Sites of vulnerability in SARS-CoV-2 Antibodies that neutralize severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could be an important tool in treating coronavirus disease 2019 (COVID-19). Brouwer et al. isolated 403 monoclonal antibodies from three convalescent COVID-19 patients. They show that the patients had strong immune responses against the viral spike protein, a complex that binds to receptors on the host cell. A subset of antibodies was able to neutralize the virus. Competition and electron microscopy studies showed that these antibodies target diverse epitopes on the spike, with the two most potent targeting the domain that binds the host receptor. Science , this issue p. 643 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.
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