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

Abstract

How the Delta variant evades defenses In the course of the COVID-19 epidemic, variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continue to emerge, some of which evade immunity or increase transmission. In late 2020, the Delta and Kappa variants were detected, and the Delta variant became globally dominant by June 2021. McCallum et al . show that vaccine-elicited serum-neutralizing activity is reduced against these variants. Based on biochemistry and structural studies, the authors show that mutations in the domain that binds the ACE2 receptor abrogate binding to some monoclonal antibodies but do not improve ACE2 binding, suggesting that they emerged to escape immune recognition. Remodeling of the N-terminal domain allows the variants to escape recognition by most neutralizing antibodies that target it. The work could guide the development of next-generation vaccines and antibody therapies. —VV

Cited by papers we hold 4

• Neutralization, effector function and immune imprinting of Omicron variants · 2023
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• Omicron spike function and neutralizing activity elicited by a comprehensive panel of vaccines · 2022
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• Conformational dynamics of the Beta and Kappa SARS-CoV-2 spike proteins and their complexes with ACE2 receptor revealed by cryo-EM · 2021
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• Membrane fusion and immune evasion by the spike protein of SARS-CoV-2 Delta variant · 2021
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