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

American Association for the Advancement of Science (AAAS) - Tập 369 Số 6506 - Trang 956-963 - 2020
Thomas F. Rogers1,2, Fangzhu Zhao3,1,4, Deli Huang1, Nathan Beutler1, Alison Burns3,1,4, Wanting He3,1,4, Oliver Limbo4,5, Chloe N. Smith1,4, Ge Song3,1,4, Jordan L. Woehl4,5, Linlin Yang1, Robert Abbott6,3, Sean Callaghan3,1,4, Elijah Garcia1, Jonathan Hurtado7,3,1, Mara Parren1, Linghang Peng1, Sydney I. Ramirez6, James Ricketts1, Michael J. Ricciardi8, Stephen A. Rawlings2, Nicholas C. Wu9, Meng Yuan9, Davey M. Smith2, David Nemazee1, John R. Teijaro1, James E. Voss1, Ian A. Wilson3,9,4, Raiees Andrabi3,1,4, Bryan Briney7,3,1, Elise Landais3,1,4,5, Devin Sok3,1,4,5, Joseph G. Jardine4,5, Dennis R. Burton3,1,4,10
1Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA
2Division of Infectious Diseases, Department of Medicine, University of California San Diego, La Jolla, CA 92037, USA
3Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA, 92037, USA
4IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA
5IAVI, New York, NY 10004, USA
6Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology (LJI), La Jolla, CA 92037, USA
7Center for Viral Systems Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
8Department of Pathology, George Washington University, Washington, DC 20052, USA.
9Department of Integrative, Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
10Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University, Cambridge, MA 02139, USA

Tóm tắt

Protective neutralizing antibodies Antibodies produced by survivors of coronavirus disease 2019 (COVID-19) may be leveraged to develop therapies. A first step is identifying neutralizing antibodies, which confer strong protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Rogers et al. used a high-throughput pipeline to isolate and characterize monoclonal antibodies from convalescent donors. Antibodies were selected for binding to the viral spike protein, which facilitates entry into host cells by binding to the angiotensin-converting enzyme 2 (ACE2) receptor. Most isolated antibodies bound to regions of the spike outside of the receptor binding domain (RBD); however, a larger proportion of the RBD-binding antibodies were neutralizing, with the most potent binding at a site that overlaps the ACE2 binding site. Two of the neutralizing antibodies were tested in Syrian hamsters and provided protection against SARS-CoV-2 infection. Science , this issue p. 956

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