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

Thomas F. Rogers, Fangzhu Zhao, Deli Huang, Nathan Beutler, Alison Burns, Wan Ting He, Oliver Limbo, Chloe Smith, Ge Song, Jordan Woehl, Linlin Yang, Robert K. Abbott, Sean Callaghan, Elijah Garcia, Jonathan Hurtado, Mara Parren, Linghang Peng, Sydney Ramirez, James Ricketts, Michael J. RicciardiStephen 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

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)956-963
Number of pages8
JournalScience (New York, N.Y.)
Volume369
Issue number6506
DOIs
StatePublished - Aug 21 2020
Externally publishedYes

Keywords

  • COVID-19
  • severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)

ASJC Scopus subject areas

  • General

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