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

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.