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

07 August 2020 Vol 369, Issue 6504


Research Articles
Potent neutralizing antibodies from COVID-19 patients define multiple targets of vulnerability
By 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
Science07 Aug 2020 : 643-650 Open Access
Isolation of 403 monoclonal antibodies from COVID-19 patients revealed convergent gene usage and multiple target epitopes.
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.