Isolation and characterization of cross-neutralizing coronavirus antibodies from COVID-19+ subjects

Summary: SARS-CoV-2 is one of three coronaviruses that have crossed the animal-to-human barrier and caused widespread disease in the past two decades. The development of a universal human coronavirus vaccine could prevent future pandemics. We characterize 198 antibodies isolated from four COVID-19+...

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Main Authors: Madeleine F. Jennewein, Anna J. MacCamy, Nicholas R. Akins, Junli Feng, Leah J. Homad, Nicholas K. Hurlburt, Emilie Seydoux, Yu-Hsin Wan, Andrew B. Stuart, Venkata Viswanadh Edara, Katharine Floyd, Abigail Vanderheiden, John R. Mascola, Nicole Doria-Rose, Lingshu Wang, Eun Sung Yang, Helen Y. Chu, Jonathan L. Torres, Gabriel Ozorowski, Andrew B. Ward, Rachael E. Whaley, Kristen W. Cohen, Marie Pancera, M. Juliana McElrath, Janet A. Englund, Andrés Finzi, Mehul S. Suthar, Andrew T. McGuire, Leonidas Stamatatos
Format: Article
Language:English
Published: Elsevier 2021-07-01
Series:Cell Reports
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2211124721007294
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author Madeleine F. Jennewein
Anna J. MacCamy
Nicholas R. Akins
Junli Feng
Leah J. Homad
Nicholas K. Hurlburt
Emilie Seydoux
Yu-Hsin Wan
Andrew B. Stuart
Venkata Viswanadh Edara
Katharine Floyd
Abigail Vanderheiden
John R. Mascola
Nicole Doria-Rose
Lingshu Wang
Eun Sung Yang
Helen Y. Chu
Jonathan L. Torres
Gabriel Ozorowski
Andrew B. Ward
Rachael E. Whaley
Kristen W. Cohen
Marie Pancera
M. Juliana McElrath
Janet A. Englund
Andrés Finzi
Mehul S. Suthar
Andrew T. McGuire
Leonidas Stamatatos
author_facet Madeleine F. Jennewein
Anna J. MacCamy
Nicholas R. Akins
Junli Feng
Leah J. Homad
Nicholas K. Hurlburt
Emilie Seydoux
Yu-Hsin Wan
Andrew B. Stuart
Venkata Viswanadh Edara
Katharine Floyd
Abigail Vanderheiden
John R. Mascola
Nicole Doria-Rose
Lingshu Wang
Eun Sung Yang
Helen Y. Chu
Jonathan L. Torres
Gabriel Ozorowski
Andrew B. Ward
Rachael E. Whaley
Kristen W. Cohen
Marie Pancera
M. Juliana McElrath
Janet A. Englund
Andrés Finzi
Mehul S. Suthar
Andrew T. McGuire
Leonidas Stamatatos
author_sort Madeleine F. Jennewein
collection DOAJ
description Summary: SARS-CoV-2 is one of three coronaviruses that have crossed the animal-to-human barrier and caused widespread disease in the past two decades. The development of a universal human coronavirus vaccine could prevent future pandemics. We characterize 198 antibodies isolated from four COVID-19+ subjects and identify 14 SARS-CoV-2 neutralizing antibodies. One targets the N-terminal domain (NTD), one recognizes an epitope in S2, and 11 bind the receptor-binding domain (RBD). Three anti-RBD neutralizing antibodies cross-neutralize SARS-CoV-1 by effectively blocking binding of both the SARS-CoV-1 and SARS-CoV-2 RBDs to the ACE2 receptor. Using the K18-hACE transgenic mouse model, we demonstrate that the neutralization potency and antibody epitope specificity regulates the in vivo protective potential of anti-SARS-CoV-2 antibodies. All four cross-neutralizing antibodies neutralize the B.1.351 mutant strain. Thus, our study reveals that epitopes in S2 can serve as blueprints for the design of immunogens capable of eliciting cross-neutralizing coronavirus antibodies.
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spelling doaj.art-f492dbc1e9954938a7e8625d4e1dc65e2022-12-21T20:14:34ZengElsevierCell Reports2211-12472021-07-01362109353Isolation and characterization of cross-neutralizing coronavirus antibodies from COVID-19+ subjectsMadeleine F. Jennewein0Anna J. MacCamy1Nicholas R. Akins2Junli Feng3Leah J. Homad4Nicholas K. Hurlburt5Emilie Seydoux6Yu-Hsin Wan7Andrew B. Stuart8Venkata Viswanadh Edara9Katharine Floyd10Abigail Vanderheiden11John R. Mascola12Nicole Doria-Rose13Lingshu Wang14Eun Sung Yang15Helen Y. Chu16Jonathan L. Torres17Gabriel Ozorowski18Andrew B. Ward19Rachael E. Whaley20Kristen W. Cohen21Marie Pancera22M. Juliana McElrath23Janet A. Englund24Andrés Finzi25Mehul S. Suthar26Andrew T. McGuire27Leonidas Stamatatos28Fred Hutchinson Cancer Research Center, Vaccines and Infectious Disease Division, Seattle, WA 98109, USAFred Hutchinson Cancer Research Center, Vaccines and Infectious Disease Division, Seattle, WA 98109, USAFred Hutchinson Cancer Research Center, Vaccines and Infectious Disease Division, Seattle, WA 98109, USAFred Hutchinson Cancer Research Center, Vaccines and Infectious Disease Division, Seattle, WA 98109, USAFred Hutchinson Cancer Research Center, Vaccines and Infectious Disease Division, Seattle, WA 98109, USAFred Hutchinson Cancer Research Center, Vaccines and Infectious Disease Division, Seattle, WA 98109, USAFred Hutchinson Cancer Research Center, Vaccines and Infectious Disease Division, Seattle, WA 98109, USAFred Hutchinson Cancer Research Center, Vaccines and Infectious Disease Division, Seattle, WA 98109, USAFred Hutchinson Cancer Research Center, Vaccines and Infectious Disease Division, Seattle, WA 98109, USACenter for Childhood Infections and Vaccines of Children’s Healthcare of Atlanta, Department of Pediatrics, Emory University School of Medicine, Emory Vaccine Center, Yerkes National Primate Research Center, Atlanta, GA 30322, USACenter for Childhood Infections and Vaccines of Children’s Healthcare of Atlanta, Department of Pediatrics, Emory University School of Medicine, Emory Vaccine Center, Yerkes National Primate Research Center, Atlanta, GA 30322, USACenter for Childhood Infections and Vaccines of Children’s Healthcare of Atlanta, Department of Pediatrics, Emory University School of Medicine, Emory Vaccine Center, Yerkes National Primate Research Center, Atlanta, GA 30322, USAVaccine Research Center, NIAID, NIH, Bethesda, MD 20892, USAVaccine Research Center, NIAID, NIH, Bethesda, MD 20892, USAVaccine Research Center, NIAID, NIH, Bethesda, MD 20892, USAVaccine Research Center, NIAID, NIH, Bethesda, MD 20892, USAUniversity of Washington, Department of Medicine, Seattle, WA 98109, USADepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USADepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USADepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USAFred Hutchinson Cancer Research Center, Vaccines and Infectious Disease Division, Seattle, WA 98109, USAFred Hutchinson Cancer Research Center, Vaccines and Infectious Disease Division, Seattle, WA 98109, USAFred Hutchinson Cancer Research Center, Vaccines and Infectious Disease Division, Seattle, WA 98109, USA; Vaccine Research Center, NIAID, NIH, Bethesda, MD 20892, USAFred Hutchinson Cancer Research Center, Vaccines and Infectious Disease Division, Seattle, WA 98109, USA; University of Washington, Department of Medicine, Seattle, WA 98109, USA; University of Washington, Department of Global Health, Seattle, WA 98109, USADepartment of Pediatrics, University of Washington and Seattle Children’s Research Institute, Seattle, WA 98109, USAUniversité de Montréal, Montreal, QC, CanadaCenter for Childhood Infections and Vaccines of Children’s Healthcare of Atlanta, Department of Pediatrics, Emory University School of Medicine, Emory Vaccine Center, Yerkes National Primate Research Center, Atlanta, GA 30322, USA; Corresponding authorFred Hutchinson Cancer Research Center, Vaccines and Infectious Disease Division, Seattle, WA 98109, USA; University of Washington, Department of Global Health, Seattle, WA 98109, USA; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA 98195, USA; Corresponding authorFred Hutchinson Cancer Research Center, Vaccines and Infectious Disease Division, Seattle, WA 98109, USA; University of Washington, Department of Global Health, Seattle, WA 98109, USA; Corresponding authorSummary: SARS-CoV-2 is one of three coronaviruses that have crossed the animal-to-human barrier and caused widespread disease in the past two decades. The development of a universal human coronavirus vaccine could prevent future pandemics. We characterize 198 antibodies isolated from four COVID-19+ subjects and identify 14 SARS-CoV-2 neutralizing antibodies. One targets the N-terminal domain (NTD), one recognizes an epitope in S2, and 11 bind the receptor-binding domain (RBD). Three anti-RBD neutralizing antibodies cross-neutralize SARS-CoV-1 by effectively blocking binding of both the SARS-CoV-1 and SARS-CoV-2 RBDs to the ACE2 receptor. Using the K18-hACE transgenic mouse model, we demonstrate that the neutralization potency and antibody epitope specificity regulates the in vivo protective potential of anti-SARS-CoV-2 antibodies. All four cross-neutralizing antibodies neutralize the B.1.351 mutant strain. Thus, our study reveals that epitopes in S2 can serve as blueprints for the design of immunogens capable of eliciting cross-neutralizing coronavirus antibodies.http://www.sciencedirect.com/science/article/pii/S2211124721007294SARS-CoV-2SARS-CoV-1S2 subunitRBDNTDneutralization
spellingShingle Madeleine F. Jennewein
Anna J. MacCamy
Nicholas R. Akins
Junli Feng
Leah J. Homad
Nicholas K. Hurlburt
Emilie Seydoux
Yu-Hsin Wan
Andrew B. Stuart
Venkata Viswanadh Edara
Katharine Floyd
Abigail Vanderheiden
John R. Mascola
Nicole Doria-Rose
Lingshu Wang
Eun Sung Yang
Helen Y. Chu
Jonathan L. Torres
Gabriel Ozorowski
Andrew B. Ward
Rachael E. Whaley
Kristen W. Cohen
Marie Pancera
M. Juliana McElrath
Janet A. Englund
Andrés Finzi
Mehul S. Suthar
Andrew T. McGuire
Leonidas Stamatatos
Isolation and characterization of cross-neutralizing coronavirus antibodies from COVID-19+ subjects
Cell Reports
SARS-CoV-2
SARS-CoV-1
S2 subunit
RBD
NTD
neutralization
title Isolation and characterization of cross-neutralizing coronavirus antibodies from COVID-19+ subjects
title_full Isolation and characterization of cross-neutralizing coronavirus antibodies from COVID-19+ subjects
title_fullStr Isolation and characterization of cross-neutralizing coronavirus antibodies from COVID-19+ subjects
title_full_unstemmed Isolation and characterization of cross-neutralizing coronavirus antibodies from COVID-19+ subjects
title_short Isolation and characterization of cross-neutralizing coronavirus antibodies from COVID-19+ subjects
title_sort isolation and characterization of cross neutralizing coronavirus antibodies from covid 19 subjects
topic SARS-CoV-2
SARS-CoV-1
S2 subunit
RBD
NTD
neutralization
url http://www.sciencedirect.com/science/article/pii/S2211124721007294
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