tetano
Editor, Senior Moderator
iScience
. 2021 Dec 8;103602.
doi: 10.1016/j.isci.2021.103602. Online ahead of print.
Standardized two-step testing of antibody activity in COVID-19 convalescent plasma
Pavlo Gilchuk[SUP] 1 [/SUP], Isaac Thomsen[SUP] 2 3 [/SUP], Sandra Yoder[SUP] 2 3 [/SUP], Eric Brady[SUP] 2 3 [/SUP], James D Chappell[SUP] 2 [/SUP], Laura J Stevens[SUP] 2 [/SUP], Mark R Denison[SUP] 2 4 [/SUP], Rachel E Sutton[SUP] 1 [/SUP], Rita E Chen[SUP] 5 4 [/SUP], Laura A VanBlargan[SUP] 5 [/SUP], Naveen Suryadevara[SUP] 1 [/SUP], Seth J Zost[SUP] 1 [/SUP], Jonathan Schmitz[SUP] 6 7 [/SUP], Jill M Pulley[SUP] 8 [/SUP], Michael S Diamond[SUP] 5 4 9 10 [/SUP], Jillian P Rhoads[SUP] 8 [/SUP], Gordon R Bernard[SUP] 8 11 [/SUP], Wesley H Self[SUP] 8 12 [/SUP], Todd W Rice[SUP] 8 11 [/SUP], Allison P Wheeler[SUP] 2 6 [/SUP], James E Crowe Jr[SUP] 1 2 6 [/SUP], Robert H Carnahan[SUP] 1 2 [/SUP]
Affiliations
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.
Keywords: COVID-19; SARS-CoV-2; antibodies; antibodies, neutralizing; antibodies, viral; convalescent plasma; coronavirus.
. 2021 Dec 8;103602.
doi: 10.1016/j.isci.2021.103602. Online ahead of print.
Standardized two-step testing of antibody activity in COVID-19 convalescent plasma
Pavlo Gilchuk[SUP] 1 [/SUP], Isaac Thomsen[SUP] 2 3 [/SUP], Sandra Yoder[SUP] 2 3 [/SUP], Eric Brady[SUP] 2 3 [/SUP], James D Chappell[SUP] 2 [/SUP], Laura J Stevens[SUP] 2 [/SUP], Mark R Denison[SUP] 2 4 [/SUP], Rachel E Sutton[SUP] 1 [/SUP], Rita E Chen[SUP] 5 4 [/SUP], Laura A VanBlargan[SUP] 5 [/SUP], Naveen Suryadevara[SUP] 1 [/SUP], Seth J Zost[SUP] 1 [/SUP], Jonathan Schmitz[SUP] 6 7 [/SUP], Jill M Pulley[SUP] 8 [/SUP], Michael S Diamond[SUP] 5 4 9 10 [/SUP], Jillian P Rhoads[SUP] 8 [/SUP], Gordon R Bernard[SUP] 8 11 [/SUP], Wesley H Self[SUP] 8 12 [/SUP], Todd W Rice[SUP] 8 11 [/SUP], Allison P Wheeler[SUP] 2 6 [/SUP], James E Crowe Jr[SUP] 1 2 6 [/SUP], Robert H Carnahan[SUP] 1 2 [/SUP]
Affiliations
- 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.
Keywords: COVID-19; SARS-CoV-2; antibodies; antibodies, neutralizing; antibodies, viral; convalescent plasma; coronavirus.