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Potent neutralizing antibodies from COVID-19 patients define multiple targets of vulnerability.
Science. 2020 08 07; 369(6504):643-650.Sci

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.

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Authors+Show Affiliations

Brouwer PJM
Department of Medical Microbiology, Amsterdam UMC, University of Amsterdam, Amsterdam Institute for Infection and Immunity, 1105AZ Amsterdam, Netherlands.
Caniels TG
Department of Medical Microbiology, Amsterdam UMC, University of Amsterdam, Amsterdam Institute for Infection and Immunity, 1105AZ Amsterdam, Netherlands.
van der Straten K
Department of Medical Microbiology, Amsterdam UMC, University of Amsterdam, Amsterdam Institute for Infection and Immunity, 1105AZ Amsterdam, Netherlands. Department of Internal Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam Institute for Infection and Immunity, 1105AZ Amsterdam, Netherlands.
Snitselaar JL
Department of Medical Microbiology, Amsterdam UMC, University of Amsterdam, Amsterdam Institute for Infection and Immunity, 1105AZ Amsterdam, Netherlands.
Aldon Y
Department of Medical Microbiology, Amsterdam UMC, University of Amsterdam, Amsterdam Institute for Infection and Immunity, 1105AZ Amsterdam, Netherlands.
Bangaru S
Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Torres JL
Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Okba NMA
Department of Viroscience, Erasmus Medical Center, Rotterdam, 3015GD, Netherlands.
Claireaux M
Department of Medical Microbiology, Amsterdam UMC, University of Amsterdam, Amsterdam Institute for Infection and Immunity, 1105AZ Amsterdam, Netherlands.
Kerster G
Department of Medical Microbiology, Amsterdam UMC, University of Amsterdam, Amsterdam Institute for Infection and Immunity, 1105AZ Amsterdam, Netherlands.
Bentlage AEH
Sanquin Research, Department of Experimental Immunohematology, Amsterdam, Netherlands and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, 1006AD Amsterdam, Netherlands.
van Haaren MM
Department of Medical Microbiology, Amsterdam UMC, University of Amsterdam, Amsterdam Institute for Infection and Immunity, 1105AZ Amsterdam, Netherlands.
Guerra D
Department of Medical Microbiology, Amsterdam UMC, University of Amsterdam, Amsterdam Institute for Infection and Immunity, 1105AZ Amsterdam, Netherlands.
Burger JA
Department of Medical Microbiology, Amsterdam UMC, University of Amsterdam, Amsterdam Institute for Infection and Immunity, 1105AZ Amsterdam, Netherlands.
Schermer EE
Department of Medical Microbiology, Amsterdam UMC, University of Amsterdam, Amsterdam Institute for Infection and Immunity, 1105AZ Amsterdam, Netherlands.
Verheul KD
Department of Medical Microbiology, Amsterdam UMC, University of Amsterdam, Amsterdam Institute for Infection and Immunity, 1105AZ Amsterdam, Netherlands.
van der Velde N
IBIS Technologies BV, 7521PR Enschede, Netherlands.
van der Kooi A
IBIS Technologies BV, 7521PR Enschede, Netherlands.
van Schooten J
Department of Medical Microbiology, Amsterdam UMC, University of Amsterdam, Amsterdam Institute for Infection and Immunity, 1105AZ Amsterdam, Netherlands.
van Breemen MJ
Department of Medical Microbiology, Amsterdam UMC, University of Amsterdam, Amsterdam Institute for Infection and Immunity, 1105AZ Amsterdam, Netherlands.
Bijl TPL
Department of Medical Microbiology, Amsterdam UMC, University of Amsterdam, Amsterdam Institute for Infection and Immunity, 1105AZ Amsterdam, Netherlands.
Sliepen K
Department of Medical Microbiology, Amsterdam UMC, University of Amsterdam, Amsterdam Institute for Infection and Immunity, 1105AZ Amsterdam, Netherlands.
Aartse A
Department of Medical Microbiology, Amsterdam UMC, University of Amsterdam, Amsterdam Institute for Infection and Immunity, 1105AZ Amsterdam, Netherlands. Department of Virology, Biomedical Primate Research Centre, 2288GJ Rijswijk, Netherlands.
Derking R
Department of Medical Microbiology, Amsterdam UMC, University of Amsterdam, Amsterdam Institute for Infection and Immunity, 1105AZ Amsterdam, Netherlands.
Bontjer I
Department of Medical Microbiology, Amsterdam UMC, University of Amsterdam, Amsterdam Institute for Infection and Immunity, 1105AZ Amsterdam, Netherlands.
Kootstra NA
Department of Experimental Immunology, Amsterdam UMC, University of Amsterdam, Amsterdam Institute for Infection and Immunity, 1105AZ Amsterdam, Netherlands.
Wiersinga WJ
Department of Internal Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam Institute for Infection and Immunity, 1105AZ Amsterdam, Netherlands.
Vidarsson G
Sanquin Research, Department of Experimental Immunohematology, Amsterdam, Netherlands and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, 1006AD Amsterdam, Netherlands.
Haagmans BL
Department of Viroscience, Erasmus Medical Center, Rotterdam, 3015GD, Netherlands.
Ward AB
Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
de Bree GJ
Department of Internal Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam Institute for Infection and Immunity, 1105AZ Amsterdam, Netherlands. m.j.vangils@amsterdamumc.nl r.w.sanders@amsterdamumc.nl g.j.debree@amsterdamumc.nl.
Sanders RW
Department of Medical Microbiology, Amsterdam UMC, University of Amsterdam, Amsterdam Institute for Infection and Immunity, 1105AZ Amsterdam, Netherlands. m.j.vangils@amsterdamumc.nl r.w.sanders@amsterdamumc.nl g.j.debree@amsterdamumc.nl. Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY 10021, USA.
van Gils MJ
Department of Medical Microbiology, Amsterdam UMC, University of Amsterdam, Amsterdam Institute for Infection and Immunity, 1105AZ Amsterdam, Netherlands. m.j.vangils@amsterdamumc.nl r.w.sanders@amsterdamumc.nl g.j.debree@amsterdamumc.nl.

MeSH

AdultAgedAntibodies, MonoclonalAntibodies, NeutralizingAntibodies, ViralAntibody AffinityAntigens, ViralB-Lymphocyte SubsetsBetacoronavirusBroadly Neutralizing AntibodiesCOVID-19Cell Line, TumorCoronavirus InfectionsEpitopesFemaleHumansImmunologic MemoryImmunophenotypingMaleMiddle AgedPandemicsPneumonia, ViralProtein DomainsProtein Interaction Domains and MotifsReceptors, CoronavirusReceptors, VirusSARS-CoV-2Spike Glycoprotein, Coronavirus

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

32540902

Citation

Brouwer, Philip J M., et al. "Potent Neutralizing Antibodies From COVID-19 Patients Define Multiple Targets of Vulnerability." Science (New York, N.Y.), vol. 369, no. 6504, 2020, pp. 643-650.
Brouwer PJM, Caniels TG, van der Straten K, et al. Potent neutralizing antibodies from COVID-19 patients define multiple targets of vulnerability. Science. 2020;369(6504):643-650.
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
Brouwer PJM, et al. Potent Neutralizing Antibodies From COVID-19 Patients Define Multiple Targets of Vulnerability. Science. 2020 08 7;369(6504):643-650. PubMed PMID: 32540902.
* Article titles in AMA citation format should be in sentence-case
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, Y1 - 2020/06/15/ PY - 2020/05/04/received PY - 2020/06/10/accepted PY - 2020/6/17/pubmed PY - 2020/8/25/medline PY - 2020/6/17/entrez SP - 643 EP - 650 JF - Science (New York, N.Y.) JO - Science VL - 369 IS - 6504 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. SN - 1095-9203 UR - https://www.unboundmedicine.com/medline/citation/32540902/Potent_neutralizing_antibodies_from_COVID_19_patients_define_multiple_targets_of_vulnerability_ DB - PRIME DP - Unbound Medicine ER -