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

Matthew McCallum(University of Washington), Alexandra C. Walls(University of Washington), Kaitlin R. Sprouse(University of Washington), John E. Bowen(University of Washington), Laura E. Rosen(VIR Biotechnology (United States)), Ha V. Dang(University of Washington), Anna De Marco(Vir Biotechnology (Switzerland)), Nicholas Franko(University of Washington), Sasha W. Tilles(University of Washington), Jennifer K. Logue(University of Washington), Marcos C. Miranda(University of Washington), Maggie Ahlrichs(University of Washington), Lauren Carter(University of Washington), Gyorgy Snell(VIR Biotechnology (United States)), Matteo Samuele Pizzuto(Vir Biotechnology (Switzerland)), Helen Y. Chu(University of Washington), Wesley C. Van Voorhis(University of Washington), Davide Corti(Vir Biotechnology (Switzerland)), David Veesler(Howard Hughes Medical Institute)
Science
December 23, 2021
Cited by 311Open Access
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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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