Nature, volume 584, issue 7821, pages 443-449

Potently neutralizing and protective human antibodies against SARS-CoV-2

Seth J. Zost ¹

Pavlo Gilchuk ¹

James B. Case ²

Elad Binshtein ¹

Rita E. Chen ^{2, 3}

Joseph P Nkolola ⁴

Alexandra Schäfer ⁵

Joseph X Reidy ¹

Andrew Trivette ¹

Rachel S. Nargi ¹

Rachel E. Sutton ¹

Naveenchandra Suryadevara ¹

David R. Martinez ⁵

Lauren E Williamson ⁶

Elaine C. Chen ⁶

Taylor Jones ¹

Samuel Day ¹

Luke Myers ¹

Ahmed O. Hassan ²

Natasha M. Kafai ^{2, 3}

Emma S Winkler ^{2, 3}

Julie M. Fox ²

Swathi Shrihari ²

Benjamin K Mueller ⁷

Jens Meiler ^{7, 8}

Abishek Chandrashekar ⁴

Noe B. Mercado ⁴

James J Steinhardt ⁹

Kuishu Ren ¹⁰

Yueh-Ming Loo ¹⁰

Nicole L. Kallewaard ¹⁰

Broc T Mccune ²

Shamus P. Keeler ^{2, 11}

Michael J. HOLTZMAN ^{2, 11}

Dan H. Barouch ⁴

Lisa E. Gralinski ⁵

Ralph S Baric ⁵

Larissa B Thackray ²

Michael S. Diamond ^{2, 3, 12, 13}

Robert H. Carnahan ^{1, 14}

James Crowe ^{1, 6, 14}

Hide authors affiliations Show authors affiliations: 14 affiliations

Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, USA |

Department of Medicine, Washington University School of Medicine, St Louis, USA |

Department of Pathology and Immunology, Washington University School Of Medicine, St Louis, USA |

⁴

Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, USA |

⁵

Department of Epidemiology, University of North Carolina At Chapel Hill, Chapel Hill, USA |

⁶

Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, USA |

⁷

Department of Chemistry, Vanderbilt University, Nashville, USA |

⁸

Leipzig University Medical School, Institute for Drug Discovery, Leipzig, Germany |

⁹

Antibody Discovery and Protein Engineering, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, USA |

¹⁰

Microbial Sciences, Biopharmaceuticals R&D, AstraZeneca, Gaithersburg, USA |

¹¹

Division of Pulmonary and Critical Care Medicine, Washington University School of Medicine, St Louis, USA |

¹²

Andrew M. and Jane M. Bursky Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, St Louis, USA |

¹³

Department of Molecular Microbiology, Washington University School of Medicine, St Louis, USA |

¹⁴

Department of Pediatrics, Vanderbilt University Medical Center, Nashville, USA |

Publication type: Journal Article

Publication date: 2020-07-15

Springer Nature

Journal: Nature

Quartile SCImago

Quartile WOS

Impact factor: 64.8

ISSN: 00280836, 14764687

DOI: 10.1038/s41586-020-2548-6

Copy DOI

PubMed ID: 32668443

Multidisciplinary

Abstract

The ongoing pandemic of coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a major threat to global health1 and the medical countermeasures available so far are limited2,3. Moreover, we currently lack a thorough understanding of the mechanisms of humoral immunity to SARS-CoV-24. Here we analyse a large panel of human monoclonal antibodies that target the spike (S) glycoprotein5, and identify several that exhibit potent neutralizing activity and fully block the receptor-binding domain of the S protein (SRBD) from interacting with human angiotensin-converting enzyme 2 (ACE2). Using competition-binding, structural and functional studies, we show that the monoclonal antibodies can be clustered into classes that recognize distinct epitopes on the SRBD, as well as distinct conformational states of the S trimer. Two potently neutralizing monoclonal antibodies, COV2-2196 and COV2-2130, which recognize non-overlapping sites, bound simultaneously to the S protein and neutralized wild-type SARS-CoV-2 virus in a synergistic manner. In two mouse models of SARS-CoV-2 infection, passive transfer of COV2-2196, COV2-2130 or a combination of both of these antibodies protected mice from weight loss and reduced the viral burden and levels of inflammation in the lungs. In addition, passive transfer of either of two of the most potent ACE2-blocking monoclonal antibodies (COV2-2196 or COV2-2381) as monotherapy protected rhesus macaques from SARS-CoV-2 infection. These results identify protective epitopes on the SRBD and provide a structure-based framework for rational vaccine design and the selection of robust immunotherapeutic agents. An analysis identifies human monoclonal antibodies that potently neutralize wild-type SARS-CoV-2 and protect animals from disease, including two that synergize in a cocktail, suggesting that these could be candidates for use as therapeutic agents for the treatment of COVID-19 in humans.

By date By citations

Top-30

Citations by journals

	5 10 15 20 25 30 35
Nature Communications	Nature Communications, 35, 3.67% Nature Communications 35 publications, 3.67%
Frontiers in Immunology	Frontiers in Immunology, 28, 2.94% Frontiers in Immunology 28 publications, 2.94%
Cell Reports	Cell Reports, 25, 2.62% Cell Reports 25 publications, 2.62%
Viruses	Viruses, 19, 1.99% Viruses 19 publications, 1.99%
Nature	Nature, 19, 1.99% Nature 19 publications, 1.99%
Cell	Cell, 19, 1.99% Cell 19 publications, 1.99%
Vaccines	Vaccines, 16, 1.68% Vaccines 16 publications, 1.68%
Science	Science, 13, 1.36% Science 13 publications, 1.36%
PLoS Pathogens	PLoS Pathogens, 13, 1.36% PLoS Pathogens 13 publications, 1.36%
Cell Host and Microbe	Cell Host and Microbe, 13, 1.36% Cell Host and Microbe 13 publications, 1.36%
Immunity	Immunity, 12, 1.26% Immunity 12 publications, 1.26%
Scientific Reports	Scientific Reports, 12, 1.26% Scientific Reports 12 publications, 1.26%
Proceedings of the National Academy of Sciences of the United States of America	Proceedings of the National Academy of Sciences of the United States of America, 11, 1.15% Proceedings of the National Academy of Sciences of the United States of America 11 publications, 1.15%
Science Translational Medicine	Science Translational Medicine, 10, 1.05% Science Translational Medicine 10 publications, 1.05%
Cell Reports Medicine	Cell Reports Medicine, 10, 1.05% Cell Reports Medicine 10 publications, 1.05%
Journal of Virology	Journal of Virology, 10, 1.05% Journal of Virology 10 publications, 1.05%
Emerging Microbes and Infections	Emerging Microbes and Infections, 9, 0.94% Emerging Microbes and Infections 9 publications, 0.94%
International Journal of Molecular Sciences	International Journal of Molecular Sciences, 8, 0.84% International Journal of Molecular Sciences 8 publications, 0.84%
iScience	iScience, 8, 0.84% iScience 8 publications, 0.84%
Science advances	Science advances, 8, 0.84% Science advances 8 publications, 0.84%
mAbs	mAbs, 7, 0.73% mAbs 7 publications, 0.73%
Cell Discovery	Cell Discovery, 6, 0.63% Cell Discovery 6 publications, 0.63%
Science immunology	Science immunology, 5, 0.52% Science immunology 5 publications, 0.52%
Journal of Clinical Investigation	Journal of Clinical Investigation, 5, 0.52% Journal of Clinical Investigation 5 publications, 0.52%
Pathogens	Pathogens, 5, 0.52% Pathogens 5 publications, 0.52%
Pharmaceutics	Pharmaceutics, 5, 0.52% Pharmaceutics 5 publications, 0.52%
BMC Infectious Diseases	BMC Infectious Diseases, 5, 0.52% BMC Infectious Diseases 5 publications, 0.52%
Nature Reviews Immunology	Nature Reviews Immunology, 5, 0.52% Nature Reviews Immunology 5 publications, 0.52%
Signal Transduction and Targeted Therapy	Signal Transduction and Targeted Therapy, 5, 0.52% Signal Transduction and Targeted Therapy 5 publications, 0.52%
	5 10 15 20 25 30 35

Citations by publishers

	50 100 150 200 250
Cold Spring Harbor Laboratory	Cold Spring Harbor Laboratory, 216, 22.67% Cold Spring Harbor Laboratory 216 publications, 22.67%
Elsevier	Elsevier, 185, 19.41% Elsevier 185 publications, 19.41%
Springer Nature	Springer Nature, 167, 17.52% Springer Nature 167 publications, 17.52%
Multidisciplinary Digital Publishing Institute (MDPI)	Multidisciplinary Digital Publishing Institute (MDPI), 70, 7.35% Multidisciplinary Digital Publishing Institute (MDPI) 70 publications, 7.35%
Wiley	Wiley, 44, 4.62% Wiley 44 publications, 4.62%
American Association for the Advancement of Science (AAAS)	American Association for the Advancement of Science (AAAS), 36, 3.78% American Association for the Advancement of Science (AAAS) 36 publications, 3.78%
Frontiers Media S.A.	Frontiers Media S.A., 36, 3.78% Frontiers Media S.A. 36 publications, 3.78%
Taylor & Francis	Taylor & Francis, 22, 2.31% Taylor & Francis 22 publications, 2.31%
Public Library of Science (PLoS)	Public Library of Science (PLoS), 21, 2.2% Public Library of Science (PLoS) 21 publications, 2.2%
American Society for Microbiology	American Society for Microbiology, 21, 2.2% American Society for Microbiology 21 publications, 2.2%
American Chemical Society (ACS)	American Chemical Society (ACS), 21, 2.2% American Chemical Society (ACS) 21 publications, 2.2%
Oxford University Press	Oxford University Press, 19, 1.99% Oxford University Press 19 publications, 1.99%
Proceedings of the National Academy of Sciences (PNAS)	Proceedings of the National Academy of Sciences (PNAS), 11, 1.15% Proceedings of the National Academy of Sciences (PNAS) 11 publications, 1.15%
American Society for Clinical Investigation	American Society for Clinical Investigation, 6, 0.63% American Society for Clinical Investigation 6 publications, 0.63%
Rockefeller University Press	Rockefeller University Press, 4, 0.42% Rockefeller University Press 4 publications, 0.42%
The American Association of Immunologists	The American Association of Immunologists, 3, 0.31% The American Association of Immunologists 3 publications, 0.31%
Wolters Kluwer Health	Wolters Kluwer Health, 3, 0.31% Wolters Kluwer Health 3 publications, 0.31%
eLife Sciences Publications	eLife Sciences Publications, 3, 0.31% eLife Sciences Publications 3 publications, 0.31%
Bentham Science	Bentham Science, 2, 0.21% Bentham Science 2 publications, 0.21%
Mary Ann Liebert	Mary Ann Liebert, 2, 0.21% Mary Ann Liebert 2 publications, 0.21%
NEJM Group	NEJM Group, 2, 0.21% NEJM Group 2 publications, 0.21%
KeAi Communications Co.	KeAi Communications Co., 2, 0.21% KeAi Communications Co. 2 publications, 0.21%
American Physiological Society	American Physiological Society, 2, 0.21% American Physiological Society 2 publications, 0.21%
Annual Reviews	Annual Reviews, 2, 0.21% Annual Reviews 2 publications, 0.21%
Central Research Institute for Epidemiology	Central Research Institute for Epidemiology, 1, 0.1% Central Research Institute for Epidemiology 1 publication, 0.1%
American Society for Pharmacology and Experimental Therapeutics	American Society for Pharmacology and Experimental Therapeutics, 1, 0.1% American Society for Pharmacology and Experimental Therapeutics 1 publication, 0.1%
The Company of Biologists	The Company of Biologists, 1, 0.1% The Company of Biologists 1 publication, 0.1%
IOS Press	IOS Press, 1, 0.1% IOS Press 1 publication, 0.1%
Baishideng Publishing Group	Baishideng Publishing Group, 1, 0.1% Baishideng Publishing Group 1 publication, 0.1%
	50 100 150 200 250

We do not take into account publications without a DOI.
Statistics recalculated only for publications connected to researchers, organizations and labs registered on the platform.
Statistics recalculated weekly.

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Zost S. J. et al. Potently neutralizing and protective human antibodies against SARS-CoV-2 // Nature. 2020. Vol. 584. No. 7821. pp. 443-449.

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Zost S. J. et al. Potently neutralizing and protective human antibodies against SARS-CoV-2 // Nature. 2020. Vol. 584. No. 7821. pp. 443-449.

RIS |

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RIS Copy

TY - JOUR

DO - 10.1038/s41586-020-2548-6

UR - https://www.nature.com/articles/s41586-020-2548-6

TI - Potently neutralizing and protective human antibodies against SARS-CoV-2

T2 - Nature

AU - Zost, Seth J.

AU - Gilchuk, Pavlo

AU - Case, James B.

AU - Binshtein, Elad

AU - Chen, Rita E.

AU - Nkolola, Joseph P

AU - Schäfer, Alexandra

AU - Reidy, Joseph X

AU - Trivette, Andrew

AU - Nargi, Rachel S.

AU - Sutton, Rachel E.

AU - Suryadevara, Naveenchandra

AU - Martinez, David R.

AU - Williamson, Lauren E

AU - Chen, Elaine C.

AU - Jones, Taylor

AU - Day, Samuel

AU - Myers, Luke

AU - Hassan, Ahmed O.

AU - Kafai, Natasha M.

AU - Winkler, Emma S

AU - Fox, Julie M.

AU - Shrihari, Swathi

AU - Mueller, Benjamin K

AU - Meiler, Jens

AU - Chandrashekar, Abishek

AU - Mercado, Noe B.

AU - Steinhardt, James J

AU - Ren, Kuishu

AU - Loo, Yueh-Ming

AU - Kallewaard, Nicole L.

AU - Mccune, Broc T

AU - Keeler, Shamus P.

AU - HOLTZMAN, Michael J.

AU - Barouch, Dan H.

AU - Gralinski, Lisa E.

AU - Baric, Ralph S

AU - Thackray, Larissa B

AU - Diamond, Michael S.

AU - Carnahan, Robert H.

AU - Crowe, James

PY - 2020

DA - 2020/07/15 00:00:00

PB - Springer Nature

SP - 443-449

IS - 7821

VL - 584

PMID - 32668443

SN - 0028-0836

SN - 1476-4687

ER -

BibTex |

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BibTex Copy

@article{2020_Zost,

author = {Seth J. Zost and Pavlo Gilchuk and James B. Case and Elad Binshtein and Rita E. Chen and Joseph P Nkolola and Alexandra Schäfer and Joseph X Reidy and Andrew Trivette and Rachel S. Nargi and Rachel E. Sutton and Naveenchandra Suryadevara and David R. Martinez and Lauren E Williamson and Elaine C. Chen and Taylor Jones and Samuel Day and Luke Myers and Ahmed O. Hassan and Natasha M. Kafai and Emma S Winkler and Julie M. Fox and Swathi Shrihari and Benjamin K Mueller and Jens Meiler and Abishek Chandrashekar and Noe B. Mercado and James J Steinhardt and Kuishu Ren and Yueh-Ming Loo and Nicole L. Kallewaard and Broc T Mccune and Shamus P. Keeler and Michael J. HOLTZMAN and Dan H. Barouch and Lisa E. Gralinski and Ralph S Baric and Larissa B Thackray and Michael S. Diamond and Robert H. Carnahan and James Crowe},

title = {Potently neutralizing and protective human antibodies against SARS-CoV-2},

journal = {Nature},

year = {2020},

volume = {584},

publisher = {Springer Nature},

month = {jul},

url = {https://www.nature.com/articles/s41586-020-2548-6},

number = {7821},

pages = {443--449},

doi = {10.1038/s41586-020-2548-6}

}

MLA

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MLA Copy

Zost, Seth J., et al. “Potently neutralizing and protective human antibodies against SARS-CoV-2.” Nature, vol. 584, no. 7821, Jul. 2020, pp. 443-449. https://www.nature.com/articles/s41586-020-2548-6.

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Springer Nature

Journal

Nature

Quartile SCImago

Quartile WOS

Impact factor

64.8

ISSN

00280836 (Print)
14764687 (Electronic)

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