Project Abstract This proposal outlines the scientific agenda for the COVID-19 Prevention Network (CoVPN) Vaccines Statistical and Data Management Center (SDMC) for implementation of cross-protocol work in support of COVID-19 phase 3 efficacy trials. With the global COVID-19 pandemic, we recognize a significant need for vaccines that modify COVID-19 in SARS-CoV-2 infected individuals. Addressing this gap, the HVTN SDMC has joined 4 other National Institute of Health (NIH) clinical trial networks to form the CoVPN, an enhanced network dedicated to developing globally effective vaccines for SARS-CoV-2. The innovation of the CoVPN SDMC and advantages to this work include the collective experience of our group- leader in statistical methods in vaccine evaluation, especially immune correlates assessment, and the long-standing relationships we have with the clinical and lab groups in the CoVPN lead Adapting and leveraging statistical methods for evaluating vaccines against other pathogens to SARS-CoV-2. E.g. causal inference methods for evaluating multiple types of formally defined correlates of protection including correlates of vaccine efficacy, mediators of vaccine efficacy, and stochastic-intervention effects on vaccine efficacy.

Project Narrative The outbreak of SARS-CoV-2 across the globe presents an unprecedented health risk to the world’s population and requires intensive study of key gaps in our understanding of the immune response and what adaptations lead to protective immunity. In this study, the CoVPN will apply its laboratory, biostatistical and vaccine trial leadership expertise to assess this response using unprecedented cross-protocol analytical techniques, tools, and methods to evaluate vaccine efficacy, safety signals, and epidemiological modeling tools.