Structural and functional ramifications of antigenic drift in recent SARS-CoV-2 variants

Meng Yuan, Deli Huang, Chang-Chun D. Lee, Nicholas C. Wu, Abigail M. Jackson, Xueyong Zhu, Hejun Liu, Linghang Peng, Marit J. van Gils, Rogier W. Sanders, Dennis R. Burton, S. Momsen Reincke, Harald Prüss, Jakob Kreye, David Nemazee, Andrew B. Ward, Ian A. Wilson

Research output: Working paper

Abstract

The protective efficacy of neutralizing antibodies (nAbs) elicited during natural infection with SARS-CoV-2 and by vaccination based on its spike protein has been compromised with emergence of the recent SARS-CoV-2 variants. Residues E484 and K417 in the receptor-binding site (RBS) are both mutated in lineages first described in South Africa (B.1.351) and Brazil (B.1.1.28.1). The nAbs isolated from SARS-CoV-2 patients are preferentially encoded by certain heavy-chain germline genes and the two most frequently elicited antibody families (IGHV3-53/3-66 and IGHV1-2) can each bind the RBS in two different binding modes. However, their binding and neutralization are abrogated by either the E484K or K417N mutation, whereas nAbs to the cross-reactive CR3022 and S309 sites are largely unaffected. This structural and functional analysis illustrates why mutations at E484 and K417 adversely affect major classes of nAbs to SARS-CoV-2 with consequences for next-generation COVID-19 vaccines.Competing Interest StatementRelated to this work, the German Center for Neurodegenerative Diseases (DZNE) and Charite - Universitatsmedizin Berlin have filed a patent application that included the anti-SARS-CoV-2 antibody CV05-163.
Original languageEnglish (US)
PublisherCold Spring Harbor Laboratory Press
Number of pages50
DOIs
StateIn preparation - Feb 17 2021

Publication series

NamebioRxiv
PublisherCold Spring Harbor Laboratory Press

Keywords

  • Coronavirus
  • COVID-19
  • severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
  • Novel coronavirus
  • 2019-nCoV
  • Pandemic

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