LAB/CV-N AND RC101 PRIMATE TESTING

LAB/CV-N 和 RC101 灵长类动物测试

• 批准号: 7310322
• 负责人: DOROTHY L PATTON
• 金额: $ 25.22万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7310322
• 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.

开发局部杀菌剂用于预防包括艾滋病毒在内的性传播感染的局部杀菌剂的研究工作已经持续了近十年。根据世界卫生组织的数据，估计有3.33亿个新的阴道和直肠传播疾病的新病例发生。显然，理想的菌心可以防止阴道和直肠获得性传播感染（STI）的传播。因此，必须测试局部杀菌剂产品，以确保防止HIV和其他性传播感染的性传播，并保留阴道和直肠环境，包括上皮。我们已经开发了一个有用的模型，以评估阴道和直肠瘤中的局部杀菌剂产品的安全性。我们已经使用该模型来研究菌皮剂对阴道和直肠微生物和上皮细胞的单一和重复应用的影响。这种猕猴模型的优势之一是辫子和人类共享的类似的阴道菌群。尤其是内源性乳酸乳杆菌，尤其是产生H2O2的乳酸杆菌， 提供了确定产品对阴道微生物学的影响的研究，更重要的是阴道环境中H2O2的产生，该阴道环境具有抗菌特性。该项目的具体目的是记录猕猴模型中优化的乳杆菌产物的定植和蓝氧病毒分泌。此外，我们将使用猕猴模型来评估该程序中开发的阴道和直肠应用产品的安全性。这些猕猴的研究将提供重要的临床前数据，以将程序的局部菌心产品推进I期临床试验。