CoVPN 3006: A randomized controlled study to assess SARS-CoV-2 infection, viral shedding, and subsequent potential transmission in university students immunized with Moderna COVID-19 Vaccine

项目摘要 该提案概述了COVID-19预防网络（CoVPN）疫苗的科学议程 领导运营中心（COVID-19）负责实施名为“随机 对照研究，以评估SARS-CoV-2感染，病毒脱落和随后的潜在传播， 大学生接种了Moderna COVID-19疫苗。” 随着全球COVID-19大流行，我们认识到对SARS-CoV-2疫苗的巨大需求， 减少暴露个体的病毒感染，减少感染个体的病毒脱落量， 从受感染者传播到密切接触者。为应对2019冠状病毒病疫情，国家 美国卫生研究院（NIH）领导了CoVPN的快速构建，与5个NIH支持的临床试验网络合作， 在145个美国（US）和71个国际临床试验中建立一个增强的医生-科学家网络 在17个国家建立了专门用于开发全球有效的SARS-CoV-2疫苗的研究中心。由于其广泛的 HIV疫苗试验网络（HVTN）在过去20年中实施全球HIV疫苗试验的经验 该公司被选为CoVPN疫苗试验的实验室。 本研究将监测联邦药品监督管理局（FDA）紧急使用授权（EUA） Moderna COVID-19疫苗用于预防立即接种与延迟接种大学生的感染 队列。参与者将从美国20多所大学招募，其中包括三所 队列：12，000名年龄在18 - 26岁之间的健康志愿者，接受立即（第0个月）或延迟（第10个月）治疗。 4)疫苗接种（主要队列），多达24，000名志愿者接受大学SARS-CoV-2检测，他们与 与主要队列受试者（前瞻性密切接触（PCC）队列）的身体接近度，以及 每例病例3名接触者，共计1，500名与SARS密切接触者- 来自主要队列（病例确诊密切接触者（CACC）队列）的CoV-2阳性病例。 主研究的受试者将对随机化揭盲，并将在第1天（D1）接种疫苗 立即接种组在D113和D29，延迟接种组在D113和D141。他们将 每天自我采集鼻拭子，以捕获4个月内发生的所有SARS-CoVE-2感染事件， 随访并记录病毒脱落的整个过程-从感染开始到病毒清除- 无症状感染者和有症状感染者。最大限度地减少受试者负担， 效率许多研究程序将远程发生。SARS-CoV-2感染者将每天完成电子邮件， 记录症状的日记。所有试验终点测定将使用合格和经验证的测定进行， 将在基线血清阴性的受试者中进行诊断和免疫监测以及主要分析 参与者（目标是血清阳性率< 10%）。 本研究的具体目的是评估Moderna COVID-19疫苗预防SARS的临床疗效- 初治成人中的CoV-2感染;评价疫苗对鼻病毒载量峰值的影响，作为感染指标 和传染性的代理;评估疫苗对SARS-CoV-2继发性传播的影响 感染;评估疫苗对COVID-19疾病的有效性;并评估疫苗的免疫原性。 疫苗这项试验将大大增加我们对这些疫苗在减少 和改变感染以及防止传播给居住在接种个体附近的人。它将 也提高了我们对SARS-CoV-2 mRNA接种个体中病毒动力学的理解。最后 这项试验的结果将用于修改未来的COVID-19疫苗试验，这些试验既针对个人保护， 防止传播。

Project Abstract This proposal outlines the scientific agenda for the COVID-19 Prevention Network (CoVPN) Vaccines Leadership Operations Center (LOC) for implementation of the COVID-19 vaccine trial entitled “A randomized controlled study to assess SARS-CoV-2 infection, viral shedding, and subsequent potential transmission in university students immunized with Moderna COVID-19 Vaccine.” With the global COVID-19 pandemic, we recognize a significant need for SARS-CoV-2 vaccines that reduce infection in exposed individuals, reduce the amount of viral shedding in infected individuals and reduce transmission from infected individuals to close contacts. Addressing the COVID-19 pandemic, the National Institutes of Health (NIH) led rapid constitution of the CoVPN, partnering 5 NIH supported clinical trial networks, to create an enhanced network of physician-scientists at 145 United States (US) and 71 international clinical trial sites in 17 countries dedicated to developing globally effective vaccines for SARS-CoV-2. Due to its extensive experience implementing global HIV vaccine trials over the last 20 years, the HIV Vaccine Trials Network (HVTN) LOC was selected as the LOC for CoVPN vaccine trials. This study will monitor the efficacy of the Federal Drug Administration (FDA) Emergency Use Authorized (EUA) Moderna COVID-19 Vaccine to prevent infection in an immediate versus delayed vaccination college student cohort. Participants will be recruited from over 20 universities across the United States and will include three cohorts: 12,000 healthy volunteers aged 18 through 26 years to receive immediate (month 0) or delayed (month 4) vaccination (Main Cohort), up to 24,000 volunteers subject to university SARS-CoV-2 testing who are in close physical proximity with main cohort participants (Prospective Close Contact (PCC) Cohort), and approximately 3 contacts per incidence case for a total of up to 1,500 individuals who have been in close contact with a SARS- CoV-2 positive case from the Main Cohort (Case-Ascertained Close Contact (CACC) Cohort). Participants in the main study will be unblinded to randomization and will be administered vaccine at day 1 (D1) and D29 for the immediate vaccination arm, and at D113 and D141 for the delayed vaccination arm. They will self-collect nasal swabs daily in order to capture all incident SARS-CoVE-2 infection events over 4 months of follow-up and to capture the full course of viral shedding – from onset of infection to viral clearance – among those with both asymptomatic and symptomatic infection. To minimize participant burden and maximize study efficiency many study procedures will occur remotely. SARS-CoV-2 infected participants will complete daily e- diaries to capture symptoms. All trial endpoint assays will be done using qualified and validated assays for diagnosis and immune monitoring and the primary analyses will be conducted among baseline seronegative participants (targeting an entry seropositive rate of < 10%). Specific aims of this study are to assess the clinical efficacy of the Moderna COVID-19 Vaccine to prevent SARS- CoV-2 infection in naïve adults; to evaluate the vaccine effect on peak nasal viral load as a measure of infection and proxy of infectiousness; to evaluate the impact of the vaccine on secondary transmission of SARS-CoV-2 infection; to evaluate vaccine efficacy against COVID-19 disease; and to evaluate the immunogenicity of the vaccine. This trial will add a great deal to our understanding on how effective these vaccines are in reducing and modifying infection as well as preventing transmission to persons living near vaccinated individuals. It will also improve our understanding of the viral dynamics in SARS-CoV-2 mRNA vaccinated individuals. Lastly, the results of this trial will be used to modify future COVID-19 vaccine trials targeting both personal protection and prevention of transmission.