LAB/CV-N AND RC101 PRIMATE TESTING

LAB/CV-N 和 RC101 灵长类动物测试

• 批准号: 6955870
• 负责人: DOROTHY L PATTON
• 金额: $ 14.37万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-01 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6955870
• 关键词: AIDS education /prevention; Lactobacillus; Macaca nemestrina; antiAIDS agent; biological models; drug screening /evaluation; hydrogen peroxide; local antiinfective agents; microorganism growth; mucosa; rectum /anus; sexually transmitted diseases; topical drug application; vagina

Research efforts to develop topical microbicides for intravaginal use for prevention of sexually transmitted infections including HIV have been ongoing for nearly a decade. An estimated 333 million new cases of vaginally and rectally transmitted diseases occur in the world each year according to the World Health Organization. Clearly, an ideal microbicide would prevent the transmission of both vaginally and rectally acquired sexually transmitted infections (STI). Therefore, topical microbicide products must be tested to ensure that the sexual transmission of HIV and other sexually transmitted infections is prevented, and that the vaginal and rectal environments, including the epithelium, are preserved. We have developed a useful model to evaluate the safety of topical microbicide products after vaginal and rectal use in the pigtailed macaque. We have used this model to study the effects of single and repeated applications of microbicides on vaginal and rectal microflora and epithelium. One of the strengths of this macaque model is the similar vaginal microflora shared by the pigtailed macaque and humans. The presence of endogenous lactobacilli, and of H2O2-producing lactobacilli in particular, provides for studies which determine a product's influence on vaginal microbiology and more importantly on the production of H2O2 in the vaginal milieu, which is known to have antimicrobial properties. The specific aims of this project are to document the colonization and cyanovirin secretion of an optimized lactobacillus product in the macaque model. Additionally, we will use the macaque model to assess the safety of vaginally and rectally applied products developed in this Program. These macaque studies will provide important preclinical data for advancing the Program's topical microbicide product to phase I clinical trials.

开发用于阴道内使用的局部杀菌剂以预防包括艾滋病毒在内的性传播感染的研究工作已经持续了近十年。据世界卫生组织估计，全球每年会出现 3.33 亿新的阴道和直肠传播疾病病例。显然，理想的杀菌剂能够防止阴道和直肠获得性传播感染 (STI) 的传播。因此，必须对外用杀菌剂产品进行测试，以确保预防艾滋病毒和其他性传播感染的性传播，并保护阴道和直肠环境，包括上皮。我们开发了一个有用的模型来评估猪尾猕猴阴道和直肠使用外用杀菌剂产品的安全性。我们使用该模型来研究单次和重复使用杀菌剂对阴道和直肠微生物区系和上皮的影响。该猕猴模型的优点之一是辫子猕猴和人类具有相似的阴道微生物群。内源性乳杆菌，特别是产生 H2O2 的乳杆菌的存在， 提供了确定产品对阴道微生物学的影响的研究，更重要的是对阴道环境中 H2O2 产生的影响，众所周知，H2O2 具有抗菌特性。该项目的具体目标是记录优化的乳杆菌产品在猕猴模型中的定植和氰基病毒蛋白分泌。此外，我们将使用猕猴模型来评估本计划中开发的阴道和直肠应用产品的安全性。这些猕猴研究将为将该计划的外用杀菌剂产品推进一期临床试验提供重要的临床前数据。