iScience (Jan 2022)

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. Wheeler,
  • James E. Crowe, Jr.,
  • Robert H. Carnahan

Journal volume & issue
Vol. 25, no. 1
p. 103602

Abstract

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Summary: 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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