@article{Graham_C-2021_83626, title = {Neutralization potency of monoclonal antibodies recognizing dominant and subdominant epitopes on SARS-CoV-2 Spike is impacted by the B.1.1.7 variant}, author = {Graham, C. and Seow, J. and Huettner, I. and Khan, H. and Kouphou, N. and Acors, S. and Winstone, H. and Pickering, S. and Galao, R. and Dupont, L. and Lista, M. and Jimenez-Guardeño, J. and Laing, A. and Wu, Y. and Joseph, M. and Muir, L. and van Gils, M. and Ng, W. and Duyvesteyn, H. and Zhao, Y. and Bowden, T. and Shankar-Hari, M. and Rosa, A. and Cherepanov, P. and McCoy, L. and Hayday, A. and Neil, S. and Malim, M. and Doores, K.}, month = {apr}, year = {2021}, 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.}, pages = {1276-1289.e6}, volume = {54}, issue = {6}, journal = {Immunity}, publisher = {Elsevier}, url = {https://doi.org/10.1016/j.immuni.2021.03.023}, }