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Molecular basis of immune evasion by the Delta and Kappa SARS-CoV-2 variants.
Science. 2021 Dec 24; 374(6575):1621-1626.Sci

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission leads to the emergence of variants, including the B.1.617.2 (Delta) variant of concern that is causing a new wave of infections and has become globally dominant. We show that these variants dampen the in vitro potency of vaccine-elicited serum neutralizing antibodies and provide a structural framework for describing their immune evasion. Mutations in the B.1.617.1 (Kappa) and Delta spike glycoproteins abrogate recognition by several monoclonal antibodies via alteration of key antigenic sites, including remodeling of the Delta amino-terminal domain. The angiotensin-converting enzyme 2 binding affinities of the Kappa and Delta receptor binding domains are comparable to the Wuhan-Hu-1 isolate, whereas B.1.617.2+ (Delta+) exhibits markedly reduced affinity.

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Authors+Show Affiliations

McCallum M
Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
Walls AC
Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
Sprouse KR
Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
Bowen JE
Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
Rosen LE
Vir Biotechnology, San Francisco, CA 94158, USA.
Dang HV
Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
De Marco A
Humabs Biomed SA, a subsidiary of Vir Biotechnology, 6500 Bellinzona, Switzerland.
Franko N
Division of Allergy and Infectious Diseases, University of Washington, Seattle, WA 98195, USA.
Tilles SW
Center for Emerging and Re-emerging Infectious Diseases, Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington School of Medicine, Seattle, WA 98195, USA.
Logue J
Division of Allergy and Infectious Diseases, University of Washington, Seattle, WA 98195, USA.
Miranda MC
Department of Biochemistry, University of Washington, Seattle, WA 98195, USA. Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.
Ahlrichs M
Department of Biochemistry, University of Washington, Seattle, WA 98195, USA. Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.
Carter L
Department of Biochemistry, University of Washington, Seattle, WA 98195, USA. Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.
Snell G
Vir Biotechnology, San Francisco, CA 94158, USA.
Pizzuto MS
Humabs Biomed SA, a subsidiary of Vir Biotechnology, 6500 Bellinzona, Switzerland.
Chu HY
Division of Allergy and Infectious Diseases, University of Washington, Seattle, WA 98195, USA.
Van Voorhis WC
Center for Emerging and Re-emerging Infectious Diseases, Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington School of Medicine, Seattle, WA 98195, USA.
Corti D
Humabs Biomed SA, a subsidiary of Vir Biotechnology, 6500 Bellinzona, Switzerland.
Veesler D
Department of Biochemistry, University of Washington, Seattle, WA 98195, USA. Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195, USA.

MeSH

2019-nCoV Vaccine mRNA-1273Ad26COVS1Angiotensin-Converting Enzyme 2Antibodies, NeutralizingAntibodies, ViralAntigens, ViralBNT162 VaccineCOVID-19 VaccinesCryoelectron MicroscopyHumansImmune EvasionModels, MolecularMutationProtein BindingProtein ConformationProtein DomainsProtein FoldingReceptors, CoronavirusSARS-CoV-2Spike Glycoprotein, Coronavirus

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

34751595

Citation

McCallum, Matthew, et al. "Molecular Basis of Immune Evasion By the Delta and Kappa SARS-CoV-2 Variants." Science (New York, N.Y.), vol. 374, no. 6575, 2021, pp. 1621-1626.
McCallum M, Walls AC, Sprouse KR, et al. Molecular basis of immune evasion by the Delta and Kappa SARS-CoV-2 variants. Science. 2021;374(6575):1621-1626.
McCallum, M., Walls, A. C., Sprouse, K. R., Bowen, J. E., Rosen, L. E., Dang, H. V., De Marco, A., Franko, N., Tilles, S. W., Logue, J., Miranda, M. C., Ahlrichs, M., Carter, L., Snell, G., Pizzuto, M. S., Chu, H. Y., Van Voorhis, W. C., Corti, D., & Veesler, D. (2021). Molecular basis of immune evasion by the Delta and Kappa SARS-CoV-2 variants. Science (New York, N.Y.), 374(6575), 1621-1626. https://doi.org/10.1126/science.abl8506
McCallum M, et al. Molecular Basis of Immune Evasion By the Delta and Kappa SARS-CoV-2 Variants. Science. 2021 Dec 24;374(6575):1621-1626. PubMed PMID: 34751595.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Molecular basis of immune evasion by the Delta and Kappa SARS-CoV-2 variants. AU - McCallum,Matthew, AU - Walls,Alexandra C, AU - Sprouse,Kaitlin R, AU - Bowen,John E, AU - Rosen,Laura E, AU - Dang,Ha V, AU - De Marco,Anna, AU - Franko,Nicholas, AU - Tilles,Sasha W, AU - Logue,Jennifer, AU - Miranda,Marcos C, AU - Ahlrichs,Margaret, AU - Carter,Lauren, AU - Snell,Gyorgy, AU - Pizzuto,Matteo Samuele, AU - Chu,Helen Y, AU - Van Voorhis,Wesley C, AU - Corti,Davide, AU - Veesler,David, Y1 - 2021/11/09/ PY - 2021/11/10/pubmed PY - 2022/1/15/medline PY - 2021/11/9/entrez SP - 1621 EP - 1626 JF - Science (New York, N.Y.) JO - Science VL - 374 IS - 6575 N2 - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission leads to the emergence of variants, including the B.1.617.2 (Delta) variant of concern that is causing a new wave of infections and has become globally dominant. We show that these variants dampen the in vitro potency of vaccine-elicited serum neutralizing antibodies and provide a structural framework for describing their immune evasion. Mutations in the B.1.617.1 (Kappa) and Delta spike glycoproteins abrogate recognition by several monoclonal antibodies via alteration of key antigenic sites, including remodeling of the Delta amino-terminal domain. The angiotensin-converting enzyme 2 binding affinities of the Kappa and Delta receptor binding domains are comparable to the Wuhan-Hu-1 isolate, whereas B.1.617.2+ (Delta+) exhibits markedly reduced affinity. SN - 1095-9203 UR - https://www.unboundmedicine.com/medline/citation/34751595/Molecular_basis_of_immune_evasion_by_the_Delta_and_Kappa_SARS_CoV_2_variants_ L2 - https:///www.science.org/doi/10.1126/science.abl8506?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -