAb B6.1; 2) use the sequence data to identify a family of peptide mimetics based on their relative binding affinities to MAb B6.1; 3) To demonstrate that the peptide mimetics can induce production of antibodies that recognize C. albicans carbohydrate epitopes; and 4) determine the potential protective value of anti-C. albicans responses of mice immunized against the peptide mimetics.