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运营中心的科学议程 HVTN是由4大洲15个国家的64个临床试验中心的医生科学家合作建立的 致力于开发全球有效的艾滋病毒疫苗。在目前的资助期间，HVTN已 通过采用两种艾滋病毒疫苗概念和广泛中和的单克隆抗体， 抗体（mAb）VRC 01从I期至疗效评价。我们已经增加了超过35个临床试验地点， 撒哈拉非洲，现在有超过12，500名参与者参加了随机对照疗效试验。 我们提议继续在艾滋病毒疫苗方面发挥科学领导作用。疫苗的科学管道， 诱导针对HIV的广泛中和抗体（bnAb）的潜力已经显著扩大。这项建议 描述了一种新的快速通道1期程序，以迭代方式评估候选三聚体、种系或 设计用于在成人中引发bnAb的谱系疫苗。一个研究这些疫苗的第一阶段计划， 还提出了暴露于HIV-1的婴儿。HVTN目前有五项艾滋病毒疗效试验。两个疫苗 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）合作进行两项抗体介导的预防（AMP）试验， 输注被动施用的mAb。这些有效性试验将确定中和和/或非中和的可能性。 中和抗体，以防止艾滋病毒感染。有效性试验的样本和统计设计如下： 围绕保护相关因素开发;我们将继续开发强大的综合实验室， 和计算平台来定义这些关联。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保留计划，并继续 扩大HVTN试验中有色人种和变性人的入组。 疫苗临床试验涉及临床试验地点、HVTN实验室、计算机和计算机之间的复杂相互作用。 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。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疫苗的开发。重要的是，我们将在成功的基础上， 独特的以社区为基础的方案以及社区代表和社区咨询的整合 董事会进入HVTN研究过程和行为。我们还将继续研发下一代疫苗 科学家和扩大我们的科学合作，使科学界利用广泛的 我们建立的标本和数据库。本提案中HVTN的总体目标是开发 一种疫苗方案或联合mAb方案，将使成人和婴儿的HIV感染率降低更多 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.