HVTN 405/HPTN 1901 Characterizing SARS-CoV-2-specific immunity in convalescent individuals: LC

HVTN 405/HPTN 1901 表征恢复期个体的 SARS-CoV-2 特异性免疫力：LC

基本信息

批准号：
10165321
负责人：
Margaret Juliana McElrath
金额：
$ 2995.23万
依托单位：
FRED HUTCHINSON CANCER RESEARCH CENTER
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-06-24 至 2022-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10165321
关键词：
2019-nCoV AIDS prevention ALVAC Acute Adult Age-Years Biological Assay Biometry COVID-19 COVID-19 pandemic COVID-19 vaccine Cells Cellular Assay Chronic Clinical Clinical Trials Cohort Studies Collaborations Communicable Diseases Country Development Disease Disease Outbreaks Epitopes Eye Future Goals HIV Vaccine Trials Network HIV vaccine HIV/TB Health Immune Immune response Immune system Immunity Immunologic Markers Immunologics Immunology Immunology procedure Immunotherapeutic agent Individual Infection Infection Control Infection prevention Inflammation Intubation Joints Knowledge Laboratories Lead Leadership Light Malaria Measures Mediating Medical Medical History Monoclonal Antibodies Monoclonal Antibody Therapy Morbidity - disease rate Myocarditis National Institute of Allergy and Infectious Disease Participant Pathologic Pericarditis Persons Peru Pharmaceutical Preparations Phase Physicians Play Population Preparation Prevention Preventive vaccine Prospective Studies Protocols documentation Quality Control Randomized Randomized Clinical Trials Reagent Research Methodology Risk Role Sampling Science Scientist Series Serological Severity of illness Site Specificity System Testing Typhoid Fever United States Vaccination Vaccines Validation Virus Virus Diseases Virus Shedding adaptive immune response clinical development clinical trial analysis cohort coronavirus disease design efficacy study efficacy trial experience illness length immune function improved interest mortality neutralizing monoclonal antibodies neutralizing vaccine operation pandemic disease prevent programs quality assurance recruit response therapeutic vaccine vaccine trial vector-based vaccine virology

项目摘要

This proposal outlines the scientific agenda for 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 globally effective vaccines for HIV, tuberculosis and now SARS-CoV-2. The HVTN has led HIV prevention science for over 20 years through robust phase 1 and 2 clinical development trials and currently has 2 vector based vaccines (ALVAC and Ad26) and 1 broadly neutralizing monoclonal antibody (mAb) VRC01 undergoing testing in 5 randomized controlled efficacy trials. With the rapid onset of the COVID-19 pandemic, we recognize there is a significant gap in knowledge in the field on the contribution of immune functions involved in preventing infection, in modifying COVID-19 disease, and in clearing viral infection. We believe the HVTN is well placed to study these gaps and rapidly deploy this information in the development of SARS-CoV-2 neutralizing vaccines and mAb therapies. In this study we propose initiating an observational cohort study of approximately 400 persons in the United States (22 trials sites) and Peru (5 sites) convalescing from SARS-CoV-2 infection. Participants will be recruited from a variety of risk groups and clinical cohorts: hospitalized vs. non-hospitalized, symptomatic vs. asymptomatic, adults between 18 and 55 years of age and those older than 55 years, and persons with high interest clinical or virologic presentations (eg, persons who developed myocarditis/pericarditis, required intubation, had prolonged viral shedding, or who develop a positive virologic test after initially clearing the infection). Specific aims of this study include identifying serologic reactivities that differentiate SARS-CoV-2 infection from vaccination, to develop and qualify a suite of immunologic assays and reference reagents that will permit detailed interrogations of the immune response to infection, to measure SARS-CoV-2 adaptive response in key populations and risk groups, and to characterize presentations of the infection among convalescent individuals. This initial study will tell us much about the adaptive immune responses in persons who have been infected and recovered from SARS-CoV-2 and will shed light on the role the immune system plays in successfully clearance of infection. It will improve our understanding of the dynamics and duration of responses, as well as the epitope specificity and other defining signatures, and will inform rational design and testing of preventive and therapeutic vaccines and monoclonal antibodies. In addition, this protocol will lay the groundwork for prospective studies of this infection, better defining key risk groups and knowledge gaps. Lastly, this study will prepare the network for the large number of COVID-19 vaccines now entering the clinical trial pipeline. Laboratory, statistical and operational experience in this first trial will be invaluable preparation and priming of network machinery as the HVTN prepare to roll-out several efficacy trials as part of the joint NIAID COVID Prevention Network in coming months.

该提案概述了艾滋病毒疫苗领导和运营中心的科学议程试验网络 (HVTN)，由 15 个国家的 64 个临床试验中心的医师科学家于 4 月 4 日合作组成各大洲致力于开发全球有效的艾滋病毒、结核病和现在的 SARS-CoV-2 疫苗。 HVTN 通过稳健的 1 期和 2 期临床研究引领 HIV 预防科学 20 多年开发试验，目前有 2 种基于载体的疫苗（ALVAC 和 Ad26）和 1 种广泛中和疫苗单克隆抗体 (mAb) VRC01 正在 5 项随机对照功效试验中进行测试。随着 COVID-19 大流行的迅速爆发，我们认识到在相关知识方面存在巨大差距免疫功能在预防感染、改变 COVID-19 疾病方面的贡献领域，并清除病毒感染。我们相信 HVTN 完全有能力研究这些差距并迅速部署这一技术开发 SARS-CoV-2 中和疫苗和 mAb 疗法的信息。在这项研究中我们建议在美国启动一项约 400 人的观察性队列研究（22 项试验站点）和秘鲁（5 个站点）从 SARS-CoV-2 感染中恢复过来。参与者将从各个方面招募风险群体和临床队列：住院与非住院、有症状与无症状、成人 18岁至55岁之间以及55岁以上的人，以及对临床或临床有浓厚兴趣的人病毒学表现（例如，出现心肌炎/心包炎、需要插管、长期住院的人）病毒脱落，或最初清除感染后病毒学检测呈阳性）。具体目标这项研究包括确定区分 SARS-CoV-2 感染和疫苗接种的血清学反应，开发并鉴定一套免疫测定和参考试剂，以允许详细的询问对感染的免疫反应，以测量关键的 SARS-CoV-2 适应性反应人群和危险人群，并描述康复者中感染的表现。这项初步研究将告诉我们很多有关感染者的适应性免疫反应的信息并从 SARS-CoV-2 中恢复，并将揭示免疫系统在成功地发挥作用清除感染。它将提高我们对反应的动态和持续时间的理解，以及表位特异性和其他定义特征，并将为预防性药物的合理设计和测试提供信息以及治疗性疫苗和单克隆抗体。此外，该协议将为对这种感染的前瞻性研究，更好地确定关键风险群体和知识差距。最后，本研究将为目前进入临床试验渠道的大量 COVID-19 疫苗做好网络准备。第一次试验中的实验室、统计和操作经验将是宝贵的准备和启动作为 NIAID 新冠联合研究的一部分，HVTN 准备推出多项功效试验未来几个月的预防网络。