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+...
Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Elsevier
2021-07-01
|
Series: | Cell Reports |
Subjects: | |
Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124721007294 |
_version_ | 1818886235815411712 |
---|---|
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. |
first_indexed | 2024-12-19T16:18:07Z |
format | Article |
id | doaj.art-f492dbc1e9954938a7e8625d4e1dc65e |
institution | Directory Open Access Journal |
issn | 2211-1247 |
language | English |
last_indexed | 2024-12-19T16:18:07Z |
publishDate | 2021-07-01 |
publisher | Elsevier |
record_format | Article |
series | Cell Reports |
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 |
work_keys_str_mv | AT madeleinefjennewein isolationandcharacterizationofcrossneutralizingcoronavirusantibodiesfromcovid19subjects AT annajmaccamy isolationandcharacterizationofcrossneutralizingcoronavirusantibodiesfromcovid19subjects AT nicholasrakins isolationandcharacterizationofcrossneutralizingcoronavirusantibodiesfromcovid19subjects AT junlifeng isolationandcharacterizationofcrossneutralizingcoronavirusantibodiesfromcovid19subjects AT leahjhomad isolationandcharacterizationofcrossneutralizingcoronavirusantibodiesfromcovid19subjects AT nicholaskhurlburt isolationandcharacterizationofcrossneutralizingcoronavirusantibodiesfromcovid19subjects AT emilieseydoux isolationandcharacterizationofcrossneutralizingcoronavirusantibodiesfromcovid19subjects AT yuhsinwan isolationandcharacterizationofcrossneutralizingcoronavirusantibodiesfromcovid19subjects AT andrewbstuart isolationandcharacterizationofcrossneutralizingcoronavirusantibodiesfromcovid19subjects AT venkataviswanadhedara isolationandcharacterizationofcrossneutralizingcoronavirusantibodiesfromcovid19subjects AT katharinefloyd isolationandcharacterizationofcrossneutralizingcoronavirusantibodiesfromcovid19subjects AT abigailvanderheiden isolationandcharacterizationofcrossneutralizingcoronavirusantibodiesfromcovid19subjects AT johnrmascola isolationandcharacterizationofcrossneutralizingcoronavirusantibodiesfromcovid19subjects AT nicoledoriarose isolationandcharacterizationofcrossneutralizingcoronavirusantibodiesfromcovid19subjects AT lingshuwang isolationandcharacterizationofcrossneutralizingcoronavirusantibodiesfromcovid19subjects AT eunsungyang isolationandcharacterizationofcrossneutralizingcoronavirusantibodiesfromcovid19subjects AT helenychu isolationandcharacterizationofcrossneutralizingcoronavirusantibodiesfromcovid19subjects AT jonathanltorres isolationandcharacterizationofcrossneutralizingcoronavirusantibodiesfromcovid19subjects AT gabrielozorowski isolationandcharacterizationofcrossneutralizingcoronavirusantibodiesfromcovid19subjects AT andrewbward isolationandcharacterizationofcrossneutralizingcoronavirusantibodiesfromcovid19subjects AT rachaelewhaley isolationandcharacterizationofcrossneutralizingcoronavirusantibodiesfromcovid19subjects AT kristenwcohen isolationandcharacterizationofcrossneutralizingcoronavirusantibodiesfromcovid19subjects AT mariepancera isolationandcharacterizationofcrossneutralizingcoronavirusantibodiesfromcovid19subjects AT mjulianamcelrath isolationandcharacterizationofcrossneutralizingcoronavirusantibodiesfromcovid19subjects AT janetaenglund isolationandcharacterizationofcrossneutralizingcoronavirusantibodiesfromcovid19subjects AT andresfinzi isolationandcharacterizationofcrossneutralizingcoronavirusantibodiesfromcovid19subjects AT mehulssuthar isolationandcharacterizationofcrossneutralizingcoronavirusantibodiesfromcovid19subjects AT andrewtmcguire isolationandcharacterizationofcrossneutralizingcoronavirusantibodiesfromcovid19subjects AT leonidasstamatatos isolationandcharacterizationofcrossneutralizingcoronavirusantibodiesfromcovid19subjects |