Potent neutralizing antibodies from COVID-19 patients define multiple targets of vulnerability

Philip J M Brouwer; Tom G Caniels; Karlijn van der Straten; Jonne L Snitselaar; Yoann Aldon; Sandhya Bangaru; Jonathan L Torres; Nisreen M A Okba; Mathieu Claireaux; Gius Kerster; Arthur E H Bentlage; Marlies M van Haaren; Denise Guerra; Judith A Burger; Edith E Schermer; Kirsten D Verheul; Niels van der Velde; Alex van der Kooi; Jelle van Schooten; Mariëlle J van Breemen; Tom P L Bijl; Kwinten Sliepen; Aafke Aartse; Ronald Derking; Ilja Bontjer; Neeltje A Kootstra; W Joost Wiersinga; Gestur Vidarsson; Bart L Haagmans; Andrew B Ward; Godelieve J de Bree; Rogier W Sanders; Marit J van Gils

doi:10.1126/science.abc5902

Potent neutralizing antibodies from COVID-19 patients define multiple targets of vulnerability

Philip J M Brouwer, Tom G Caniels, Karlijn van der Straten, Jonne L Snitselaar, Yoann Aldon, Sandhya Bangaru, Jonathan L Torres, Nisreen M A Okba, Mathieu Claireaux, Gius Kerster, Arthur E H Bentlage, Marlies M van Haaren, Denise Guerra, Judith A Burger, Edith E Schermer, Kirsten D Verheul, Niels van der Velde, Alex van der Kooi, Jelle van Schooten, Mariëlle J van BreemenTom P L Bijl, Kwinten Sliepen, Aafke Aartse, Ronald Derking, Ilja Bontjer, Neeltje A Kootstra, W Joost Wiersinga, Gestur Vidarsson, Bart L Haagmans, Andrew B Ward, Godelieve J de Bree, Rogier W Sanders, Marit J van Gils

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

The rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has had a large impact on global health, travel, and economy. Therefore, preventative and therapeutic measures are urgently needed. Here, we isolated monoclonal antibodies from three convalescent coronavirus disease 2019 (COVID-19) patients using a SARS-CoV-2 stabilized prefusion spike protein. These antibodies had low levels of somatic hypermutation and showed a strong enrichment in VH1-69, VH3-30-3, and VH1-24 gene usage. A subset of the antibodies was able to potently inhibit authentic SARS-CoV-2 infection at a concentration as low as 0.007 micrograms per milliliter. Competition and electron microscopy studies illustrate that the SARS-CoV-2 spike protein contains multiple distinct antigenic sites, including several receptor-binding domain (RBD) epitopes as well as non-RBD epitopes. In addition to providing guidance for vaccine design, the antibodies described here are promising candidates for COVID-19 treatment and prevention.

Original language	English
Pages (from-to)	643-650
Number of pages	8
Journal	Science (New York, N.Y.)
Volume	369
Issue number	6504
DOIs	https://doi.org/10.1126/science.abc5902
Publication status	Published - 7 Aug 2020
Externally published	Yes

Keywords

Adult
Aged
Antibodies, Monoclonal/immunology
Antibodies, Neutralizing/blood
Antibodies, Viral/blood
Antibody Affinity
Antigens, Viral/immunology
B-Lymphocyte Subsets/immunology
Betacoronavirus/immunology
Broadly Neutralizing Antibodies/immunology
COVID-19
Cell Line, Tumor
Coronavirus Infections/immunology
Epitopes/immunology
Female
Humans
Immunologic Memory
Immunophenotyping
Male
Middle Aged
Pandemics/prevention & control
Pneumonia, Viral/immunology
Protein Domains
Protein Interaction Domains and Motifs/immunology
Receptors, Coronavirus
Receptors, Virus/metabolism
SARS-CoV-2
Spike Glycoprotein, Coronavirus/chemistry

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10.1126/science.abc5902

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Brouwer, P. J. M., Caniels, T. G., van der Straten, K., Snitselaar, J. L., Aldon, Y., Bangaru, S., Torres, J. L., Okba, N. M. A., Claireaux, M., Kerster, G., Bentlage, A. E. H., van Haaren, M. M., Guerra, D., Burger, J. A., Schermer, E. E., Verheul, K. D., van der Velde, N., van der Kooi, A., van Schooten, J., ... van Gils, M. J. (2020). Potent neutralizing antibodies from COVID-19 patients define multiple targets of vulnerability. Science (New York, N.Y.), 369(6504), 643-650. https://doi.org/10.1126/science.abc5902

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title = "Potent neutralizing antibodies from COVID-19 patients define multiple targets of vulnerability",

abstract = "The rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has had a large impact on global health, travel, and economy. Therefore, preventative and therapeutic measures are urgently needed. Here, we isolated monoclonal antibodies from three convalescent coronavirus disease 2019 (COVID-19) patients using a SARS-CoV-2 stabilized prefusion spike protein. These antibodies had low levels of somatic hypermutation and showed a strong enrichment in VH1-69, VH3-30-3, and VH1-24 gene usage. A subset of the antibodies was able to potently inhibit authentic SARS-CoV-2 infection at a concentration as low as 0.007 micrograms per milliliter. Competition and electron microscopy studies illustrate that the SARS-CoV-2 spike protein contains multiple distinct antigenic sites, including several receptor-binding domain (RBD) epitopes as well as non-RBD epitopes. In addition to providing guidance for vaccine design, the antibodies described here are promising candidates for COVID-19 treatment and prevention.",

keywords = "Adult, Aged, Antibodies, Monoclonal/immunology, Antibodies, Neutralizing/blood, Antibodies, Viral/blood, Antibody Affinity, Antigens, Viral/immunology, B-Lymphocyte Subsets/immunology, Betacoronavirus/immunology, Broadly Neutralizing Antibodies/immunology, COVID-19, Cell Line, Tumor, Coronavirus Infections/immunology, Epitopes/immunology, Female, Humans, Immunologic Memory, Immunophenotyping, Male, Middle Aged, Pandemics/prevention & control, Pneumonia, Viral/immunology, Protein Domains, Protein Interaction Domains and Motifs/immunology, Receptors, Coronavirus, Receptors, Virus/metabolism, SARS-CoV-2, Spike Glycoprotein, Coronavirus/chemistry",

author = "Brouwer, {Philip J M} and Caniels, {Tom G} and {van der Straten}, Karlijn and Snitselaar, {Jonne L} and Yoann Aldon and Sandhya Bangaru and Torres, {Jonathan L} and Okba, {Nisreen M A} and Mathieu Claireaux and Gius Kerster and Bentlage, {Arthur E H} and {van Haaren}, {Marlies M} and Denise Guerra and Burger, {Judith A} and Schermer, {Edith E} and Verheul, {Kirsten D} and {van der Velde}, Niels and {van der Kooi}, Alex and {van Schooten}, Jelle and {van Breemen}, {Mari{\"e}lle J} and Bijl, {Tom P L} and Kwinten Sliepen and Aafke Aartse and Ronald Derking and Ilja Bontjer and Kootstra, {Neeltje A} and Wiersinga, {W Joost} and Gestur Vidarsson and Haagmans, {Bart L} and Ward, {Andrew B} and {de Bree}, {Godelieve J} and Sanders, {Rogier W} and {van Gils}, {Marit J}",

note = "Copyright {\textcopyright} 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.",

year = "2020",

month = aug,

day = "7",

doi = "10.1126/science.abc5902",

language = "English",

volume = "369",

pages = "643--650",

journal = "Science (New York, N.Y.)",

issn = "0036-8075",

publisher = "American Association for the Advancement of Science",

number = "6504",

}

Brouwer, PJM, Caniels, TG, van der Straten, K, Snitselaar, JL, Aldon, Y, Bangaru, S, Torres, JL, Okba, NMA, Claireaux, M, Kerster, G, Bentlage, AEH, van Haaren, MM, Guerra, D, Burger, JA, Schermer, EE, Verheul, KD, van der Velde, N, van der Kooi, A, van Schooten, J, van Breemen, MJ, Bijl, TPL, Sliepen, K, Aartse, A, Derking, R, Bontjer, I, Kootstra, NA, Wiersinga, WJ, Vidarsson, G, Haagmans, BL, Ward, AB, de Bree, GJ, Sanders, RW & van Gils, MJ 2020, 'Potent neutralizing antibodies from COVID-19 patients define multiple targets of vulnerability', Science (New York, N.Y.), vol. 369, no. 6504, pp. 643-650. https://doi.org/10.1126/science.abc5902

TY - JOUR

T1 - Potent neutralizing antibodies from COVID-19 patients define multiple targets of vulnerability

AU - Brouwer, Philip J M

AU - Caniels, Tom G

AU - van der Straten, Karlijn

AU - Snitselaar, Jonne L

AU - Aldon, Yoann

AU - Bangaru, Sandhya

AU - Torres, Jonathan L

AU - Okba, Nisreen M A

AU - Claireaux, Mathieu

AU - Kerster, Gius

AU - Bentlage, Arthur E H

AU - van Haaren, Marlies M

AU - Guerra, Denise

AU - Burger, Judith A

AU - Schermer, Edith E

AU - Verheul, Kirsten D

AU - van der Velde, Niels

AU - van der Kooi, Alex

AU - van Schooten, Jelle

AU - van Breemen, Mariëlle J

AU - Bijl, Tom P L

AU - Sliepen, Kwinten

AU - Aartse, Aafke

AU - Derking, Ronald

AU - Bontjer, Ilja

AU - Kootstra, Neeltje A

AU - Wiersinga, W Joost

AU - Vidarsson, Gestur

AU - Haagmans, Bart L

AU - Ward, Andrew B

AU - de Bree, Godelieve J

AU - Sanders, Rogier W

AU - van Gils, Marit J

PY - 2020/8/7

Y1 - 2020/8/7

N2 - The rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has had a large impact on global health, travel, and economy. Therefore, preventative and therapeutic measures are urgently needed. Here, we isolated monoclonal antibodies from three convalescent coronavirus disease 2019 (COVID-19) patients using a SARS-CoV-2 stabilized prefusion spike protein. These antibodies had low levels of somatic hypermutation and showed a strong enrichment in VH1-69, VH3-30-3, and VH1-24 gene usage. A subset of the antibodies was able to potently inhibit authentic SARS-CoV-2 infection at a concentration as low as 0.007 micrograms per milliliter. Competition and electron microscopy studies illustrate that the SARS-CoV-2 spike protein contains multiple distinct antigenic sites, including several receptor-binding domain (RBD) epitopes as well as non-RBD epitopes. In addition to providing guidance for vaccine design, the antibodies described here are promising candidates for COVID-19 treatment and prevention.

AB - The rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has had a large impact on global health, travel, and economy. Therefore, preventative and therapeutic measures are urgently needed. Here, we isolated monoclonal antibodies from three convalescent coronavirus disease 2019 (COVID-19) patients using a SARS-CoV-2 stabilized prefusion spike protein. These antibodies had low levels of somatic hypermutation and showed a strong enrichment in VH1-69, VH3-30-3, and VH1-24 gene usage. A subset of the antibodies was able to potently inhibit authentic SARS-CoV-2 infection at a concentration as low as 0.007 micrograms per milliliter. Competition and electron microscopy studies illustrate that the SARS-CoV-2 spike protein contains multiple distinct antigenic sites, including several receptor-binding domain (RBD) epitopes as well as non-RBD epitopes. In addition to providing guidance for vaccine design, the antibodies described here are promising candidates for COVID-19 treatment and prevention.

KW - Adult

KW - Aged

KW - Antibodies, Monoclonal/immunology

KW - Antibodies, Neutralizing/blood

KW - Antibodies, Viral/blood

KW - Antibody Affinity

KW - Antigens, Viral/immunology

KW - B-Lymphocyte Subsets/immunology

KW - Betacoronavirus/immunology

KW - Broadly Neutralizing Antibodies/immunology

KW - COVID-19

KW - Cell Line, Tumor

KW - Coronavirus Infections/immunology

KW - Epitopes/immunology

KW - Female

KW - Humans

KW - Immunologic Memory

KW - Immunophenotyping

KW - Male

KW - Middle Aged

KW - Pandemics/prevention & control

KW - Pneumonia, Viral/immunology

KW - Protein Domains

KW - Protein Interaction Domains and Motifs/immunology

KW - Receptors, Coronavirus

KW - Receptors, Virus/metabolism

KW - SARS-CoV-2

KW - Spike Glycoprotein, Coronavirus/chemistry

U2 - 10.1126/science.abc5902

DO - 10.1126/science.abc5902

M3 - Article

C2 - 32540902

SN - 0036-8075

VL - 369

SP - 643

EP - 650

JO - Science (New York, N.Y.)

JF - Science (New York, N.Y.)

IS - 6504

ER -

Potent neutralizing antibodies from COVID-19 patients define multiple targets of vulnerability

Abstract

Keywords

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