HIV Vaccines Clinical Trials Network Leadership and Operations Center

HIV 疫苗临床试验网络领导和运营中心

• 批准号: 10311601
• 负责人: Dan H. Barouch
• 金额: $ 4312.46万
• 依托单位: FRED HUTCHINSON CANCER RESEARCH CENTER
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-15 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10311601
• 关键词: AIDS clinical trial group; AIDS prevention; Adherence; Adjuvant; Adult; Affect; Africa South of the Sahara; Aftercare; Animal Model; Antibodies; Antibody titer measurement; Antibody-mediated protection; Antigens; B-Lymphocytes; Behavior; Behavioral Sciences; Binding; Biological Specimen Banks; Cell Lineage; Child; Childhood; Clinical; Clinical Trials; Clinical Trials Network; Collaborations; Color; Combined Vaccines; Communities; Community Integration; Complex; Consensus; Country; Disease; Effectiveness; Enrollment; Epidemiology; Epitopes; Event; Feedback; Funding; Genetic; Genotype; Goals; HIV; HIV Infections; HIV Vaccine Trials Network; HIV prevention trials network; HIV vaccine; HIV-1; Human Milk; Immune; Immune response; Immunization; Immunologics; Individual; Infant; Infection; Infection prevention; Infrastructure; Infusion procedures; Injections; Integration Host Factors; International Maternal Pediatric Adolescent AIDS Clinical Trials; Laboratories; Leadership; Licensure; Mediating; Medicine; Mentors; Microbiology; Monoclonal Antibodies; Morbidity - disease rate; Outcome; Participant; Passive Immunization; Persons; Phase; Phase I Clinical Trials; Phenotype; Physicians; Placebos; Population; Populations at Risk; Prevention trial; Process; Protocols documentation; Randomized; Recurrence; Regimen; Research; Research Personnel; Risk; Safety; Sampling; Science; Scientist; Severities; Site; Societal Factors; Surrogate Markers; System; T-Lymphocyte; Testing; Training; Treatment Failure; Treatment outcome; Tuberculosis; Tuberculosis Vaccines; Vaccination; Vaccine Clinical Trial; Vaccine Design; Vaccine Research; Vaccines; Virus; Work; age group; antiretroviral therapy; base; behavioral/social science; clinical development; community engagement; computational platform; data repository; design; diagnostic technologies; efficacy evaluation; efficacy testing; efficacy trial; immunogenicity; infant infection; insight; mortality; neutralizing antibody; neutralizing monoclonal antibodies; nonhuman primate; novel; novel vaccines; operation; pandemic disease; participant retention; phase II trial; population based; pre-clinical; pressure; prevent; programs; recruit; success; transgender; transmission process; tuberculosis treatment; vaccine acceptance; vaccine candidate; vaccine development; vaccine trial; vaccine-induced antibodies

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.

该提案概述了HIV疫苗试验领导和运营中心的科学议程 Network（HVTN），在4大洲15个国家的64个临床试验地点的物理科学家的合作 致力于开发全球有效的HIV疫苗。在当前的资金期间，HVTN具有 通过采用两种HIV疫苗概念和广泛中和的单克隆来改变HIV预防科学 从第1阶段到效率评估的抗体（MAB）VRC01。我们已经在子 - 撒哈拉非洲和现在有12,500多名参与者参加了随机对照效率试验。 我们建议继续我们在艾滋病毒疫苗方面的科学领导。疫苗的科学管道 向HIV诱导广泛中和抗体（BNAB）的潜力显着扩大。这个建议 描述了一个新颖的快速轨道第一阶段计划，以迭代方式，候选三聚体，种系或 基于谱系的疫苗旨在引起成人的BNAB。一项1阶段计划，以调查这些疫苗 还提出了HIV-1暴露的婴儿。 HVTN目前有五项HIV效率试验。两种疫苗 正在进行试验（HVTN 702和705）；第三个（HVTN 706）将于2019年8月开始；我们正在合作 通过两种抗体介导的预防（AMP）试验，HIV预防试验网络（HPTN）评估了 注入被动施用的mAb。这些有效的试验将定义中和的潜力 中和抗体，以防止艾滋病毒获取。效率试验的样本和统计设计是 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 定义这些相关性所需的计算平台。我们还将继续扩大我们的行为 科学计划，以增强我们已经成功的招聘和保留计划，并继续 将有色人种和变性人的人的入学率扩展到HVTN试验中。 疫苗临床试验涉及临床试验地点，HVTN实验室，计算的复杂相互作用 科学家以及我们的运营，培训，心理和财政管理团队；这些相互作用是 在应用程序中描述。我们为HIV疫苗建造的临床，实验室和统计基础设施 还将用于协助结核病（TB）疫苗发育。重要的是，我们将以我们的成功为基础 独特的基于社区的计划以及社区的整合代表和社区咨询 董事会进入HVTN研究过程和行为。我们还将继续开发下一代疫苗 科学家并扩大我们的科学合作，以吸引科学界利用广泛的 我们已经建立的标本和数据存储库。 HVTN在本提案中的总体目标是发展 一种疫苗方案或组合MAB方案，该方案将减少成人和婴儿的HIV获取 超过60％。