Broadly neutralizing antibodies target the coronavirus fusion peptide-Reference-Cited by-同舟云学术

Broadly neutralizing antibodies target the coronavirus fusion peptide

Published:2022-08-12 Issue:6607 Volume:377 Page:728-735
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Dacon Cherrelle¹^ORCID,Tucker Courtney¹²^ORCID,Peng Linghang³^ORCID,Lee Chang-Chun D.⁴^ORCID,Lin Ting-Hui⁴^ORCID,Yuan Meng⁴^ORCID,Cong Yu⁵,Wang Lingshu⁶^ORCID,Purser Lauren¹,Williams Jazmean K.⁷^ORCID,Pyo Chul-Woo⁸,Kosik Ivan⁹^ORCID,Hu Zhe⁹,Zhao Ming¹⁰^ORCID,Mohan Divya¹,Cooper Andrew J. R.¹^ORCID,Peterson Mary¹¹^ORCID,Skinner Jeff¹¹^ORCID,Dixit Saurabh⁵,Kollins Erin⁵^ORCID,Huzella Louis⁵,Perry Donna⁵,Byrum Russell⁵,Lembirik Sanae⁵^ORCID,Drawbaugh David⁵,Eaton Brett⁵^ORCID,Zhang Yi⁶^ORCID,Yang Eun Sung⁶^ORCID,Chen Man⁶^ORCID,Leung Kwanyee⁶^ORCID,Weinberg Rona S.¹²^ORCID,Pegu Amarendra⁶^ORCID,Geraghty Daniel E.⁸,Davidson Edgar⁷,Douagi Iyadh¹³^ORCID,Moir Susan¹⁴^ORCID,Yewdell Jonathan W.⁹^ORCID,Schmaljohn Connie⁵^ORCID,Crompton Peter D.¹¹^ORCID,Holbrook Michael R.⁵^ORCID,Nemazee David³^ORCID,Mascola John R.⁶,Wilson Ian A.⁴¹⁵^ORCID,Tan Joshua¹^ORCID

Affiliation:

1. Antibody Biology Unit, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA.

2. Department of Biology, The Catholic University of America, Washington, DC 20064, USA.

3. Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.

4. Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.

5. Integrated Research Facility, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD 21702, USA.

6. Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

7. Integral Molecular, Philadelphia, PA 19104, USA.

8. Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.

9. Cellular Biology Section, Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

10. Protein Chemistry Section, Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA.

11. Malaria Infection Biology and Immunity Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA.

12. New York Blood Center, Lindsley F. Kimball Research Institute, New York, NY 10065, USA.

13. Flow Cytometry Section, Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

14. B Cell Immunology Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

15. The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.

Abstract

The potential for future coronavirus outbreaks highlights the need to broadly target this group of pathogens. We used an epitope-agnostic approach to identify six monoclonal antibodies that bind to spike proteins from all seven human-infecting coronaviruses. All six antibodies target the conserved fusion peptide region adjacent to the S2′ cleavage site. COV44-62 and COV44-79 broadly neutralize alpha- and betacoronaviruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron subvariants BA.2 and BA.4/5, albeit with lower potency than receptor binding domain–specific antibodies. In crystal structures of COV44-62 and COV44-79 antigen-binding fragments with the SARS-CoV-2 fusion peptide, the fusion peptide epitope adopts a helical structure and includes the arginine residue at the S2′ cleavage site. COV44-79 limited disease caused by SARS-CoV-2 in a Syrian hamster model. These findings highlight the fusion peptide as a candidate epitope for next-generation coronavirus vaccine development.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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