Cross-neutralization of SARS-CoV-2 by a human monoclonal SARS-CoV antibody
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Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a newly emerged coronavirus that is responsible for the current pandemic of coronavirus disease 2019 (COVID-19), which has resulted in more than 3.7 million infections and 260,000 deaths as of 6 May 2020 1,2. Vaccine and therapeutic discovery efforts are paramount to curb the pandemic spread of this zoonotic virus. The SARS-CoV-2 spike (S) glycoprotein promotes entry into host cells and is the main target of neutralizing antibodies. Here we describe several monoclonal antibodies that target the S glycoprotein of SARS-CoV-2, which we identified from memory B cells of an individual who was infected with severe acute respiratory syndrome coronavirus (SARS-CoV) in 2003. One antibody (named S309) potently neutralizes SARS-CoV-2 and SARS-CoV pseudoviruses as well as authentic SARS-CoV-2, by engaging the receptor-binding domain of the S glycoprotein. Using cryo-electron microscopy and binding assays, we show that S309 recognizes an epitope containing a glycan that is conserved within the Sarbecovirus subgenus, without competing with receptor attachment. Antibody cocktails that include S309 in combination with other antibodies that we identified further enhanced SARS-CoV-2 neutralization, and may limit the emergence of neutralization-escape mutants. These results pave the way for using S309 and antibody cocktails containing S309 for prophylaxis in individuals at a high risk of exposure or as a post-exposure therapy to limit or treat severe disease.
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Several studies have shown that authentic virus and pseudovirus neutralization correlate quite well.
“Several studies have now shown that authentic virus and pseudovirus neutralization correlate quite well (16, 86, 87).”
From mRNA vaccination boosts cross-variant neutralizing antibodies elicited by SARS-CoV-2 infection (2021) · cites this paper as [86]
Serum neutralising activity is a correlate of protection for other respiratory viruses, including influenza and respiratory syncytial virus.
“Serum neutralising activity is a correlate of protection for other respiratory viruses, including influenza35 and respiratory syncytial virus where prohylaxis with monoclonal antibodies has been used in at-risk groups36,37.”
From Sensitivity of SARS-CoV-2 B.1.1.7 to mRNA vaccine-elicited antibodies (2021) · cites this paper as [35]
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Self-citationImprinted antibody responses against SARS-CoV-2 Omicron sublineages
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A Potent and Protective Human Neutralizing Antibody Against SARS-CoV-2 Variants
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Self-citation
- Authors
- Pinto, D., Park, Y.-J., Beltramello, M., Walls, A. C., Tortorici, M. A., Bianchi, S., Jaconi, S., Culap, K., Zatta, F., De Marco, A., Peter, A., Guarino, B., Spreafico, R., Cameroni, E., Case, J. B., Chen, R. E., Havenar-Daughton, C., Snell, G., Telenti, A., Virgin, H. W., Lanzavecchia, A., Diamond, M. S., Fink, K., Veesler, D., & Corti, D.
- Affiliations
- Vir Biotechnology (Switzerland) (CH)
- University of Washington (US)
- Centre National de la Recherche Scientifique (FR)
- VIR Biotechnology (United States) (US)
- Washington University in St. Louis (US)
- Corresponding author
- Veesler, David
- Corti, Davide
- ORCID
- Pinto, Dora
- Park, Young-Jun
- Beltramello, Martina
- Walls, Alexandra C.
- Tortorici, M. Alejandra
- Bianchi, Siro
- Jaconi, Stefano
- Culap, Katja
- Zatta, Fabrizia
- Peter, Alessia
- Guarino, Barbara
- Spreafico, Roberto
- Cameroni, Elisabetta
- Case, James Brett
- Chen, Rita E.
- Havenar-Daughton, Colin
- Snell, Gyorgy
- Telenti, Amalio
- Virgin, Herbert W.
- Lanzavecchia, Antonio
- Diamond, Michael S.
- Fink, Katja
- Veesler, David
- Corti, Davide
- Venue
- Nature
- Published
- 2020-05-18
- Volume
- 583
- Issue
- 7815
- Pages
- 290-295
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W3025744748
- Cited by
- 1,885
- References
- 87
- Citations by year
- 2026: 68 · 2025: 128 · 2024: 181 · 2023: 229 · 2022: 417 · 2021: 567 · 2020: 293
- FWCI
- 49.43
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Nature (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- U.S. Department of Energy (-AC02-05CH11231, Contract No. DE-AC02-05-CH11231, 05CH11231, No. DE-AC02-05-CH11231, DE AC02 05CH11231, DE-AC02-)
- Burroughs Wellcome Fund (DE-AC02-05CH11231)
- University of Washington
- National Institutes of Health (1s10od023476-01)
- Office of Science (No. DE-AC02- 05-CH11231, DEAC02–05CH11231, AC02-05CH11231, DE-AC02, Contract No. DE-AC02-05CH11231)
- National Institute of General Medical Sciences (DE-AC02-05CH11231, R01GM120553)
- National Institute of Allergy and Infectious Diseases (HHSN272201700059C, 75N93019C00062)
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
- Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Virus Infections Studies
- Keywords
- SARS-CoV-2, COVID-19 pandemic, monoclonal antibodies, spike protein, receptor binding domain, cross-neutralization, SARS-CoV, memory B cells, antibody cocktail, neutralization escape mutants, post-exposure prophylaxis, therapeutic antibodies, carbohydrate epitopes
- MeSH terms
- Betacoronavirus, Angiotensin-Converting Enzyme 2, COVID-19, SARS-CoV-2, Animals, Antibodies, Monoclonal, Antibodies, Viral, Antibody-Dependent Cell Cytotoxicity, B-Lymphocytes, Chlorocebus aethiops, Cross Reactions, Humans, Immunoglobulin Fab Fragments, Immunologic Memory, Killer Cells, Natural, Peptidyl-Dipeptidase A, Models, Molecular, Neutralization Tests, Pneumonia, Viral, Vero Cells, Coronavirus Infections, Epitopes, B-Lymphocyte, Cryoelectron Microscopy, Severe Acute Respiratory Syndrome, Severe acute respiratory syndrome-related coronavirus, Immune Evasion, Antibodies, Neutralizing, HEK293 Cells, Pandemics, Spike Glycoprotein, Coronavirus
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