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iScience. 2021 Dec 08;103602. doi: 10.1016/j.isci.2021.103602. Epub 2021 Dec 08.

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

iScience

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, Naveen 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, Robert H Carnahan

Affiliations

  1. Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN, 37232, USA.
  2. Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, 37232, U.S.A.
  3. Vanderbilt Vaccine Research Program, Vanderbilt University Medical Center, Nashville, TN, USA.
  4. Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO, USA.
  5. Department of Medicine, Washington University School of Medicine, St. Louis, MO, U.S.A.
  6. Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, 37232, USA.
  7. Department of Urology, Vanderbilt University Medical Center, Nashville, TN, 37232, USA.
  8. Vanderbilt Institute for Clinical and Translational Research, Vanderbilt University Medical Center, Nashville, TN, USA.
  9. Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA.
  10. Andrew M. and Jane M. Bursky Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, Saint Louis, MO, USA.
  11. Department of Medicine, Division of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, TN, 37232, USA.
  12. Department of Emergency Medicine, Vanderbilt University Medical Center, Nashville, TN, 37232, USA.

PMID: 34901783 PMCID: PMC8653399 DOI: 10.1016/j.isci.2021.103602

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 down-selection 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.

© 2021.

Keywords: COVID-19; SARS-CoV-2; antibodies; antibodies, neutralizing; antibodies, viral; convalescent plasma; coronavirus

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