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 该提案概述了新冠肺炎预防网络疫苗的科学议程 领导运营中心(LOC)实施名为“A随机对照试验的新冠肺炎”疫苗试验 一项评估SARS-CoV-2感染、病毒脱落和随后潜在传播的对照研究 大学生接种了摩迪纳新冠肺炎疫苗。 随着全球新冠肺炎的流行，我们认识到对SARS-CoV-2疫苗的巨大需求，以减少 在暴露的个人中感染，减少受感染个人的病毒脱落量，并减少 从感染者向密切接触者传播。应对新冠肺炎大流行，国家 卫生研究院(NIH)领导了CoVPN的快速建立，与NIH支持的5个临床试验网络合作， 在145个美国(美国)和71个国际临床试验中创建增强的医生-科学家网络 17个国家的网站致力于开发全球有效的SARS-CoV-2疫苗。由于其广泛性 过去20年实施全球艾滋病毒疫苗试验的经验，艾滋病毒疫苗试验网络(HVTN) LoC被选为CoVPN疫苗试验的LOC。 这项研究将监测联邦药物管理局(FDA)紧急使用授权(EUA)的疗效。 现代新冠肺炎疫苗预防大学生立即接种与延迟接种感染的比较 一群人。参与者将从全美20多所大学招募，其中包括3所 队列：12,000名年龄在18岁到26岁之间的健康志愿者立即(0个月)或延迟(1个月)接受治疗 4)接种疫苗(主要队列)，多达24,000名接受大学SARS-CoV-2检测的志愿者接近 与主要队列参与者(预期密切接触(PCC)队列)的物理距离，以及大约 每宗个案有3名接触者，最多可达1,500名曾与SARS有密切接触的人士- 主要队列(病例确定密切接触(CACC)队列)的CoV-2阳性病例。 主要研究的参与者将不会对随机分组视而不见，并将在第一天(D1)接种疫苗。 立即接种臂为D29，延迟接种臂为D113和D141。他们会 每天自行收集鼻拭子，以捕捉过去4个月发生的所有SARS-Cove-2感染事件 跟踪并记录病毒从感染开始到病毒清除的全过程-- 既有无症状感染又有症状感染的患者。最大限度地减少参与者的负担，最大限度地提高学习效率 效率许多研究程序将远程进行。感染SARS-CoV-2的参与者将完成日常电子- 用日记来捕捉症状。所有试验终点分析都将使用合格和有效的分析 诊断、免疫监测和初步分析将在基线血清阴性者中进行 参与者(目标是入境血清阳性率为10%)。 这项研究的具体目的是评估现代新冠肺炎疫苗预防SARS的临床疗效。 幼稚成人的CoV-2感染；评估疫苗对鼻腔病毒载量峰值的影响作为感染的衡量标准 和传染性的替代；评价疫苗对SARS-CoV-2二次传播的影响 以评价新冠肺炎疫苗的效力，并评价该疫苗的免疫原性。 疫苗。这项试验将极大地加深我们对这些疫苗在减少 以及改善感染以及防止向居住在接种疫苗个人附近的人传播。会的 也提高了我们对SARS-CoV-2mRNA疫苗接种个体中病毒动力学的理解。最后， 这项试验的结果将被用于修改未来针对个人保护和 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.