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Isolation of potent SARS-CoV-2 neutralizing antibodies and protection from disease in a small animal model

2020; American Association for the Advancement of Science; Volume: 369; Issue: 6506 Linguagem: Inglês

10.1126/science.abc7520

1095-9203

Thomas F. Rogers, Fangzhu Zhao, Deli Huang, Nathan Beutler, Alison Burns, Wanting He, Oliver Limbo, Chloe N. Smith, Ge Song, Jordan L. Woehl, Linlin Yang, Robert Abbott, Sean Callaghan, Elijah Garcia, Jonathan Hurtado, Mara Parren, Linghang Peng, Sydney I. Ramirez, James Ricketts, Michael J. Ricciardi, Stephen A. Rawlings, Nicholas C. Wu, Meng Yuan, Davey M. Smith, David Nemazee, John R. Teijaro, James E. Voss, Ian A. Wilson, Raiees Andrabi, Bryan Briney, Elise Landais, Devin Sok, Joseph G. Jardine, Dennis R. Burton,

Viral gastroenteritis research and epidemiology

Countermeasures to prevent and treat coronavirus disease 2019 (COVID-19) are a global health priority. We enrolled a cohort of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-recovered participants, developed neutralization assays to investigate antibody responses, adapted our high-throughput antibody generation pipeline to rapidly screen more than 1800 antibodies, and established an animal model to test protection. We isolated potent neutralizing antibodies (nAbs) to two epitopes on the receptor binding domain (RBD) and to distinct non-RBD epitopes on the spike (S) protein. As indicated by maintained weight and low lung viral titers in treated animals, the passive transfer of a nAb provides protection against disease in high-dose SARS-CoV-2 challenge in Syrian hamsters. The study suggests a role for nAbs in prophylaxis, and potentially therapy, of COVID-19. The nAbs also define protective epitopes to guide vaccine design.