Comparative gynecology of Humans and Macaques

项目2在全球范围内，超过80%的艾滋病毒感染是由阴道传播造成的。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，筛选潜在杀菌剂候选者的方法各不相同，包括细胞培养和组织培养 评估疗效的实验和评估疗效和安全性的非人类灵长类动物模型。 然而，不同的实验室对细胞和器官培养的类型有不同的方法。 不同的实验室使用不同种类的非人类灵长类动物。到目前为止，还没有进行比较研究 吃点东西吧。在正常的人类、雌性生殖组织和非人灵长类之间进行， 因此，在非人类灵长类动物中是否进行杀微生物剂研究将预测疗效和 女性的安全。此外，大多数对女性的阴道外植体研究都用于评估基线水平 阴道中免疫细胞的研究，杀微生物剂候选的测试，以及艾滋病毒体外传播的研究 总是涉及子宫切除手术的组织的使用，而子宫切除术总是有病变的。 因此，这种组织中可能存在炎症、增生、溃疡或其他异常，这些组织可能 影响杀微生物剂的研究结果。研究项目2的目标是进行比较研究 正常和子宫切除术后妇女的阴道和宫颈组织对两种 猕猴(恒河猴和辫子)比较免疫细胞和免疫表型的解剖和表型 这些物种的雌性生殖组织之间的反应，以便更好地做出明智的决定 可以进行杀微生物剂测试。我们还将研究CCR5抑制剂的作用机制。 (RANTES类似物)在使用光激活病毒粒子和标记的RANTES类似物的外植体模型中 确定阻止这些杀微生物剂候选的地点。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 使用相同方法的女性生殖组织； 特定目标2：比较女性、恒河猴和猪尾宫颈移植的免疫应答 猕猴对有丝分裂原、潜在的杀微生物剂候选物(RANTES类似物)和艾滋病毒/SIV使用相同的 方法论； 具体目标3：评估合成RANTES的渗透深度和作用机制 衍生物和其他CCR5抑制剂杀微生物剂候选在人类和猕猴阴道组织中。

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.