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 language | English |
|---|---|
| Article number | 103602 |
| Journal | iScience |
| Volume | 25 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 21 2022 |
Keywords
- Immunology
- Virology
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In: iScience, Vol. 25, No. 1, 103602, 21.01.2022.
Research output: Contribution to journal › Article › peer-review
TY - JOUR
T1 - Standardized two-step testing of antibody activity in COVID-19 convalescent plasma
AU - Gilchuk, Pavlo
AU - Thomsen, Isaac
AU - Yoder, Sandra
AU - Brady, Eric
AU - Chappell, James D.
AU - Stevens, Laura J.
AU - Denison, Mark R.
AU - Sutton, Rachel E.
AU - Chen, Rita E.
AU - VanBlargan, Laura A.
AU - Suryadevara, Naveenchandra
AU - Zost, Seth J.
AU - Schmitz, Jonathan
AU - Pulley, Jill M.
AU - Diamond, Michael S.
AU - Rhoads, Jillian P.
AU - Bernard, Gordon R.
AU - Self, Wesley H.
AU - Rice, Todd W.
AU - Wheeler, Allison P.
AU - Crowe, James E.
AU - Carnahan, Robert H.
N1 - Funding Information: I.T. reports grants from NIH/NIAID, during the conduct of the study, and has served as a consultant for Nashville Biosciences and Horizon Therapeutics. J. D. C., L.J.S., and M.R.D. report grants from NIH/NCATS, during the conduct of the study. T.W.R. reports grants from NIH/NCATS, during the conduct of the study; personal fees from Cumberland Pharmaceuticals, Inc, personal fees from Sanofi Pharma, and personal fees from Cytovale, outside the submitted work. T.G.S. reports grants from NIH, during the conduct of the study. W.H.S. reports grants from NCATS of the NIH, during the conduct of the study. M.S.D. is a consultant for Inbios, Vir Biotechnology, Fortress Biotech, and Carnival Corporation and on the Scientific Advisory Boards of Moderna and Immunome. The Diamond laboratory has received funding support in sponsored research agreements from Moderna, Vir Biotechnology, and Emergent BioSolutions. J.E.C. has served as a consultant for Luna Biologics, is a member of the Scientific Advisory Board of Meissa Vaccines and is Founder of IDBiologics. The Crowe laboratory at Vanderbilt University Medical Center has received sponsored research agreements from Takeda Vaccines, IDBiologics, and AstraZeneca and grants from NIH, and DARPA during the conduct of the study. Vanderbilt University has applied for patents related to antibodies described in this paper. All other authors declare no competing interests. Funding Information: We thank Agilent Technologies for their assistance with RTCA methods development and technical support, Leinco Technologies for performing Leinco Trace IgG Micro-ELISA and ImmunoRank Neutralization assays, Xiaotao Lu (VUMC) and Tia Hughes (VUMC) for technical support of SARS-CoV-2 neutralization testing, and Thomas Stewart, Wang Li, and Chris Lindsell for their advice for statistical analysis. VSV-SARS-CoV-2 was a kind gift from Sean Whelan (Washington University School of Medicine). This work was supported by the National Institute of Health (NIH) National Center for Advancing Translational Sciences (NCATS) grant 3UL1TR002243-04S4 , Vanderbilt Institute for Infection, Immunology, and Inflammation (VI4), the Hays Foundation COVID-19 Research Fund (to I.T.), Defense Advanced Research Projects Agency (DARPA) grant HR0011-18-2-0001 , U.S. N.I.H. contract 75N93019C00074, the Dolly Parton COVID-19 Research Fund at Vanderbilt, and a grant from Fast Grants, Mercatus Center, George Mason University. Reagents for the AdviseDx II IgG assay were provided under research agreement between Abbott Laboratories and VUMC. J.E.C. is a recipient of the 2019 Future Insight Prize from Merck KGaA, which supported this work with a grant. The content is solely the responsibility of the authors and does not represent the official views of the U.S. government or other sponsors. We thank the anonymous donors of the plasma samples for their consent, which has allowed WHO International standard for anti-SARS-CoV-2 human immunoglobulin to be prepared. We express our gratitude to those who have coordinated the collection of the convalescent plasma: Malcom Semple (University of Liverpool, UK), Lance Turtle (University of Liverpool, UK), Peter Openshaw (Imperial College London, UK), and Kenneth Baillie (University of Edinburgh) on behalf of the ISARIC4C Investigators; Heli Harvala Simmonds and David Roberts (National Health Service Blood and Transplant, UK). We also thank NIBSC Standards Production and Development staff for the formulation and distribution of materials. Funding Information: We thank Agilent Technologies for their assistance with RTCA methods development and technical support, Leinco Technologies for performing Leinco Trace IgG Micro-ELISA and ImmunoRank Neutralization assays, Xiaotao Lu (VUMC) and Tia Hughes (VUMC) for technical support of SARS-CoV-2 neutralization testing, and Thomas Stewart, Wang Li, and Chris Lindsell for their advice for statistical analysis. VSV-SARS-CoV-2 was a kind gift from Sean Whelan (Washington University School of Medicine). This work was supported by the National Institute of Health (NIH) National Center for Advancing Translational Sciences (NCATS) grant 3UL1TR002243-04S4, Vanderbilt Institute for Infection, Immunology, and Inflammation (VI4), the Hays Foundation COVID-19 Research Fund (to I.T.), Defense Advanced Research Projects Agency (DARPA) grant HR0011-18-2-0001, U.S. N.I.H. contract 75N93019C00074, the Dolly Parton COVID-19 Research Fund at Vanderbilt, and a grant from Fast Grants, Mercatus Center, George Mason University. Reagents for the AdviseDx II IgG assay were provided under research agreement between Abbott Laboratories and VUMC. J.E.C. is a recipient of the 2019 Future Insight Prize from Merck KGaA, which supported this work with a grant. The content is solely the responsibility of the authors and does not represent the official views of the U.S. government or other sponsors. We thank the anonymous donors of the plasma samples for their consent, which has allowed WHO International standard for anti-SARS-CoV-2 human immunoglobulin to be prepared. We express our gratitude to those who have coordinated the collection of the convalescent plasma: Malcom Semple (University of Liverpool, UK), Lance Turtle (University of Liverpool, UK), Peter Openshaw (Imperial College London, UK), and Kenneth Baillie (University of Edinburgh) on behalf of the ISARIC4C Investigators; Heli Harvala Simmonds and David Roberts (National Health Service Blood and Transplant, UK). We also thank NIBSC Standards Production and Development staff for the formulation and distribution of materials. P.G. I.T. J.D.C. M.R.D. J.S. J.M.P. M.S.D. G.R.B. A.P.W. J.E.C. and R.H.C. planned the studies. J.P.R. and A.P.W. recruited the participants and coordinated plasma and serum samples collection. P.G. S.Y. E.B. L.J.S. R.E.S. R.E.C. L.A.V. and N.S. conducted experiments. P.G. I.T. S.Y. J.D.C. L.J.S. R.E.C. and S.Z. analyzed data, P.G. I.T. J.D.C. J.S. J.M.P. M.S.D. G.R.B. W.H.S. and T.W.R interpreted the studies. P.G. I.T. J.E.C. and R.H.C wrote the first draft of the paper. I.T. M.S.D. G.R.B. and J.E.C. obtained funding. All authors reviewed, edited, and approved the paper. I.T. reports grants from NIH/NIAID, during the conduct of the study, and has served as a consultant for Nashville Biosciences and Horizon Therapeutics. J. D. C. L.J.S. and M.R.D. report grants from NIH/NCATS, during the conduct of the study. T.W.R. reports grants from NIH/NCATS, during the conduct of the study; personal fees from Cumberland Pharmaceuticals, Inc, personal fees from Sanofi Pharma, and personal fees from Cytovale, outside the submitted work. T.G.S. reports grants from NIH, during the conduct of the study. W.H.S. reports grants from NCATS of the NIH, during the conduct of the study. M.S.D. is a consultant for Inbios, Vir Biotechnology, Fortress Biotech, and Carnival Corporation and on the Scientific Advisory Boards of Moderna and Immunome. The Diamond laboratory has received funding support in sponsored research agreements from Moderna, Vir Biotechnology, and Emergent BioSolutions. J.E.C. has served as a consultant for Luna Biologics, is a member of the Scientific Advisory Board of Meissa Vaccines and is Founder of IDBiologics. The Crowe laboratory at Vanderbilt University Medical Center has received sponsored research agreements from Takeda Vaccines, IDBiologics, and AstraZeneca and grants from NIH, and DARPA during the conduct of the study. Vanderbilt University has applied for patents related to antibodies described in this paper. All other authors declare no competing interests. Publisher Copyright: © 2021 The Authors
PY - 2022/1/21
Y1 - 2022/1/21
N2 - 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.
AB - 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.
KW - Immunology
KW - Virology
UR - http://www.scopus.com/inward/record.url?scp=85121625428&partnerID=8YFLogxK
U2 - 10.1016/j.isci.2021.103602
DO - 10.1016/j.isci.2021.103602
M3 - Article
C2 - 34901783
AN - SCOPUS:85121625428
SN - 2589-0042
VL - 25
JO - iScience
JF - iScience
IS - 1
M1 - 103602
ER -