TY - JOUR
AU - Graham, Carl
AU - Seow, Jeffrey
AU - Huettner, Isabella
AU - Khan, Hataf
AU - Kouphou, Neophytos
AU - Acors, Sam
AU - Winstone, Helena
AU - Pickering, Suzanne
AU - Galao, Rui Pedro
AU - Dupont, Liane
AU - Lista, Maria Jose
AU - Jimenez-Guardeño, Jose M.
AU - Laing, Adam G
AU - Wu, Yin
AU - Joseph, Magdalene
AU - Muir, Luke
AU - van Gils, Marit J
AU - Ng, Weng M
AU - Duyvesteyn, Helen M E
AU - Zhao, Yuguang
AU - Bowden, Thomas A.
AU - Shankar-Hari, Manu
AU - Rosa, Annachiara
AU - Cherepanov, Peter
AU - McCoy, Laura E.
AU - Hayday, Adrian C
AU - Neil, Stuart J.D.
AU - Malim, Michael H.
AU - Doores, Katie J.
PY - 2021
DA - April
TI - Neutralization potency of monoclonal antibodies recognizing dominant and subdominant epitopes on SARS-CoV-2 Spike is impacted by the B.1.1.7 variant
JO - Immunity
EP - 1289.e6
VL - 54
IS - 6
DO - https://doi.org/10.1016/j.immuni.2021.03.023
AB - 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 &gt;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.
PB - Elsevier
UR - https://www.research.ed.ac.uk/en/publications/1674cb54-fcda-4300-a1c4-fd804b1a2d1f
KW - Coronavirus (COVID-19)
ER