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Genetic and structural basis for SARS-CoV-2 variant neutralization by a two-antibody cocktail
Open accessAbstract
Understanding the molecular basis for immune recognition of SARS-CoV-2 spike glycoprotein antigenic sites will inform the development of improved therapeutics. We determined the structures of two human monoclonal antibodies-AZD8895 and AZD1061-which form the basis of the investigational antibody cocktail AZD7442, in complex with the receptor-binding domain (RBD) of SARS-CoV-2 to define the genetic and structural basis of neutralization. AZD8895 forms an 'aromatic cage' at the heavy/light chain interface using germ line-encoded residues in complementarity-determining regions (CDRs) 2 and 3 of the heavy chain and CDRs 1 and 3 of the light chain. These structural features explain why highly similar antibodies (public clonotypes) have been isolated from multiple individuals. AZD1061 has an unusually long LCDR1; the HCDR3 makes interactions with the opposite face of the RBD from that of AZD8895. Using deep mutational scanning and neutralization escape selection experiments, we comprehensively mapped the crucial binding residues of both antibodies and identified positions of concern with regards to virus escape from antibody-mediated neutralization. Both AZD8895 and AZD1061 have strong neutralizing activity against SARS-CoV-2 and variants of concern with antigenic substitutions in the RBD. We conclude that germ line-encoded antibody features enable recognition of the SARS-CoV-2 spike RBD and demonstrate the utility of the cocktail AZD7442 in neutralizing emerging variant viruses.
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“Importantly, our spike did not contain R346K, which has been observed at relatively low frequency (<10%) within the Omicron lineage, but which is known to mediate escape from class 3 neutralizing monoclonal antibodies such as AZD1061/cilgavimab (Barnes et al., 2020; Dong et al., 2021; Greaney et al., 2021b).”
From mRNA-based COVID-19 vaccine boosters induce neutralizing immunity against SARS-CoV-2 Omicron variant (2022) · cites this paper as Dong et al., 2021
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Coot : model-building tools for molecular graphics
Emsley, P., & Cowtan, K. (2004) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444904019158 · Cited by 30,571
A novel coronavirus from patients with pneumonia in China, 2019
Zhu, N., Zhang, D., Wang, W., Li, X., Yang, B., Song, J., Zhao, X., Huang, B., Shi, W., Lu, R., et al. (2020) · New England Journal of Medicine · doi:10.1056/nejmoa2001017 · Cited by 28,244
PHENIX : a comprehensive Python-based system for macromolecular structure solution
Adams, P. D., Afonine, P. V., Bunkóczi, G., Chen, V. B., Davis, I. W., Echols, N., Headd, J. J., Hung, L.-W., Kapral, G. J., Grosse-Kunstleve, R. W., et al. (2010) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444909052925 · Cited by 23,716
A pneumonia outbreak associated with a new coronavirus of probable bat origin
Zhou, P., Yang, X.-L., Wang, X.-G., Hu, B., Zhang, L., Zhang, W., Si, H.-R., Zhu, Y., Li, B., Huang, C.-L., et al. (2020) · Nature · doi:10.1038/s41586-020-2012-7 · Cited by 21,969
Phaser crystallographic software
McCoy, A. J., Grosse-Kunstleve, R. W., Adams, P. D., Winn, M. D., Storoni, L. C., & Read, R. J. (2007) · Journal of Applied Crystallography · doi:10.1107/s0021889807021206 · Cited by 20,612
Hoffmann, M., Kleine-Weber, H., Schroeder, S., Krüger, N., Herrler, T., Erichsen, S., Schiergens, T. S., Herrler, G., Wu, N.-H., Nitsche, A., et al. (2020) · Cell · doi:10.1016/j.cell.2020.02.052 · Cited by 20,286
Kabsch, W. (2010) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444909047337 · Cited by 16,463
Fast, scalable generation of high-quality protein multiple sequence alignments using Clustal Omega
Sievers, F., Wilm, A., Dineen, D., Gibson, T., Karplus, K., Li, W.-Z., Lopez, R., McWilliam, H., Remmert, M., Söding, J., et al. (2011) · Molecular Systems Biology · doi:10.1038/msb.2011.75 · Cited by 15,576
WebLogo: A Sequence Logo Generator: Figure 1Preprint
Crooks, G. E., Hon, G. C., Chandonia, J., & Brenner, S. E. (2004) · Genome Research · doi:10.1101/gr.849004 · Cited by 12,480
Overview of the CCP 4 suite and current developments
Winn, M. D., Ballard, C. C., Cowtan, K. D., Dodson, E. J., Emsley, P., Evans, P. R., Keegan, R. M., Krissinel, E. B., Leslie, A. G. W., McCoy, A., et al. (2011) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444910045749 · Cited by 12,353
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Omicron escapes the majority of existing SARS-CoV-2 neutralizing antibodies
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Self-citationBroadly neutralizing antibodies overcome SARS-CoV-2 Omicron antigenic shift
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Self-citationmRNA-based COVID-19 vaccine boosters induce neutralizing immunity against SARS-CoV-2 Omicron variant
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“Importantly, our spike did not contain R346K, which has been observed at relatively low frequency (<10%) within the Omicron lineage, but which is known to mediate escape from class 3 neutralizing monoclonal antibodies such as AZD1061/cilgavimab (Barnes et al., 2020; Dong et al., 2021; Greaney et al., 2021b).”
Intramuscular AZD7442 (Tixagevimab–Cilgavimab) for Prevention of Covid-19
Levin, M. J., Ustianowski, A., Wit, S. D., Launay, O., Avila, M., Templeton, A., Yuan, Y., Seegobin, S., Ellery, A., Levinson, D. J., et al. (2022) · New England Journal of Medicine · doi:10.1056/nejmoa2116620 · Cited by 694
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Metadata
- Authors
- Dong, J., Zost, S. J., Greaney, A. J., Starr, T. N., Dingens, A. S., Chen, E. C., Chen, R. E., Case, J. B., Sutton, R. E., Gilchuk, P., Rodriguez, J., Armstrong, E., Gainza, C., Nargi, R. S., Binshtein, E., Xie, X., Zhang, X., Shi, P.-Y., Logue, J., Weston, S., McGrath, M. E., Frieman, M. B., Brady, T., Tuffy, K. M., Bright, H., Loo, Y.-M., McTamney, P. M., Esser, M. T., Carnahan, R. H., Diamond, M. S., Bloom, J. D., & Crowe, J. E.
- Affiliations
- Vanderbilt University Medical Center (US)
- University of Washington (US)
- Fred Hutch Cancer Center (US)
- Washington University in St. Louis (US)
- The University of Texas Medical Branch at Galveston (US)
- University of Maryland, College Park (US)
- AstraZeneca (United States) (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Crowe, James E.
- ORCID
- Dong, Jinhui
- Zost, Seth J.
- Greaney, Allison J.
- Starr, Tyler N.
- Dingens, Adam S.
- Chen, Elaine C.
- Chen, Rita E.
- Case, James Brett
- Gilchuk, Pavlo
- Rodriguez, Jessica
- Binshtein, Elad
- Xie, Xuping
- Zhang, Xianwen
- Shi, Pei-Yong
- Logue, James
- Weston, Stuart
- McGrath, Marisa E.
- Frieman, Matthew B.
- Brady, Tyler
- Tuffy, Kevin M.
- Bright, Helen
- Loo, Yueh-Ming
- Esser, Mark T.
- Carnahan, Robert H.
- Diamond, Michael S.
- Bloom, Jesse D.
- Crowe, James E.
- Venue
- Nature Microbiology
- Published
- 2021-09-21
- Volume
- 6
- Issue
- 10
- Pages
- 1233-1244
- ISSN
- 2058-5276 (ISSN-L)
- PMC
- PMC8543371
- OpenAlex
- W3199394546
- Cited by
- 285
- References
- 84
- Citations by year
- 2026: 12 · 2025: 17 · 2024: 43 · 2023: 72 · 2022: 107 · 2021: 33
- FWCI
- 20.13
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Nature Microbiology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (AI095202, 75N93019C00062, AI157155, AI141707, 75N93019C00074, AI150739)
- U.S. Department of Health & Human Services | NIH | National Center for Advancing Translational Sciences (UL1TR001439)
- United States Department of Defense | Defense Advanced Research Projects Agency (HR0011-18-3-0001, HR0011-18-2-0001)
- Merck KGaA (Future Insight Prize 2019)
- DOE | LDRD | Argonne National Laboratory (DE-AC02-06CH11357)
- Michigan Economic Development Corporation (085P1000817)
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
- Life Sciences › Immunology and Microbiology › Immunology › Monoclonal and Polyclonal Antibodies Research
- Keywords
- SARS-CoV-2, spike protein, receptor binding domain, monoclonal antibodies, antibody neutralization, antibody-antigen complex structure, hypervariable region, HCDR3, neutralization escape, variants of concern, deep mutational scanning
- MeSH terms
- Protein Domains, COVID-19, SARS-CoV-2, Antibodies, Monoclonal, Antibodies, Viral, Antigenic Variation, Binding Sites, Humans, Mutation, Complementarity Determining Regions, Antibodies, Neutralizing, Spike Glycoprotein, Coronavirus
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