IDENTIFICATION AND PRECLINICAL TESTING OF MICROBICIDES FOR HPV

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Anogenital Human Papillomaviruses (HPVs) are the most common sexually transmitted pathogen and the primary cause of cervical cancer. A nonhuman model of PV infection using Rhesus papillomavirus (RhPV1) was recently developed at TNPRC through a pilot project. We were able to confirm infection of 5 of 5 rhesus with indications of progression to precancerous lesions, typical of HPV. The R21 Phase of this grant screened a database of 4.5 million small molecules, and have identified several candidate HPV-specific microbicides for testing. To begin the R33 phase of this proposal with studies in a nonhuman primate model for anogenital HPV infection, we conducted both serological and molecular screening of 25 female Rhesus macaques to assess prior exposure to RhPV1 and have identified 12 seronegative females that will go forward for the study. We have also developed a large stock of the challenge virus to be used for the proposed inoculations and await testing of our candidate microbicide compounds for reduction or arrest of viremia and progression of RhPV1 anogenital papillomavirus infections in the nonhuman primate.