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. Due to the global COVID-19 pandemic, there is a significant need for a preventative SARS-CoV-2 vaccine. Addressing this gap, the HVTN 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 CoVPN Statistical Center works across studies in protocol development for all CoVPN COVID vaccine trials and bears responsibility for ensuring harmonization of data and methods across trials. Thus, we have great insight into the comparability between trials with respect to endpoints and their measurement, baseline characteristics, and study populations. Additionally, the CoVPN Statistical Center brings its unique resources in terms of the background and expertise of our group: we are leaders in statistical methods in vaccine evaluation, especially for immune correlates assessment. Our work is informed by our long-standing and deep collaborative relationships with the clinical and lab groups in the CoVPN. In this study, the CoVPN Statistical Center will apply its world class laboratory, biostatistical and vaccine trial leadership expertise to assess COVID-19 vaccine-induced responses using cutting-edge cross-protocol statistical methods for evaluating vaccine efficacy, vaccine safety signals, incidence of infection and disease, and immunological correlates of protection.