Our research program is focused toward understanding the virulence of Trichomonas vaginalis through the identification and biochemical characterization of membrane immunogens with important biological properties or functions. Three major areas of research are emphasized: i) antigen analysis studies targeting potential (glyco)proteinaceous substances as candidates for vaccines or immunodiagnostic tests; ii) the surface parasitism of host cells by T. vaginalis using in vitro and in vivo models; and iii) production of monospecific and monoclonal antibody against highly immunogenic surface proteins of T. vaginalis for enhancing our knowledge of immunochemical properties of specific antigens and dissecting the nature of the parasitism by trichomonads to urogenital-vaginal tissues and cell cultures. A variety of technology will be employed which include standard radiolabeling procedures, chromatographic?and electrophoretic methods, hybridoma monoclonal antibody reagents, and electron microscopy. Our long term goal is to identify highly immunogenic membrane protein antigens of T. vaginalis which possess key biologic functions, such as ligands involved in host parasitism of cell surfaces, essential for infection of human hosts. Initial data are provided in the Preliminary Results section which indicate the feasibility of this proposed research program. In addition to studies described above, the virulence of Treponema pallidum will be examined through the immunobiochemical characterization of specific outer envelope proteins implicated as adhesins recognizing fibronectin on host cell surfaces. The chemical dissection of fibronectin and protease-derived fibronectin fragments will be emphasized in order to permit analysis of precise domains on the fibronectin polypeptide responsible for binding treponemal ligands. As above, a combination of up-to-date methodologies will be employed. Preliminary studies suggest that definition of the infectious process and precise virulence determinants may be possible with these approaches.
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