Circulating SARS-CoV-2 spike N439K variants maintain fitness while evading antibody-mediated immunity

Thomson, E. C. et al. (2021) Circulating SARS-CoV-2 spike N439K variants maintain fitness while evading antibody-mediated immunity. Cell, 184(5), 1171-1187.e20. (doi: 10.1016/j.cell.2021.01.037) (PMID:33621484) (PMCID:PMC7843029)

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SARS-CoV-2 can mutate and evade immunity, with consequences for efficacy of emerging vaccines and antibody therapeutics. Herein we demonstrate that the immunodominant SARS-CoV-2 spike (S) receptor binding motif (RBM) is a highly variable region of S, and provide epidemiological, clinical, and molecular characterization of a prevalent, sentinel RBM mutation, N439K. We demonstrate N439K S protein has enhanced binding affinity to the hACE2 receptor, and N439K viruses have similar in vitro replication fitness and cause infections with similar clinical outcomes as compared to wild-type. We show the N439K mutation confers resistance against several neutralizing monoclonal antibodies, including one authorized for emergency use by the FDA, and reduces the activity of some polyclonal sera from persons recovered from infection. Immune evasion mutations that maintain virulence and fitness such as N439K can emerge within SARS-CoV-2 S, highlighting the need for ongoing molecular surveillance to guide development and usage of vaccines and therapeutics.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Shah, Dr Rajiv and Li, Dr Kathy and Robertson, Professor David and Wickenhagen, Mr Arthur and Jarrett, Professor Ruth and Mair, Mr Daniel and Tong, Dr Lily and Davis, Dr Chris and Jesudason, Dr Natasha and Da Silva Filipe, Dr Ana and Shepherd, Dr James and Hughes, Dr Joseph and Rihn, Dr Suzannah and Nichols, Mrs Jenna and Carmichael, Dr Stephen and Vattipally, Dr Sreenu and Ho, Dr Antonia and Nomikou, Dr Kyriaki and Lytras, Spyros and Thomson, Professor Emma and Johnson, Miss Natasha and Smollett, Dr Katherine
Authors: Thomson, E. C., Rosen, L. E., Shepherd, J. G., Spreafico, R., da Silva Filipe, A., Wojcechowskyj, J. A., Davis, C., Piccoli, L., Pascall, D. J., Dillen, J., Lytras, S., Czudnochowski, N., Shah, R., Meury, M., Jesudason, N., De Marco, A., Li, K., Bassi, J., O’Toole, A., Pinto, D., Colquhoun, R. M., Culap, K., Jackson, B., Zatta, F., Rambaut, A., Jaconi, S., Sreenu, V. B., Nix, J., Zhang, I., Jarrett, R. F., Glass, W. G., Beltramello, M., Nomikou, K., Pizzuto, M., Tong, L., Cameroni, E., Croll, T. I., Johnson, N., Di Iulio, J., Wickenhagen, A., Ceschi, A., Harbison, A. M., Mair, D., Ferrari, P., Smollett, K., Sallusto, F., Carmichael, S., Garzoni, C., Nichols, J., Galli, M., Hughes, J., Riva, A., Ho, A., Schiuma, M., Semple, M. G., Openshaw, P. J.M., Fadda, E., Baillie, J. K., Chodera, J. D., Rihn, S. J., Lycett, S. J., Virgin, H. W., Telenti, A., Corti, D., Robertson, D. L., and Snell, G.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
Journal Name:Cell
ISSN (Online):1097-4172
Published Online:28 January 2021
Copyright Holders:Copyright © 2021 The Authors
First Published:First published in Cell 184(5): 1171-1187.e20
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
310665ISARIC - Coronavirus Clinical Characterisation ConsortiumAntonia HoMedical Research Council (MRC)MC_PC_19059 - 9815274III - Centre for Virus Research