Laboratory Core

这项IP/CP授予的微生物学/病毒学核心B是“替诺福韦和UC781的替代制剂” 完全融入该提案，为所有4个项目提供支持和互动。这个核心带来了 抗逆转录病毒(ARV)药物、赋形剂和 配方。微生物学/病毒学核心B将通过筛选赋形剂来支持配方项目1 和配方膜，以确保它们不会对代表正常阴道的乳杆菌起作用 并筛查性传播病原体(STP)的赋形剂活性。正常的阴道 众所周知，菌群在预防艾滋病毒-1和其他性传播疾病感染方面很重要。这一核心将提供 使用宫颈外植体和上皮单层培养对配方ARV安全性的标准化测试 为支持项目1、2、3和4。将使用 支持项目2、3和4的宫颈外植体培养，同时指导项目1的配方。 将使用体外活组织来支持动物和人类试验，以证明对SHV/HIV-1的保护 感染(支持所有项目)。项目2和项目3中使用的薄膜和凝胶制剂的效果将是 通过核心的培养工作来监测微生物区系。在项目3中，这个核心将筛选主题 对于STP和正常菌群，以确保受试者符合纳入标准。宫颈阴道灌洗液(CVL) 样本将在项目2、3和4中收集，并用于药代动力学研究。此核心将利用这些 CVL通过检查来确定该和/或制剂是否干扰天然免疫过程 安慰剂和含药薄膜和凝胶对杀灭HIV-1、HSV和细菌的影响。另外， 阴道液中含有杀死单纯疱疹病毒和一些细菌的已知因素。一种有效的杀菌剂不能 干扰这些过程，同时使HIV-1失活或防止其感染。总体而言，这 IP/CP寻求开发一种安全地预防HIV-1感染而不干扰正常菌群或 其他天然防御和这一核心将确保成功的杀微生物剂候选为进一步 临床评价。

The Microbiology/Virology Core B of this IP/CP Grant "Alternative Formulations of Tenofovir and UC781" is fully integrated into this proposal providing support and interactions with all 4 projects. This Core brings several new innovations to the safety and efficacy testing of antiretroviral (ARVs) drugs, excipients, and formulations. Microbiology/Virology Core B will support the Formulations Project 1 by screening excipients and formulated films to ensure they are not active against Lactobacillus representative of normal vaginal flora and to screen for excipient activity against sexually transmitted pathogens (STPs). The normal vaginal flora is known to be important in the prevention of infection by HIV-1 and other STPs. This Core will provide standardized testing of formulated ARV safety using ecto-cervical explant and epithelial monolayer cultures in support of Projects 1, 2, 3 and 4. ARV film efficacy and coital timing testing will be performed using the ecto-cervical explant cultures supporting Projects 2, 3, and 4 while guiding formulations in Project 1. Core B will support the animal and human trials using ex vivo biopsies to demonstrate protection from SHIV/HIV-1 infection (supporting all projects). The effects of films and gel preparation used in Projects 2 and 3 will be monitored by culture work in the Core to monitor the microflora. In Project 3, this Core will screen subjects for STPs and normal floras to assure subjects meet inclusion criterion. Cervicovaginal lavages (CVLs) samples will be collected in Projects 2, 3 and 4 and for pharmacokinetic study. This Core will utilize those CVL to determine if the and/or formulation interfere with the natural innate immunity process by examining the effects of placebo and drug containing films and gels on the killing of HIV-1, HSV, and bacteria. Also, vaginal fluid contains factors known to kill HSV as well as some bacteria. An effective microbicide can not interfere with these processes and at the same time inactivate HIV-1 or prevent its' infection. Overall, this IP/CP seeks to develop a product which prevents HIV-1 infection safely without disturbing the normal flora or other natural defenses and this Core will ensure a successful microbicide candidate is created for further clinical evaluation.