This application for a Sexually Transmitted Diseases (STD) Research Center is a consortium agreement between Indiana University, Northwestern University, and the University of Wisconsin at Madison. It is a multidisciplinary project with a primary focus on those pathogens which are most prevalent in the United States and which produce the most morbidity in women. A central theme is development of a better understanding of structure and function of microbial surface components, factors which regulate them, and interactions with the immune system. Eight projects are proposed. One has as its objective determination of structural variations in herpes simplex glycoproteins which relate to functional differences. A second is focused on pilus antigenic variation in Neisseria gonorrhoeae, its classification, and correlation with antibody reactivity in infected people. Another project focuses on further characterization of the neisserial common antigen OMP-MC in terms of its surface exposure and degree of conservation of peptide structure in order to identify potentially protective epitopes. Two projects will study the immune response to Chlamydia trachomatis infections; one will focus on epitope- specific antibody response to the major outer membrane protein of the organism and the other on the T cell response to the putative hypersensitivity antigen. Two projects are directed at increasing our understanding of regulation of the replication of papillomaviruses. One of these will examine the effect of pregnancy on virus replication while the other will concentrate on defining the molecular factors which regulate gene expression. Another project will prospectively evaluate the efficacy of three behavioral intervention models in reducing the incidence of recurrent chlamydial infection. These projects will be supported by four cores; an administrative one, a clinical one which will gather data and specimens for all of the above projects, a biostatistics one which will assist in further study design and data evaluation, and a chlamydia/laboratory core which will process specimens for each of the projects and provide chlamydia cultures, serologies, and immunotyping. Extensive collaboration between the projects exists and will be reinforced at regional scientific/administrative meetings which will be held every four months. In addition, research developmental funds are requested and examples of the types of projects for which these might be used are provided. An evolving relationship between the Indiana University School of Medicine and the University of Moi in Eldoret, Kenya is also described.
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