Mycology Research Unit: In Vivo Induced Fungal Antigens

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DESCRIPTION (provided by applicant): The Mycology Research Unit: In Vivo Induced Fungal Antigens Program Project consists of four interrelated research projects and a Clinical Resource Core organized around the identification of C. albicans and A. fumigatus proteins expressed during human infections. The unifying hypothesis of the Program is that selected in vivo induced proteins contribute to the pathogenesis of invasive fungal infections and have potential applications as vaccine, diagnostic and therapeutic targets. The Core, run by Dr. Wingard (University of Florida; UF) will collect sera and tissue samples from patients with C. albicans and A. fumigatus infections. The sera will be used extensively in each of the projects. In Project 1 (Candida antigens involved in site-specific virulence), Dr. Nguyen (UF) will study in vivo induced antigens that she and Dr. Clancy identified by screening a genomic expression library with sera from patients with candidiasis. The contributions of the in vivo induced antigens to pathogenesis will be assessed in models of mucosal and systemic candidiasis. She will also characterize the humoral immune response against recombinant antigens in the serum of patients with candidiasis and controls. In Project 2 (A proteomic approach to host humoral immune response), Dr. Liu (UC-Irvine) will construct C. albicans cell wall protein and blood-induced protein arrays and probe them with sera from patients who survived or died from candidemia. Her goal is to identify immunogenic antigens associated with good prognosis. In Project 3 (Candida in vivo expressed protein as a mannan carrier), Dr. Cutler (TRIC,La) will use cell wall antigens identified in Projects 1 and 2 as carrier proteins in a conjugate mannan vaccine against hematogenous candidiasis. Finally, in Project 4 (Identification of In vivo Induced A. fumigatus Antigens), Dr. Clancy (UF) will adapt the serum-based screening that he and Dr. Nguyen developed to screen A. fumigatus expression libraries. In vivo induced A. fumigatus antigens can then be studied using our investigations of C. albicans antigens as models.