HIV Vaccines Clinical Trials Network Leadership and Operations Center

该提案概述了艾滋病毒疫苗试验领导和操作中心的科学议程 由内科科学家在4大洲15个国家和地区的临床试验基地合作建立的 致力于开发一种全球有效的艾滋病毒疫苗。在本供资期间，HVTN已 通过采用两种艾滋病毒疫苗概念和广泛中和的单抗改变了艾滋病毒预防科学 抗体(MAb)VRC01从1期到疗效评价。我们在亚洲区增加了超过35个临床试验点 在撒哈拉非洲，目前有12,500多名参与者参加了随机对照疗效试验。 我们建议继续保持我们在艾滋病毒疫苗领域的科学领导地位。疫苗的科学流水线与 诱导针对艾滋病毒的广谱中和抗体(BNAbs)的潜力已显著扩大。这项建议 描述了一个新的快速跟踪阶段1计划，以迭代的方式评估候选修剪分子、生殖系或 旨在诱导成人bNAb的血统疫苗。研究这些疫苗的第一阶段计划 还提出了接触HIV-1的婴儿。HVTN目前已经进行了五项艾滋病毒疗效试验。两种疫苗 试验(HVTN 702和705)正在进行中；第三个(HVTN 706)将于2019年8月开始；我们正在合作 与艾滋病毒预防试验网络(HPTN)一起对两项抗体介导的预防(AMP)试验进行评估 被动给药单抗的输注。这些疗效试验将确定中和和/或非 中和抗体，以防止艾滋病毒感染。疗效试验的样本和统计设计如下 围绕保护的相关性发展；我们将继续发展强大的综合实验室，统计 以及定义这些关联所需的计算平台。我们还将继续扩大我们的行为 科学计划，以加强我们已经成功的招聘和留住计划，并继续 扩大有色人种和变性人进入HVTN试验的范围。 疫苗临床试验涉及临床试验地点、HVTN实验室、计算 科学家以及我们的运营、培训、指导和财务管理团队；这些互动是 在应用程序中描述的。我们为艾滋病毒疫苗建立的临床、实验室和统计基础设施 还将用于协助结核病(TB)疫苗的开发。重要的是，我们将在我们成功的基础上 独特的以社区为基础的计划以及社区代表和社区咨询的整合 董事会参与了HVTN的研究过程和行为。我们还将继续开发下一代疫苗 并扩大我们的科学合作，以吸引科学界利用广泛的 我们已经建立了标本和数据仓库。本提案中的HVTN的总体目标是开发 一种疫苗方案或联合单抗方案，将减少成人和婴儿感染艾滋病毒的机会 超过60%。

This proposal outlines the scientific agenda of the Leadership and Operations Center of the HIV Vaccine Trials Network (HVTN), the collaboration of physician scientists at 64 clinical trial sites in 15 countries on 4 continents dedicated to developing a globally effective HIV vaccine. During the current funding period, the HVTN has transformed HIV prevention science by taking two HIV vaccine concepts and the broadly neutralizing monoclonal antibody (mAb) VRC01 from phase 1 to efficacy evaluation. We have added over 35 clinical trial sites in sub- Saharan Africa and now have over 12,500 participants enrolled in randomized controlled efficacy trials. We propose to continue our scientific leadership in HIV vaccines. The scientific pipeline for vaccines with the potential to induce broadly neutralizing antibodies (bnAbs) to HIV has markedly expanded. This proposal describes a novel fast-track phase 1 program to assess, in an iterative fashion, candidate trimers, germline or lineage-based vaccines designed to elicit bnAbs in adults. A phase 1 program to investigate these vaccines in HIV-1–exposed infants is also proposed. The HVTN currently has five HIV efficacy trials in place. Two vaccine trials (HVTN 702 & 705) are in progress; a third (HVTN 706) will start in August 2019; and we are collaborating with the HIV Prevention Trials Network (HPTN) on two antibody-mediated prevention (AMP) trials evaluating the infusion of passively administered mAbs. These efficacy trials will define the potential of neutralizing and/or non- neutralizing antibodies to prevent HIV acquisition. The samples and statistical design of the efficacy trials are developed around correlates of protection; we will continue to develop the robust integrated laboratory, statistical and computational platform needed to define these correlates. We will also continue to expand our behavioral sciences program to enhance our already successful recruitment and retention programs, and to continue to expand the enrollment of persons of color and transgender persons into HVTN trials. Vaccine clinical trials involve a complex interplay between clinical trial sites, HVTN laboratories, computational scientists, and our operational, training, mentoring, and fiscal management teams; these interactions are described in the application. The clinical, laboratory and statistical infrastructure we have built for HIV vaccines will also be used to assist in tuberculosis (TB) vaccine development. Importantly, we will build on our success in the unique community-based programs and integration of community representatives and community advisory boards into HVTN research process and conduct. We will also continue to develop the next generation of vaccine scientists and expand our scientific collaborations to engage the scientific community to utilize the extensive specimen and data repositories we have established. The overall goal of the HVTN in this proposal is to develop a vaccine regimen or combination mAb regimen that will reduce HIV acquisition in adults and infants by more than 60 percent.