Ultrapotent human antibodies protect against SARS-CoV-2 challenge via multiple mechanisms
Open accessAbstract
A strong cocktail against SARS-CoV-2: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is initiated by the trimeric spike protein that decorates the virus and binds the ACE2 receptor. Antibodies against the spike that neutralize viral infection have potential as therapeutics. Tortorici et al. describe two very potent antibodies, S2E12 and S2M11. Electron microscopy structures characterized the binding and showed that S2E12 traps the spike in a conformation that cannot bind ACE2. Both antibodies protected hamsters against SARS-CoV-2 challenge and may be useful in antibody cocktails to combat the virus and prevent the development of resistance. Science , this issue p. 950
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Other groups have reported comparable findings with vaccinee and convalescent plasma across various pseudotype and authentic virus assays.
“In addition, similar results have been reported by others using vaccinee and convalescent plasmas and a variety of different pseudotype and authentic virus assays15,31,45–49.”
From mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants (2021) · cites this paper as [31]
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 [36]
Residue S477 is near the receptor binding site and forms part of the epitope recognized by the S2E12 and C102 neutralizing antibodies.
“Residue S477 is close to the receptor binding site (Fig ED2) and part of the epitope recognized by the S2E12 and C102 neutralizing antibodies 17,18 .”
From Spread of a SARS-CoV-2 variant through Europe in the summer of 2020 (2021) · cites this paper as [18]
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A serum-stable RNA aptamer specific for SARS-CoV-2 neutralizes viral entry
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Isolation and characterization of cross-neutralizing coronavirus antibodies from COVID-19+ subjects
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- Authors
- Tortorici, M. A., Beltramello, M., Lempp, F. A., Pinto, D., Dang, H. V., Rosen, L. E., McCallum, M., Bowen, J., Minola, A., Jaconi, S., Zatta, F., De Marco, A., Guarino, B., Bianchi, S., Lauron, E. J., Tucker, H., Zhou, J., Peter, A., Havenar-Daughton, C., Wojcechowskyj, J. A., Case, J. B., Chen, R. E., Kaiser, H., Montiel-Ruiz, M., Meury, M., Czudnochowski, N., Spreafico, R., Dillen, J., Ng, C., Sprugasci, N., Culap, K., Benigni, F., Abdelnabi, R., Foo, S.-Y. C., Schmid, M. A., Cameroni, E., Riva, A., Gabrieli, A., Galli, M., Pizzuto, M. S., Neyts, J., Diamond, M. S., Virgin, H. W., Snell, G., Corti, D., Fink, K., & Veesler, D.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Vir Biotechnology (Switzerland) (CH)
- VIR Biotechnology (United States) (US)
- University of Washington (US)
- Humabs BioMed SA, a subsidiary of Vir Biotechnology, Bellinzona, Switzerland.
- Vir Biotechnology, San Francisco, CA 94158, USA.
- Washington University in St. Louis (US)
- Rega Institute for Medical Research (BE)
- Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, KU Leuven, Belgium.
- University of Milan (IT)
- Corresponding author
- Tortorici, M. Alejandra
- Beltramello, Martina
- Fink, Katja
- Veesler, David
- ORCID
- Tortorici, M. Alejandra
- Beltramello, Martina
- Lempp, Florian A.
- Pinto, Dora
- Dang, Ha V.
- Rosen, Laura E.
- McCallum, Matthew
- Bowen, John
- Jaconi, Stefano
- Zatta, Fabrizia
- De Marco, Anna
- Guarino, Barbara
- Bianchi, Siro
- Lauron, Elvin J.
- Tucker, Heather
- Zhou, Jiayi
- Peter, Alessia
- Havenar-Daughton, Colin
- Wojcechowskyj, Jason A.
- Case, James Brett
- Chen, Rita E.
- Kaiser, Hannah
- Montiel-Ruiz, Martin
- Meury, Marcel
- Czudnochowski, Nadine
- Spreafico, Roberto
- Dillen, Josh
- Ng, Cindy
- Sprugasci, Nicole
- Culap, Katja
- Benigni, Fabio
- Abdelnabi, Rana
- Foo, Shi-Yan Caroline
- Schmid, Michael A.
- Cameroni, Elisabetta
- Riva, Agostino
- Gabrieli, Arianna
- Galli, Massimo
- Pizzuto, Matteo S.
- Neyts, Johan
- Diamond, Michael S.
- Virgin, Herbert W.
- Snell, Gyorgy
- Corti, Davide
- Fink, Katja
- Veesler, David
- Venue
- Science
- Published
- 2020-11-20
- Volume
- 370
- Issue
- 6519
- Pages
- 950-957
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC7857395
- OpenAlex
- W3089112814
- Cited by
- 510
- References
- 83
- Citations by year
- 2026: 12 · 2025: 23 · 2024: 45 · 2023: 63 · 2022: 142 · 2021: 204 · 2020: 20
- FWCI
- 14.11
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Science (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DORA PSI (Paul Scherrer Institute) (submittedVersion, cc-by)
- Lirias (KU Leuven) (submittedVersion, cc-by)
- Archivio Istituzionale della Ricerca (Universita Degli Studi Di Milano) (submittedVersion, other-oa)
- Funders
- National Institute of General Medical Sciences (GM120553)
- 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 › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
- Keywords
- SARS-CoV-2, neutralizing antibodies, ACE2 receptor, spike protein, receptor binding domain, antibody cocktail, viral escape mutants
- MeSH terms
- Protein Domains, Betacoronavirus, Angiotensin-Converting Enzyme 2, COVID-19, SARS-CoV-2, Animals, Antibodies, Viral, Cricetulus, Cricetinae, Humans, Peptidyl-Dipeptidase A, Microscopy, Electron, Pneumonia, Viral, Immunodominant Epitopes, CHO Cells, Coronavirus Infections, Cryoelectron Microscopy, Amino Acid Motifs, Antibodies, Neutralizing, HEK293 Cells, Pandemics, Spike Glycoprotein, Coronavirus
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