Vaginal mAB Delivery Systems

阴道 mAB 输送系统

• 批准号: 8706778
• 负责人: Thomas Ray Moench
• 金额: $ 5.66万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 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/8706778
• 关键词: Adherence; Antibodies; Antiviral Agents; Categories; Cervical; Cervix Uteri; Clinical; Coitus; Complex; Data; Development; Devices; Diffusion; Dose; Effectiveness; Environment; Environmental Impact; Epithelium; Failure; Film; HIV; HIV/STD; Human; Immune system; Immunoglobulin G; In Vitro; Infection; Instruction; Mediating; Methods; Modification; Monoclonal Antibodies; Passive Immunization; Performance; Pharmaceutical Preparations; Production; Proteins; Resources; Safety; Simplexvirus; Surface; System; Technology; Tenofovir; Time; Vagina; Vaginal Diaphragm; Vaginal Gel; Vaginal Ring; base; cervicovaginal; cost; flexibility; improved; in vivo; microbicide; novel; pathogen; prevent; small molecule; vaginal microbicide

The recent successful trial of tenofovir vaginal gel provides important proof of concept indicating that a vaginal microbicide can prevent HIV. However, the limited protection observed (39% overall), argues for the development of additional microbicide agents and methods to deliver them. This IPCP application will develop a monoclonal antibody (Mab) based microbicide, distinct from the small molecule antiretrovirals that dominate the current microbicide pipeline. Mabs show promise in providing safe, potent, and specific, yet broad-spectrum microbicide action. Project 4 will attempt to enhance Mab effectiveness by its focus on the means of Mab delivery. Limitations on microbicide effectiveness can be divided into two categories: first, intrinsic failure of the method to provide protection when used ("method failure"); and second, failure to use the method consistently and correctly ("user failure"). We will attempt to reduce this second failure mode by developing three novel non-coital methods of microbicide delivery related by their emphasis on providing non-coital continuous dosing. Because these methods will not require action immediately in advance of coitus, we expect them to improve the proportion of coital acts wherein the microbicide is present. Moreover, we hypothesize an additional benefit: We believe inadequate distribution is responsible for many microbicide failures, and is responsible for the much higher concentrations of microbicide generally needed for in vivo protection compared to that required in vitro. We hypothesize that continuous or repeated dosing will improve microbicide distribution due to generous diffusion time for Mabs to cover the entire folded surface of the vagina. Our three Specific Aims will thus develop athe following three non-coital methods: SA1: Versaring, an intravaginal ring based on technology with proven clinical performance in sustained release of an antiviral, here to be adapted for sustained vaginal release of monoclonal antibodies; SA2: User-recharged Versaring, a modification of Versaring that will allow user replacement of Mab releasing units for production at lowest cost; SAS: Delivery of Mabs using the Duet® cervical barrier device.

替诺福韦阴道凝胶最近成功的试验提供了重要的概念证明，表明 阴道杀菌剂可以预防艾滋病毒。但是，观察到的有限保护（总体上为39％），主张 开发额外的菌心剂和交付它们的方法。此IPCP应用程序将 开发基于单克隆抗体（MAB）的菌糖，与小分子抗逆转录病毒不同 主导当前的菌心管道。 mabs在提供安全，潜力和具体的方面表现出希望 广谱菌心作用。项目4将尝试通过关注MAB的有效性来增强MAB的有效性 mab交付的手段。对杀菌剂有效性的局限性可以分为两类：首先， 使用时提供保护的方法的固有故障（“方法故障”）；其次，不使用 该方法一致，正确（“用户失败”）。我们将尝试通过减少第二个故障模式 开发三种新颖的非核心杀菌剂传递方法，它们的重点是提供 非金属连续剂量。因为这些方法将不需要立即采取行动 同性恋，我们希望它们能够改善存在菌心存在的同性行为的比例。而且， 我们假设一个额外的好处：我们认为分布不足是许多杀微生物的原因 失败，并导致体内通常需要较高浓度的菌心浓度 与体外所需的保护相比。我们假设连续或重复的给药将 由于mab的宽敞扩散时间覆盖了整个折叠表面，因此改善了菌心剂的分布 阴道。因此，我们的三个特定目标将开发以下三种非统一方法：SA1： Versaring是一种基于技术的腔内环，在持续释放的临床表现 抗病毒，在这里适应单克隆抗体的阴道释放； SA2：用户回报 Versaring是一种变式的修改，该修改将允许用户更换MAB释放单元进行生产 以最低的成本； SAS：使用Duet®子宫颈屏障设备传递mABS。