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

• 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
• 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

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.

这份提案概述了艾滋病毒疫苗领导和运营中心的科学议程 由在15个国家和地区的临床试验地点合作的临床试验网络(HVTN)于4月4日 各大洲致力于开发针对艾滋病毒、结核病和现在的SARS-CoV-2的全球有效疫苗。 20多年来，HVTN一直领导艾滋病毒预防科学，一直处于强健的1期和2期临床阶段 开发试验，目前有2种载体疫苗(ALVAC和AD26)和1种广泛中和疫苗 进行5项随机对照疗效试验的单抗VRC01。 随着新冠肺炎大流行的迅速爆发，我们认识到在 免疫功能在预防感染、治疗新冠肺炎疾病、 在清除病毒感染方面。我们相信，HVTN处于有利地位，可以研究这些差距并迅速部署 SARS-CoV-2中和疫苗和单抗治疗发展方面的信息。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 2个地点)和秘鲁(5个地点)从SARS-CoV-2感染中康复。参与者将从各种不同的人中招募 危险群体和临床队列：住院与非住院、有症状与无症状的成人 年龄在18至55岁之间和55岁以上的人，以及对临床或 病毒学表现(例如，发生心肌炎/心包炎，需要插管的人，延长 病毒脱落，或在最初清除感染后出现阳性病毒学测试的人)。的具体目标 这项研究包括识别区分SARS-CoV-2感染和疫苗接种的血清学反应，以 开发和鉴定一套免疫学分析和参考试剂，以使详细的 检测SARS-CoV-2感染后免疫应答的研究 研究人群和风险群体，并描述康复期个人感染的特征。 这项初步研究将告诉我们许多关于感染者的获得性免疫反应。 并从SARS-CoV-2中康复，将阐明免疫系统在成功地 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标志，并将告知合理的设计和检测预防性 以及治疗性疫苗和单抗。此外，该协议还将为 对这种感染进行前瞻性研究，更好地确定关键风险群体和知识差距。最后，这项研究将 为目前进入临床试验流水线的大量新冠肺炎疫苗做好网络准备。 实验室、统计和操作经验将是这一首次试验的宝贵准备和准备工作 作为联合NIAID COVID的一部分，HVTN准备推出几项疗效试验 未来几个月的预防网络。