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.

该提案概述了艾滋病毒疫苗试验领导和运营中心的科学议程 网络 (HVTN)，由 4 大洲 15 个国家的 64 个临床试验中心的医师科学家合作组成 HVTN 致力于开发全球有效的艾滋病毒疫苗。 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，改变了艾滋病毒预防科学 抗体（mAb）VRC01从1期到疗效评估我们已经在亚组中增加了超过35个临床试验点。 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。 我们建议继续保持我们在艾滋病毒疫苗领域的科学领先地位。 诱导艾滋病毒广泛中和抗体（bnAbs）的潜力已显着扩大。 描述了一种新颖的快速通道第一阶段计划，以迭代方式评估候选三聚体、种系或 旨在在成人中引发 bnAb 的基于谱系的疫苗 旨在研究这些疫苗的第一阶段计划。 还提议暴露于 HIV-1 的婴儿目前正在进行五项 HIV 功效试验。 试验（HVTN 702 和 705）正在进行中；第三个试验（HVTN 706）将于 2019 年 8 月开始，我们正在合作； 与 HIV 预防试验网络 (HPTN) 合作开展两项抗体介导预防 (AMP) 试验，评估 被动施用单克隆抗体的输注这些功效试验将确定中和和/或非单克隆抗体的潜力。 功效试验的样本和统计设计如下。 围绕保护相关性进行开发；我们将继续开发强大的综合实验室、统计 和定义这些关联所需的计算平台我们还将继续扩展我们的行为。 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 试验的有色人种和变性人的招募范围。 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； 申请中描述了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，我们将在我们的成功基础上再接再厉。 独特的基于社区的计划以及社区代表和社区咨询的整合 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，让科学界利用广泛的 本提案中 HVTN 的总体目标是开发样本和数据存储库。 疫苗方案或组合单克隆抗体方案可减少成人和婴儿感染艾滋病毒的几率 超过 60%。