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Master of Public Health

Standardized two-step testing of antibody activity in COVID-19 convalescent plasma

AUTHORS

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 , . iScience. 2021 12 8; 25(1). 103602

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.

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