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.

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