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

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

The rapid spread of SARS-CoV-2 has a significant impact on global health, travel and economy. Therefore, preventative and therapeutic measures are urgently needed. Here, we isolated monoclonal antibodies from three convalescent 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 were able to potently inhibit authentic SARS-CoV-2 infection as low as 0.007 μg/mL. 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.