Tags

Type your tag names separated by a space and hit enter

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.

Authors+Show Affiliations

Department of Medical Microbiology, Amsterdam UMC, University of Amsterdam, Amsterdam Institute for Infection and Immunity, 1105AZ Amsterdam, Netherlands.Department of Medical Microbiology, Amsterdam UMC, University of Amsterdam, Amsterdam Institute for Infection and Immunity, 1105AZ Amsterdam, Netherlands.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.Department of Medical Microbiology, Amsterdam UMC, University of Amsterdam, Amsterdam Institute for Infection and Immunity, 1105AZ Amsterdam, Netherlands.Department of Medical Microbiology, Amsterdam UMC, University of Amsterdam, Amsterdam Institute for Infection and Immunity, 1105AZ Amsterdam, Netherlands.Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.Department of Viroscience, Erasmus Medical Center, Rotterdam, 3015GD, Netherlands.Department of Medical Microbiology, Amsterdam UMC, University of Amsterdam, Amsterdam Institute for Infection and Immunity, 1105AZ Amsterdam, Netherlands.Department of Medical Microbiology, Amsterdam UMC, University of Amsterdam, Amsterdam Institute for Infection and Immunity, 1105AZ Amsterdam, Netherlands.Sanquin Research, Department of Experimental Immunohematology, Amsterdam, Netherlands and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, 1006AD Amsterdam, Netherlands.Department of Medical Microbiology, Amsterdam UMC, University of Amsterdam, Amsterdam Institute for Infection and Immunity, 1105AZ Amsterdam, Netherlands.Department of Medical Microbiology, Amsterdam UMC, University of Amsterdam, Amsterdam Institute for Infection and Immunity, 1105AZ Amsterdam, Netherlands.Department of Medical Microbiology, Amsterdam UMC, University of Amsterdam, Amsterdam Institute for Infection and Immunity, 1105AZ Amsterdam, Netherlands.Department of Medical Microbiology, Amsterdam UMC, University of Amsterdam, Amsterdam Institute for Infection and Immunity, 1105AZ Amsterdam, Netherlands.Department of Medical Microbiology, Amsterdam UMC, University of Amsterdam, Amsterdam Institute for Infection and Immunity, 1105AZ Amsterdam, Netherlands.IBIS Technologies BV, 7521PR Enschede, Netherlands.IBIS Technologies BV, 7521PR Enschede, Netherlands.Department of Medical Microbiology, Amsterdam UMC, University of Amsterdam, Amsterdam Institute for Infection and Immunity, 1105AZ Amsterdam, Netherlands.Department of Medical Microbiology, Amsterdam UMC, University of Amsterdam, Amsterdam Institute for Infection and Immunity, 1105AZ Amsterdam, Netherlands.Department of Medical Microbiology, Amsterdam UMC, University of Amsterdam, Amsterdam Institute for Infection and Immunity, 1105AZ Amsterdam, Netherlands.Department of Medical Microbiology, Amsterdam UMC, University of Amsterdam, Amsterdam Institute for Infection and Immunity, 1105AZ Amsterdam, Netherlands.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.Department of Medical Microbiology, Amsterdam UMC, University of Amsterdam, Amsterdam Institute for Infection and Immunity, 1105AZ Amsterdam, Netherlands.Department of Medical Microbiology, Amsterdam UMC, University of Amsterdam, Amsterdam Institute for Infection and Immunity, 1105AZ Amsterdam, Netherlands.Department of Experimental Immunology, 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.Sanquin Research, Department of Experimental Immunohematology, Amsterdam, Netherlands and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, 1006AD Amsterdam, Netherlands.Department of Viroscience, Erasmus Medical Center, Rotterdam, 3015GD, Netherlands.Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.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.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.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.

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/full_citation L2 - http://www.zgddek.com/EN/abstract/abstract14902.shtml DB - PRIME DP - Unbound Medicine ER -