Academic Journal
Circulating SARS-CoV-2 spike N439K variants maintain fitness while evading antibody-mediated immunity
| Τίτλος: | Circulating SARS-CoV-2 spike N439K variants maintain fitness while evading antibody-mediated immunity |
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| Συγγραφείς: | Thomson, EC, Rosen, LE, Shepherd, JG, Spreafico, R, da Silva Filipe, A, Wojcechowskyj, JA, Davis, C, Piccoli, L, Pascall, DJ, 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, RM, Culap, K, Jackson, B, Zatta, F, Rambaut, A, Jaconi, S, Sreenu, VB, Nix, J, Zhang, I, Jarrett, RF, Glass, WG, Beltramello, M, Nomikou, K, Pizzuto, M, Tong, L, Cameroni, E, Croll, TI, Johnson, N, Iulio, JD, Wickenhagen, A, Ceschi, A, Harbison, AM, 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, MG, Openshaw, PJM, Fadda, E, Kenneth Baillie, J, Chodera, JD, Rihn, SJ, Lycett, SJ, Virgin, HW, Telenti, A, Corti, D, Robertson, DL, Snell, G, Connor, TR, Loman, NJ, Robson, SC, Golubchik, T, Estee Torok, M, Hamilton, WL, Bonsall, D, Awan, AR, Corden, S, Goodfellow, I, Smith, DL, Curran, MD, Parmar, S, Parker, MD, Moore, C, Fairley, DJ, Loose, MW, Watkins, J, Bull, M, Nicholls, S, Aanensen, DM, Glaysher, S, Bashton, M, Pacchiarini, N, Underwood, AP, de Silva, TI, Wang, D, Andersson, M, Chauhan, AJ, de Cesare, M, Ludden, C, Mahungu, TW, Dewar, R |
| Πηγή: | urn:ISSN:0092-8674 ; urn:ISSN:1097-4172 ; Cell, 184, 5, 1171-1187.e20 |
| Στοιχεία εκδότη: | Elsevier |
| Έτος έκδοσης: | 2021 |
| Συλλογή: | UNSW Sydney (The University of New South Wales): UNSWorks |
| Θεματικοί όροι: | 3207 Medical Microbiology, 32 Biomedical and Clinical Sciences, 31 Biological Sciences, 3204 Immunology, Prevention, Emerging Infectious Diseases, Infectious Diseases, Vaccine Related, Coronaviruses, Coronaviruses Therapeutics and Interventions, Immunization, Biodefense, Biotechnology, Coronaviruses Vaccines, 5.1 Pharmaceuticals, 2.1 Biological and endogenous factors, Infection, 3 Good Health and Well Being, Angiotensin-Converting Enzyme 2, Antibodies, Neutralizing, Viral, COVID-19, Genetic Fitness, Humans, Immune Evasion, Mutation, Phylogeny, SARS-CoV-2, Spike Glycoprotein |
| Περιγραφή: | SARS-CoV-2 can mutate and evade immunity, with consequences for efficacy of emerging vaccines and antibody therapeutics. Here, 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 US Food and Drug Administration (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. Epidemiological, clinical, molecular, and structural characterization of the N439K mutation in the SARS-CoV-2 spike receptor binding motif demonstrates that it results in similar viral fitness compared to wild-type while conferring resistance against some neutralizing monoclonal antibodies and reducing the activity of some polyclonal antibody responses. |
| Τύπος εγγράφου: | article in journal/newspaper |
| Περιγραφή αρχείου: | application/pdf |
| Γλώσσα: | unknown |
| Relation: | https://hdl.handle.net/1959.4/unsworks_74684; https://doi.org/10.1016/j.cell.2021.01.037 |
| DOI: | 10.1016/j.cell.2021.01.037 |
| Διαθεσιμότητα: | https://hdl.handle.net/1959.4/unsworks_74684 https://unsworks.unsw.edu.au/bitstreams/d56ff09e-cdc0-4986-a671-bed2af8828ed/download https://doi.org/10.1016/j.cell.2021.01.037 |
| Rights: | open access ; https://purl.org/coar/access_right/c_abf2 ; CC BY ; https://creativecommons.org/licenses/by/4.0/ ; free_to_read |
| Αριθμός Καταχώρησης: | edsbas.30F316F8 |
| Βάση Δεδομένων: | BASE |
| DOI: | 10.1016/j.cell.2021.01.037 |
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