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

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），15个国家64个临床试验中心的医生科学家合作， 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通过强大的1期和2期临床试验，引领艾滋病预防科学20多年 目前有2种基于载体的疫苗（ALVAC和Ad 26）和1种广泛中和的疫苗。 单克隆抗体（mAb）VRC 01在5项随机对照疗效试验中进行测试。 随着COVID-19大流行的迅速爆发，我们认识到， 关于免疫功能在预防感染、改变COVID-19疾病、 以及清除病毒感染。我们相信HVTN能够很好地研究这些差距并迅速部署 在SARS-CoV-2中和疫苗和mAb疗法的开发中提供信息。本研究 我建议在美国启动一项约400人的观察性队列研究（22项试验 地点）和秘鲁（5个地点）从SARS-CoV-2感染中恢复。参与者将从各种各样的人中招募 风险组和临床队列：住院与非住院、有症状与无症状、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、 病毒脱落，或在最初清除感染后病毒学试验呈阳性的患者）。具体目标 这项研究包括鉴定区分SARS-CoV-2感染和疫苗接种的血清学反应， 开发和鉴定一套免疫测定和参考试剂， 询问对感染的免疫反应，以测量SARS-CoV-2适应性反应的关键 人群和风险群体，并描述康复期个人感染的特点。 这项初步研究将告诉我们很多关于感染者的适应性免疫反应的信息 并从SARS-CoV-2中恢复过来，并将阐明免疫系统在成功治疗SARS-CoV-2中的作用。 清除感染。它将提高我们对反应的动态和持续时间的理解， 表位特异性和其他定义签名，并将告知合理的设计和测试预防性 以及治疗性疫苗和单克隆抗体。此外，该议定书将为以下方面奠定基础： 对这种感染进行前瞻性研究，更好地界定关键的风险群体和知识差距。最后，本研究将 为目前进入临床试验管道的大量COVID-19疫苗做好网络准备。 首次试验的实验室、统计学和操作经验将是非常宝贵的准备和启动， 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

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.