Neutralization potency of monoclonal antibodies recognizing dominant and subdominant epitopes on SARS-CoV-2 Spike is impacted by the B.1.1.7 variant

Carl Graham, Jeffrey Seow, Isabella Huettner, Hataf Khan, Neophytos Kouphou, Sam Acors, Helena Winstone, Suzanne Pickering, Rui Pedro Galao, Liane Dupont, Maria Jose Lista, Jose M. Jimenez-Guardeño, Adam G. Laing, Yin Wu, Magdalene Joseph, Luke Muir, Marit J. van Gils, Weng M. Ng, Helen M.E. Duyvesteyn, Yuguang ZhaoThomas A. Bowden, Manu Shankar-Hari, Annachiara Rosa, Peter Cherepanov, Laura E. McCoy, Adrian C. Hayday, Stuart J.D. Neil, Michael H. Malim, Katie J. Doores*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

86 Citations (Scopus)

Abstract

Interaction of the SARS-CoV-2 Spike receptor binding domain (RBD) with the receptor ACE2 on host cells is essential for viral entry. RBD is the dominant target for neutralizing antibodies, and several neutralizing epitopes on RBD have been molecularly characterized. Analysis of circulating SARS-CoV-2 variants has revealed mutations arising in the RBD, N-terminal domain (NTD) and S2 subunits of Spike. To understand how these mutations affect Spike antigenicity, we isolated and characterized >100 monoclonal antibodies targeting epitopes on RBD, NTD, and S2 from SARS-CoV-2-infected individuals. Approximately 45% showed neutralizing activity, of which ∼20% were NTD specific. NTD-specific antibodies formed two distinct groups: the first was highly potent against infectious virus, whereas the second was less potent and displayed glycan-dependant neutralization activity. Mutations present in B.1.1.7 Spike frequently conferred neutralization resistance to NTD-specific antibodies. This work demonstrates that neutralizing antibodies targeting subdominant epitopes should be considered when investigating antigenic drift in emerging variants.

Original languageEnglish
Pages (from-to)1276-1289.e6
JournalImmunity
Volume54
Issue number6
DOIs
Publication statusPublished - 8 Jun 2021

Keywords

  • antibody
  • B.1.1.7
  • immune escape
  • neutralization
  • neutralizing epitope
  • SARS-CoV-2
  • variant of concern

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