Project Summary As the COVID-19 pandemic continues to spread across the United States it is imperative that we implement technologies to screen large swaths of the population for the presence of antibodies to SARS-CoV-2. Serological surveillance not only affords a measure of virus exposure within a community at large but also provides information necessary to predict outbreak dynamics. Furthermore, as our understanding of how humoral factors contribute to controlling (and possibly exacerbating) COVID-19, it will be essential to have methods in place to measure the “quantity” and “quality” of antibodies associated with both natural SARS-CoV- 2 exposure and candidate SARS-CoV-2 vaccines. This U01 proposal seeks to advance the use of dried blood spots (DBS) in conjunction with a Luminex-based microsphere immunoassay (MIA) to enable high-throughput (HT) population-wide serological surveillance for SARS-CoV-2. Specifically, the proposal will expand the HT- DBS assay to capture the breadth and complexity of SARS-CoV-2 antibody responses following natural infection, and develop a high-throughput competitive immunoassay (CIA) as a surrogate measure of SARS- CoV-2 neutralizing antibody titers in DBS. The proposed platform technologies to be developed at the Wadsworth Center will contribute directly to NCI’s mission to “… develop, validate, improve and implement serological testing and associated technologies…” to address the COVID-19 pandemic.