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

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

Science, Vol.369, No.6504, 643-+, 2020

DOI10.1126/science.abc5902 Export Citation

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

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

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 (tow 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.