IDENTIFICATION AND PRECLINICAL TESTING OF MICROBICIDES FOR HPV

HPV 杀菌剂的鉴定和临床前测试

• 批准号: 8358113
• 负责人: VICKI L TRAINA-DORGE
• 金额: $ 3.72万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8358113
• 关键词: Anogenital Human Papilloma Virus Infection; Databases; Exposure to; Female; Funding; Grant; Human Papillomavirus; Infection; Lesion; Macaca mulatta; Malignant neoplasm of cervix uteri; Modeling; Molecular; National Center for Research Resources; Papillomavirus; Papillomavirus Infections; Phase; Pilot Projects; Preclinical Testing; Premalignant; Primates; Principal Investigator; Research; Research Infrastructure; Resources; Screening procedure; Serological; Source; Testing; United States National Institutes of Health; Viremia; Virus; cost; microbicide; nonhuman primate; pathogen; small molecule

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.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的主要研究者可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 肛门生殖器人乳头瘤病毒 (HPV) 是最常见的性传播病原体，也是宫颈癌的主要原因。 TNPRC 最近通过一个试点项目开发了一种使用恒河猴乳头瘤病毒 (RhPV1) 的非人类 PV 感染模型。我们能够确认 5 只恒河猴中有 5 只受到感染，并有进展为癌前病变（典型的 HPV）的迹象。该资助的 R21 阶段筛选了包含 450 万个小分子的数据库，并确定了几种候选 HPV 特异性杀菌剂进行测试。 为了开始该提案的 R33 阶段，在非人类灵长类动物模型中进行肛门生殖器 HPV 感染研究，我们对 25 只雌性恒河猴进行了血清学和分子筛查，以评估之前接触 RhPV1 的情况，并确定了 12 只血清阴性雌性将继续进行这项研究。我们还开发了大量的挑战病毒用于拟议的接种，并等待对我们的候选杀微生物剂化合物进行测试，以减少或阻止非人类灵长类动物中的病毒血症和RhPV1肛门生殖器乳头瘤病毒感染的进展。