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Author Notes:

James E. Crowe, Jr., james.crowe@vumc.org

Conceived of the project: S.J.Z., P.G., R.H.C., L.B.T., M.S.D., J.E.C.; Obtained funding: J.E.C. and M.S.D. Obtained human samples: M.O., H.Y.C., J.E.C.; Performed laboratory experiments: S.J.Z., P.G., R.E.C., J.X.R., A.T., R.S.N., R.E.S., N.S., E.B., J.E.D., K.W.M., S.S., D.R.M, P.W.R., L.-M.B,; Performed computational work: E.C.C., T.J., S.D., L.M.; Supervised research: S.P.J.W. M.S.D., L.B.T., R.S.B., R.H.C., J.E.C. Provided critical reagents: J.E.D., K.W.M., F.-H.L., D.C.N., I.S., R.S.B. Wrote the first draft of the paper: S.J.Z., P.G., R.H.C., J.E.C.; All authors reviewed and approved the final manuscript.

We thank Merissa Mayo and Norma Suazo Galeano for coordination of human subjects studies, David O’Connor, Nasia Safdar, Geoff Baird, Jay Shendure and Samira Mubareka for helpful advice on human subjects, Angela Jones and the staff of the Vanderbilt VANTAGE core laboratory for expedited sequencing, Ross Trosseth for assistance with data management and analysis, Robin Bombardi and Cinque Soto for technical consultation on genomics approaches, Arthur Kim for production of a recombinant form of the mAb CR3022, Chris Swearingen and the staff of Fedex Express Specialty Services for expedited transport services, Vincent Pai and Keith Breinlinger of Berkeley Lights, Inc., and Kevin Louder and scientists at Twist Bioscience, Brian Fritz at 10x Genomics, and representatives at ACEA Biosciences for providing resources, outstanding expedited services and expert applications support.

We thank Andrew Ward, Sandhya Bangaru, Patrick McTamney, Kuishu Ren, and Arnita Barnes for protein reagents. This study was supported by Defense Advanced Research Projects Agency (DARPA) grant HR0011-18-2-0001, NIH contracts 75N93019C00074 and 75N93019C00062 and the Dolly Parton COVID-19 Research Fund at Vanderbilt. This work was supported by NIH grant 1S10RR028106-01A1 for the Next Generation Nucleic Acid Sequencer, housed in Vanderbilt Technologies for Advanced Genomics (VANTAGE) and supported by the National Center for Research Resources, Grant UL1 RR024975-01, and is now at the National Center for Advancing Translational Sciences, Grant 2 UL1 TR000445-06. S.J.Z. was supported by NIH T32 AI095202. J.B.C. is supported by a Helen Hay Whitney Foundation postdoctoral fellowship D.R.M. was supported by NIH T32 AI007151 and a Burroughs Wellcome Fund Postdoctoral Enrichment Program Award. J.E.C. is the recipient of the 2019 Future Insight Prize from Merck KGaA, Darmstadt Germany, which supported this research with a research grant. The content is solely the responsibility of the authors and does not necessarily represent the official views of the U.S. government or the other sponsors.

R.S.B. has served as a consultant for Takeda and Sanofi Pasteur on issues related to vaccines. M.S.D. is a consultant for Inbios, Vir Biotechnology, NGM Biopharmaceuticals, Eli Lilly, and on the Scientific Advisory Board of Moderna, and a recipient of unrelated research grants from Moderna and Emergent BioSolutions. H.Y.C. has served as a consultant for Merck and GlaxoSmithKline, research funding from Sanofi Pasteur and research support from Cepheid, Genentech, and Ellume. J.E.C. has served as a consultant for Sanofi and is on the Scientific Advisory Boards of CompuVax and Meissa Vaccines, is a recipient of previous unrelated research grants from Moderna and Sanofi and is Founder of IDBiologics, Inc. Vanderbilt University has applied for patents concerning SARS-CoV-2 antibodies that are related to this work. Emory University has applied for a patent concerning the plasmablast survival medium. S.P.J.W. and P.W.R. have filed a disclosure with Washington University for the recombinant VSV. J.E.D. and K.W.M. are employees of Berkeley Lights, Inc. All other authors declared no competing interests.

Subjects:

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Biochemistry & Molecular Biology
  • Cell Biology
  • Medicine, Research & Experimental
  • Research & Experimental Medicine
  • RESPIRATORY SYNDROME CORONAVIRUS
  • LENGTH INFECTIOUS CDNA
  • SARS CORONAVIRUS
  • MERS-COV
  • NEUTRALIZING ANTIBODIES
  • POTENT NEUTRALIZATION
  • STRUCTURAL DEFINITION
  • REVERSE GENETICS
  • EPITOPE

Rapid isolation and profiling of a diverse panel of human monoclonal antibodies targeting the SARS-CoV-2 spike protein

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Journal Title:

NATURE MEDICINE

Volume:

Volume 26, Number 9

Publisher:

, Pages 1422-1427

Type of Work:

Article | Post-print: After Peer Review

Abstract:

Antibodies are a principal determinant of immunity for most RNA viruses and have promise to reduce infection or disease during major epidemics. The novel coronavirus SARS-CoV-2 has caused a global pandemic with millions of infections and hundreds of thousands of deaths to date1,2. In response, we used a rapid antibody discovery platform to isolate hundreds of human monoclonal antibodies (mAbs) against the SARS-CoV-2 spike (S) protein. We stratify these mAbs into five major classes on the basis of their reactivity to subdomains of S protein as well as their cross-reactivity to SARS-CoV. Many of these mAbs inhibit infection of authentic SARS-CoV-2 virus, with most neutralizing mAbs recognizing the receptor-binding domain (RBD) of S. This work defines sites of vulnerability on SARS-CoV-2 S and demonstrates the speed and robustness of advanced antibody discovery platforms.
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