Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

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, Emily 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, View ORCID ProfileAndrew B. Ward, Rachael E. Whaley, Kristen W. Cohen, Marie Pancera, M. Juliana McElrath, Janet A. Englund, Andrés Finzi, View ORCID ProfileMehul S. Suthar, Andrew T. McGuire, View ORCID ProfileLeonidas Stamatatos
doi: https://doi.org/10.1101/2021.03.23.436684
Madeleine F. Jennewein
1Fred Hutchinson Cancer Research Center, Vaccines and Infectious Disease Division, Seattle, WA, 98109, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Anna J. MacCamy
1Fred Hutchinson Cancer Research Center, Vaccines and Infectious Disease Division, Seattle, WA, 98109, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Nicholas R. Akins
1Fred Hutchinson Cancer Research Center, Vaccines and Infectious Disease Division, Seattle, WA, 98109, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Junli Feng
1Fred Hutchinson Cancer Research Center, Vaccines and Infectious Disease Division, Seattle, WA, 98109, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Leah J. Homad
1Fred Hutchinson Cancer Research Center, Vaccines and Infectious Disease Division, Seattle, WA, 98109, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Nicholas K. Hurlburt
1Fred Hutchinson Cancer Research Center, Vaccines and Infectious Disease Division, Seattle, WA, 98109, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Emily Seydoux
1Fred Hutchinson Cancer Research Center, Vaccines and Infectious Disease Division, Seattle, WA, 98109, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yu-Hsin Wan
1Fred Hutchinson Cancer Research Center, Vaccines and Infectious Disease Division, Seattle, WA, 98109, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Andrew B. Stuart
1Fred Hutchinson Cancer Research Center, Vaccines and Infectious Disease Division, Seattle, WA, 98109, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Venkata Viswanadh Edara
8Center 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
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Katharine Floyd
8Center 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
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Abigail Vanderheiden
8Center 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
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
John R. Mascola
3Vaccine Research Center, NAID, NIH, Bethesda, MD 20892, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Nicole Doria-Rose
3Vaccine Research Center, NAID, NIH, Bethesda, MD 20892, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Lingshu Wang
3Vaccine Research Center, NAID, NIH, Bethesda, MD 20892, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Eun Sung Yang
3Vaccine Research Center, NAID, NIH, Bethesda, MD 20892, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Helen Y. Chu
4University of Washington, Department of Medicine, Seattle, WA 98109, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jonathan L. Torres
2Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, 92037, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Gabriel Ozorowski
2Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, 92037, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Andrew B. Ward
2Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, 92037, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Andrew B. Ward
Rachael E. Whaley
1Fred Hutchinson Cancer Research Center, Vaccines and Infectious Disease Division, Seattle, WA, 98109, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kristen W. Cohen
1Fred Hutchinson Cancer Research Center, Vaccines and Infectious Disease Division, Seattle, WA, 98109, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Marie Pancera
1Fred Hutchinson Cancer Research Center, Vaccines and Infectious Disease Division, Seattle, WA, 98109, USA
3Vaccine Research Center, NAID, NIH, Bethesda, MD 20892, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
M. Juliana McElrath
1Fred Hutchinson Cancer Research Center, Vaccines and Infectious Disease Division, Seattle, WA, 98109, USA
4University of Washington, Department of Medicine, Seattle, WA 98109, USA
5University of Washington, Department of Global Health, Seattle, WA 98109, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Janet A. Englund
6Department of Pediatrics, University of Washington and Seattle Children’s Research Institute, Seattle, WA 98109, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Andrés Finzi
7Université de Montréal, Montreal, QC, Canada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Mehul S. Suthar
8Center 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
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Mehul S. Suthar
  • For correspondence: lstamata@fredhutch.org amcguire@fredhutch.org mehul.s.suthar@emory.edu
Andrew T. McGuire
1Fred Hutchinson Cancer Research Center, Vaccines and Infectious Disease Division, Seattle, WA, 98109, USA
5University of Washington, Department of Global Health, Seattle, WA 98109, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: lstamata@fredhutch.org amcguire@fredhutch.org mehul.s.suthar@emory.edu
Leonidas Stamatatos
1Fred Hutchinson Cancer Research Center, Vaccines and Infectious Disease Division, Seattle, WA, 98109, USA
5University of Washington, Department of Global Health, Seattle, WA 98109, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Leonidas Stamatatos
  • For correspondence: lstamata@fredhutch.org amcguire@fredhutch.org mehul.s.suthar@emory.edu
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Preview PDF
Loading

SUMMARY

SARS-CoV-2 is one of three coronaviruses that have crossed the animal-to-human barrier in the past two decades. The development of a universal human coronavirus vaccine could prevent future pandemics. We characterized 198 antibodies isolated from four COVID19+ subjects and identified 14 SARS-CoV-2 neutralizing antibodies. One targeted the NTD, one recognized an epitope in S2 and twelve bound the RBD. Three anti-RBD neutralizing antibodies cross-neutralized 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 rather than the antibody epitope specificity regulates the in vivo protective potential of anti-SARS-CoV-2 antibodies. The anti-S2 antibody also neutralized SARS-CoV-1 and all four cross-neutralizing antibodies neutralized 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.

Competing Interest Statement

L.S., M.P., and A.T.M. have filed a provisional patent application on the SARS-CoV-2 specific monoclonal antibodies from CV1, CV2 and PCV1. L.S., M.P., A.T.M., and A.F. have filed a provisional patent application on the mAbs from CV3. H.C. reports grants from Bill and Melinda Gates Foundation, and NIH during the conduct of the study; consulting with Merck and the Bill & Melinda Gates Foundation, grants from Sanofi Pasteur and Gates Ventures outside the submitted work, and non-financial support from Cepheid and Ellume.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
Back to top
PreviousNext
Posted March 24, 2021.
Download PDF
Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Isolation and Characterization of Cross-Neutralizing Coronavirus Antibodies from COVID-19+ Subjects
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
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, Emily 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
bioRxiv 2021.03.23.436684; doi: https://doi.org/10.1101/2021.03.23.436684
Reddit logo Twitter logo Facebook logo LinkedIn logo Mendeley logo
Citation Tools
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, Emily 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
bioRxiv 2021.03.23.436684; doi: https://doi.org/10.1101/2021.03.23.436684

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Immunology
Subject Areas
All Articles
  • Animal Behavior and Cognition (4866)
  • Biochemistry (10821)
  • Bioengineering (8068)
  • Bioinformatics (27381)
  • Biophysics (14030)
  • Cancer Biology (11166)
  • Cell Biology (16106)
  • Clinical Trials (138)
  • Developmental Biology (8808)
  • Ecology (13332)
  • Epidemiology (2067)
  • Evolutionary Biology (17399)
  • Genetics (11705)
  • Genomics (15964)
  • Immunology (11061)
  • Microbiology (26169)
  • Molecular Biology (10680)
  • Neuroscience (56748)
  • Paleontology (422)
  • Pathology (1737)
  • Pharmacology and Toxicology (3012)
  • Physiology (4569)
  • Plant Biology (9670)
  • Scientific Communication and Education (1617)
  • Synthetic Biology (2699)
  • Systems Biology (6997)
  • Zoology (1515)