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, Suzy Pickering, Rui Pedro Ribeiro Galao, Liane Dupont, Maria Lista Brotos, Jose Jimenez Guardeno, Adam Laing, Yin Wu, Magdalene Joseph, Luke Muir, Marit J van Gils, Weng Ng, Helen Duyvesteyn, Yuguang ZhaoThomas A Bowden, Manu Shankar-Hari, Annachiara Rosa, Peter Cherepanov, Laura E McCoy, Adrian Hayday, Stuart Neil, Michael Malim, Katherine Doores

Research output: Contribution to journalArticlepeer-review

34 Downloads (Pure)

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
JournalImmunity
Publication statusAccepted/In press - 29 Mar 2021

Fingerprint

Dive into the research topics of 'Neutralization potency of monoclonal antibodies recognizing dominant and subdominant epitopes on SARS-CoV-2 Spike is impacted by the B.1.1.7 variant'. Together they form a unique fingerprint.

Cite this