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

Pavlo Gilchuk, Isaac Thomsen, Sandra Yoder, Eric Brady, James D. Chappell, Laura J. Stevens, Mark R. Denison, Rachel E. Sutton, Rita E. Chen, Laura A. VanBlargan, Naveenchandra Suryadevara, Seth J. Zost, Jonathan Schmitz, Jill M. Pulley, Michael S. Diamond, Jillian P. Rhoads, Gordon R. Bernard, Wesley H. Self, Todd W. Rice, Allison P. WheelerJames E. Crowe, Robert H. Carnahan

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

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.

Original languageEnglish
Article number103602
JournaliScience
Volume25
Issue number1
DOIs
StatePublished - Jan 21 2022

Keywords

  • Immunology
  • Virology

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