Molecular basis of immune evasion by the Delta and Kappa SARS-CoV-2 variants

Matthew McCallum; Alexandra C Walls; Kaitlin R Sprouse; John E Bowen; Laura E Rosen; Ha V Dang; Anna De Marco; Nicholas Franko; Sasha W Tilles; Jennifer Logue; Marcos C Miranda; Margaret Ahlrichs; Lauren Carter; Gyorgy Snell; Matteo Samuele Pizzuto; Helen Y Chu; Wesley C Van Voorhis; Davide Corti; David Veesler

doi:10.1126/science.abl8506

Molecular basis of immune evasion by the Delta and Kappa SARS-CoV-2 variants

Science. 2021 Dec 24;374(6575):1621-1626. doi: 10.1126/science.abl8506. Epub 2021 Nov 9.

Authors

Matthew McCallum¹, Alexandra C Walls¹, Kaitlin R Sprouse¹, John E Bowen¹, Laura E Rosen², Ha V Dang¹, Anna De Marco³, Nicholas Franko⁴, Sasha W Tilles⁵, Jennifer Logue⁴, Marcos C Miranda^{1

6}, Margaret Ahlrichs^{1

6}, Lauren Carter^{1

6}, Gyorgy Snell², Matteo Samuele Pizzuto³, Helen Y Chu⁴, Wesley C Van Voorhis⁵, Davide Corti³, David Veesler^{1

7}

Affiliations

¹ Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
² Vir Biotechnology, San Francisco, CA 94158, USA.
³ Humabs Biomed SA, a subsidiary of Vir Biotechnology, 6500 Bellinzona, Switzerland.
⁴ Division of Allergy and Infectious Diseases, University of Washington, Seattle, WA 98195, USA.
⁵ 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.
⁶ Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.
⁷ Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195, USA.

PMID: 34751595
DOI: 10.1126/science.abl8506

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.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

2019-nCoV Vaccine mRNA-1273 / immunology
Ad26COVS1 / immunology
Angiotensin-Converting Enzyme 2 / metabolism
Antibodies, Neutralizing / blood
Antibodies, Neutralizing / immunology
Antibodies, Neutralizing / metabolism
Antibodies, Viral / blood
Antibodies, Viral / immunology
Antibodies, Viral / metabolism
Antigens, Viral / chemistry
Antigens, Viral / immunology
BNT162 Vaccine / immunology
COVID-19 Vaccines / immunology*
Cryoelectron Microscopy
Humans
Immune Evasion*
Models, Molecular
Mutation
Protein Binding
Protein Conformation
Protein Domains
Protein Folding
Receptors, Coronavirus / metabolism
SARS-CoV-2 / chemistry
SARS-CoV-2 / genetics
SARS-CoV-2 / immunology*
SARS-CoV-2 / pathogenicity
Spike Glycoprotein, Coronavirus / chemistry*
Spike Glycoprotein, Coronavirus / genetics
Spike Glycoprotein, Coronavirus / immunology*
Spike Glycoprotein, Coronavirus / metabolism

Substances

Ad26COVS1
Antibodies, Neutralizing
Antibodies, Viral
Antigens, Viral
COVID-19 Vaccines
Receptors, Coronavirus
Spike Glycoprotein, Coronavirus
spike protein, SARS-CoV-2
ACE2 protein, human
Angiotensin-Converting Enzyme 2
2019-nCoV Vaccine mRNA-1273
BNT162 Vaccine

Supplementary concepts

SARS-CoV-2 variants

Abstract

Publication types

MeSH terms

Substances

Supplementary concepts

Grants and funding