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.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Program Projects (P01)
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Special Emphasis Panel (ZAI1-ALR-M (M4))
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Savarese, Barbara M
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Drexel University
Schools of Arts and Sciences
United States
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Passic, Shendra R; Ferguson, Mary Lee; Catalone, Bradley J et al. (2010) Structure-activity relationships of polybiguanides with activity against human immunodeficiency virus type 1. Biomed Pharmacother 64:723-32
Pavlovic, Jelena; Floros, Joanna; Phelps, David S et al. (2008) Differentiation of xenografted human fetal lung parenchyma. Early Hum Dev 84:181-93
Beer, Brigitte E; Doncel, Gustavo F; Krebs, Fred C et al. (2006) In vitro preclinical testing of nonoxynol-9 as potential anti-human immunodeficiency virus microbicide: a retrospective analysis of results from five laboratories. Antimicrob Agents Chemother 50:713-23
Fang, L; Meyers, C; Budgeon, L R et al. (2006) Induction of productive human papillomavirus type 11 life cycle in epithelial cells grown in organotypic raft cultures. Virology 347:28-35
Hartmann, Sandra Urdaneta; Wigdahl, Brian; Neely, Elizabeth B et al. (2006) Biochemical analysis of human milk treated with sodium dodecyl sulfate, an alkyl sulfate microbicide that inactivates human immunodeficiency virus type 1. J Hum Lact 22:61-74
Deka, Srilekha; Vanover, Jennifer; Dessus-Babus, Sophie et al. (2006) Chlamydia trachomatis enters a viable but non-cultivable (persistent) state within herpes simplex virus type 2 (HSV-2) co-infected host cells. Cell Microbiol 8:149-62
Hartmann, Sandra Urdaneta; Berlin, Cheston M; Howett, Mary K (2006) Alternative modified infant-feeding practices to prevent postnatal transmission of human immunodeficiency virus type 1 through breast milk: past, present, and future. J Hum Lact 22:75-88; quiz 89-93
Fang, L; Budgeon, L R; Doorbar, J et al. (2006) The human papillomavirus type 11 E1/E4 protein is not essential for viral genome amplification. Virology 351:271-9
Urdaneta, Sandra; Wigdahl, Brian; Neely, Elizabeth B et al. (2005) Inactivation of HIV-1 in breast milk by treatment with the alkyl sulfate microbicide sodium dodecyl sulfate (SDS). Retrovirology 2:28
Krebs, Fred C; Miller, Shendra R; Ferguson, Mary Lee et al. (2005) Polybiguanides, particularly polyethylene hexamethylene biguanide, have activity against human immunodeficiency virus type 1. Biomed Pharmacother 59:438-45

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