Comparative gynecology of Humans and Macaques

在世界范围内，超过80%的艾滋病毒感染是由于阴道传播。有一个 迫切需要一种安全有效的杀微生物剂，以防止艾滋病毒传播给妇女。 然而，筛选潜在杀微生物剂候选物的方法各不相同，包括细胞和组织培养 评估功效的实验和评估功效和安全性的非人灵长类动物模型。 然而，不同的实验室在细胞和器官培养物的类型方面存在差异 不同的实验室使用不同种类的非人灵长类动物。迄今为止，没有比较研究 有beijn。在“正常”人、雌性生殖组织和非人灵长类动物之间进行， 因此，目前尚不清楚在非人灵长类动物中进行的杀微生物剂研究是否能预测杀微生物剂的疗效， 女人的安全。此外，大多数用于评估基线水平的女性阴道外植研究 阴道免疫细胞，测试杀微生物剂候选物，以及体外艾滋病毒传播研究 无一例外地涉及使用来自阑尾切除术的组织，这些组织无一例外地是有病的。 因此，炎症、增生、溃疡或其他异常可能存在于这样的组织中， 影响杀微生物剂研究的结果。研究项目2的目标是进行比较研究 正常和子宫切除术衍生的女性阴道和宫颈组织与两种 猕猴（恒河猴和猪尾猴）比较免疫细胞的解剖学和免疫表型， 这些物种的雌性生殖组织之间的反应，以便更好地了解决策， 可以进行杀微生物剂测试。我们还将研究CCR 5抑制剂的作用机制， （RANTES类似物）在外植体模型中使用可光活化的病毒体和标记的RANTES类似物， 确定这些杀微生物剂候选物的阻断发生在何处。具体目标是： 具体目标1：比较正常猕猴和人类的解剖学、免疫学和生理学 使用相同方法的雌性生殖组织; 具体目标2：比较女性、恒河猴和猪尾猴宫颈外植体的免疫反应 猕猴对有丝分裂原，潜在的杀微生物剂候选物（RANTES类似物）和HIV/SIV使用相同的 方法论，以及; 具体目标3：评估合成RANTES的渗透深度和作用机制 衍生物和其它CCR 5抑制剂杀微生物剂候选物。

Project 2 Worldwide, over 80% of HIV infections occur as a result of vaginal transmission. There is a desperate need for a safe and effective microbicide than can prevent the transmission of HIV to women. However, methods for screening potential microbicide candidates vary and include cell and tissue culture experiments to assess efficacy and nonhuman primate models for assessing efficacy and safety. However, methods vary between different laboratories regarding the types of cells and organ cultures used, various laboratories use different species of nonhuman primates. To date, no comparative studies have beejn. performed between/'normal''human, .female reproductive tissues and nonhuman primates, Thus,-it4s.not known-whether-microbicide studies-in nonhuman primates will be predictive of efficacy and safety in women. Furthermore, most vaginal explant studies of women used for assessing baseline levels of immune cells in the vagina, testing microbicide candidates, and studies of HIV transmission in vitro have invariably involved the use of tissues derived from hysterectomies, which are invariably diseased. Thus, inflammation, hyperplasia, ulcerations or other abnormalities may exist in such tissues that could affect the results of microbicide studies. The goal of Research Project 2 is to perform comparative studies of normal and hysterectomy-derived vaginal and cervical tissues of women to those of two species of macaques (rhesus and pigtails) to compare the anatomy and immunophenotype of immune cells and responses between female reproductive tissues of these species so that better informed decisions for microbicide testing can be made. We will also investigate the mechanisms of action of CCR5 inhibitors (RANTES analogs) in explant models using photoactivateable virions and labeled RANTES analogs to determine where blocking of these microbicide candidates takes place. The specific aims are to: Specific Aim 1: Compare the anatomy, immunology, and physiology of normal macaque and human female reproductive tissues using identical methodology; Specific Aim 2: Compare the immune responses of cervical explants of women, rhesus, and pig-tailed macaques to mitogens, potential microbicide candidates (RANTES analogs), and HIV/SIV using identical methodology, and; Specific Aim 3: Assess the depth of penetration and mechanisms of action of synthetic RANTES derivatives, and other CCR5 inhibitor microbicide candidates in human and macaque vaginal tissues.