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Gilchuk P, Thomsen I, Yoder S, Brady E, Chappell JD, Stevens LJ, Denison MR, Sutton RE, Chen RE, VanBlargan LA, Suryadevara N, Zost SJ, Schmitz J, Pulley JM, Diamond MS, Rhoads JP, Bernard GR, Self WH, Rice TW, Wheeler AP, Crowe JE, Carnahan RH. Standardized two-step testing of antibody activity in COVID-19 convalescent plasma. IScience. 2022 Jan 21;25(25). 103602 p.
Abstract
The COVID-19 pandemic revealed an urgent need for rapid profiling of neutralizing antibody responses and development of antibody therapeutics. The current Food and Drug Administration-approved serological tests do not measure antibody-mediated viral neutralization, and there is a need for standardized quantitative neutralization assays. We report a high-throughput two-step profiling approach for identifying neutralizing convalescent plasma. Screening and downselection for serum antibody binding to the receptor-binding domain are followed by quantitative neutralization testing using a chimeric vesicular stomatitis virus expressing spike protein of SARS-CoV-2 in a real-time cell analysis assay. This approach enables a predictive screening process for identifying plasma units that neutralize SARS-CoV-2. To calibrate antibody neutralizing activity in serum from convalescent plasma donors, we introduce a neutralizing antibody standard reagent composed of two human antibodies that neutralize SARS-CoV strains, including SARS-CoV-2 variants of concern. Our results provide a framework for establishing a standardized assessment of antibody-based interventions against COVID-19.