The research described in this competing renewal focuses on three main areas of our current research: a.) Continued development and characterization of model in vitro and in vivo systems, including human xenografts, as targets for STDs including herpes simplex virus type 2 (HS-2), human papillomaviruses (HPVs), Chlamydia trachomatis and human immunodeficiency virus (HIV). b.) Expansion of studies with formulated C31G preparations to optimize delivery and microbicidal activity, including pharmacodynamics of the delivered product. c.) Establishment of formulated alkyl sulfates as topical microbicides that can be applied to the vagina and provide protection from HPVs in addition to the other agents. Formulations that include N-9 or C31G in combination with alkyl sulfates will also be evaluated. The application will have four main projects including: The first Project will focus on the xenograft model and the demonstration of the efficacy of the alkyl sulfate compounds. Cellular and enzymatic profiles of the xenografts will be compiled. The second Project will focus on continued studies with C31G, alone and ir combination with alkyl sulfate microbicides. The pharmacodynamics in humans and in vitro models will be studied. The third Project will focus on the three selected viral STDs. Natural history of these infections in the vaginal xenograft model will be carried out as well as intervention studies with selected microbicides. Other model virus systems (for example, the rabbit oral papillomavirus) will also be used as surrogate systems. The four Project will focus on C. trachomatis infection and identification of effective microbicidal interventions as well as the consequences thereof for intracellular chlamydiae in already infected natural infections of C. trachomatis in a porcine model will be established and microbicides tested in this system.
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