Cell Reports (Jul 2021)
Isolation and characterization of cross-neutralizing coronavirus antibodies from COVID-19+ subjects
- Madeleine F. Jennewein,
- Anna J. MacCamy,
- Nicholas R. Akins,
- Junli Feng,
- Leah J. Homad,
- Nicholas K. Hurlburt,
- Emilie Seydoux,
- Yu-Hsin Wan,
- Andrew B. Stuart,
- Venkata Viswanadh Edara,
- Katharine Floyd,
- Abigail Vanderheiden,
- John R. Mascola,
- Nicole Doria-Rose,
- Lingshu Wang,
- Eun Sung Yang,
- Helen Y. Chu,
- Jonathan L. Torres,
- Gabriel Ozorowski,
- Andrew B. Ward,
- Rachael E. Whaley,
- Kristen W. Cohen,
- Marie Pancera,
- M. Juliana McElrath,
- Janet A. Englund,
- Andrés Finzi,
- Mehul S. Suthar,
- Andrew T. McGuire,
- Leonidas Stamatatos
Affiliations
- Madeleine F. Jennewein
- Fred Hutchinson Cancer Research Center, Vaccines and Infectious Disease Division, Seattle, WA 98109, USA
- Anna J. MacCamy
- Fred Hutchinson Cancer Research Center, Vaccines and Infectious Disease Division, Seattle, WA 98109, USA
- Nicholas R. Akins
- Fred Hutchinson Cancer Research Center, Vaccines and Infectious Disease Division, Seattle, WA 98109, USA
- Junli Feng
- Fred Hutchinson Cancer Research Center, Vaccines and Infectious Disease Division, Seattle, WA 98109, USA
- Leah J. Homad
- Fred Hutchinson Cancer Research Center, Vaccines and Infectious Disease Division, Seattle, WA 98109, USA
- Nicholas K. Hurlburt
- Fred Hutchinson Cancer Research Center, Vaccines and Infectious Disease Division, Seattle, WA 98109, USA
- Emilie Seydoux
- Fred Hutchinson Cancer Research Center, Vaccines and Infectious Disease Division, Seattle, WA 98109, USA
- Yu-Hsin Wan
- Fred Hutchinson Cancer Research Center, Vaccines and Infectious Disease Division, Seattle, WA 98109, USA
- Andrew B. Stuart
- Fred Hutchinson Cancer Research Center, Vaccines and Infectious Disease Division, Seattle, WA 98109, USA
- Venkata Viswanadh Edara
- Center for Childhood Infections and Vaccines of Children’s Healthcare of Atlanta, Department of Pediatrics, Emory University School of Medicine, Emory Vaccine Center, Yerkes National Primate Research Center, Atlanta, GA 30322, USA
- Katharine Floyd
- Center for Childhood Infections and Vaccines of Children’s Healthcare of Atlanta, Department of Pediatrics, Emory University School of Medicine, Emory Vaccine Center, Yerkes National Primate Research Center, Atlanta, GA 30322, USA
- Abigail Vanderheiden
- Center for Childhood Infections and Vaccines of Children’s Healthcare of Atlanta, Department of Pediatrics, Emory University School of Medicine, Emory Vaccine Center, Yerkes National Primate Research Center, Atlanta, GA 30322, USA
- John R. Mascola
- Vaccine Research Center, NIAID, NIH, Bethesda, MD 20892, USA
- Nicole Doria-Rose
- Vaccine Research Center, NIAID, NIH, Bethesda, MD 20892, USA
- Lingshu Wang
- Vaccine Research Center, NIAID, NIH, Bethesda, MD 20892, USA
- Eun Sung Yang
- Vaccine Research Center, NIAID, NIH, Bethesda, MD 20892, USA
- Helen Y. Chu
- University of Washington, Department of Medicine, Seattle, WA 98109, USA
- Jonathan L. Torres
- Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
- Gabriel Ozorowski
- Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
- Andrew B. Ward
- Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
- Rachael E. Whaley
- Fred Hutchinson Cancer Research Center, Vaccines and Infectious Disease Division, Seattle, WA 98109, USA
- Kristen W. Cohen
- Fred Hutchinson Cancer Research Center, Vaccines and Infectious Disease Division, Seattle, WA 98109, USA
- Marie Pancera
- Fred Hutchinson Cancer Research Center, Vaccines and Infectious Disease Division, Seattle, WA 98109, USA; Vaccine Research Center, NIAID, NIH, Bethesda, MD 20892, USA
- M. Juliana McElrath
- Fred Hutchinson Cancer Research Center, Vaccines and Infectious Disease Division, Seattle, WA 98109, USA; University of Washington, Department of Medicine, Seattle, WA 98109, USA; University of Washington, Department of Global Health, Seattle, WA 98109, USA
- Janet A. Englund
- Department of Pediatrics, University of Washington and Seattle Children’s Research Institute, Seattle, WA 98109, USA
- Andrés Finzi
- Université de Montréal, Montreal, QC, Canada
- Mehul S. Suthar
- Center for Childhood Infections and Vaccines of Children’s Healthcare of Atlanta, Department of Pediatrics, Emory University School of Medicine, Emory Vaccine Center, Yerkes National Primate Research Center, Atlanta, GA 30322, USA; Corresponding author
- Andrew T. McGuire
- Fred Hutchinson Cancer Research Center, Vaccines and Infectious Disease Division, Seattle, WA 98109, USA; University of Washington, Department of Global Health, Seattle, WA 98109, USA; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA 98195, USA; Corresponding author
- Leonidas Stamatatos
- Fred Hutchinson Cancer Research Center, Vaccines and Infectious Disease Division, Seattle, WA 98109, USA; University of Washington, Department of Global Health, Seattle, WA 98109, USA; Corresponding author
- Journal volume & issue
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Vol. 36,
no. 2
p. 109353
Abstract
Summary: SARS-CoV-2 is one of three coronaviruses that have crossed the animal-to-human barrier and caused widespread disease in the past two decades. The development of a universal human coronavirus vaccine could prevent future pandemics. We characterize 198 antibodies isolated from four COVID-19+ subjects and identify 14 SARS-CoV-2 neutralizing antibodies. One targets the N-terminal domain (NTD), one recognizes an epitope in S2, and 11 bind the receptor-binding domain (RBD). Three anti-RBD neutralizing antibodies cross-neutralize SARS-CoV-1 by effectively blocking binding of both the SARS-CoV-1 and SARS-CoV-2 RBDs to the ACE2 receptor. Using the K18-hACE transgenic mouse model, we demonstrate that the neutralization potency and antibody epitope specificity regulates the in vivo protective potential of anti-SARS-CoV-2 antibodies. All four cross-neutralizing antibodies neutralize the B.1.351 mutant strain. Thus, our study reveals that epitopes in S2 can serve as blueprints for the design of immunogens capable of eliciting cross-neutralizing coronavirus antibodies.
