Circulating SARS-CoV-2 spike N439K variants maintain fitness while evading antibody-mediated immunity
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 molecu...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Elsevier
2021
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| _version_ | 1797100770738307072 |
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| author | 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 Di Iulio, J Wickenhagen, A Ceschi, A Harbison, AM Mair, D Ferrari, P Smollett, K Sallusto, F Carmichael, S Garzoni, C Nichols, J Galli, M Lee, J Merson, L Et al. |
| author_facet | 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 Di Iulio, J Wickenhagen, A Ceschi, A Harbison, AM Mair, D Ferrari, P Smollett, K Sallusto, F Carmichael, S Garzoni, C Nichols, J Galli, M Lee, J Merson, L Et al. |
| author_sort | Thomson, EC |
| collection | OXFORD |
| description | 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.
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| first_indexed | 2024-03-07T05:42:20Z |
| format | Journal article |
| id | oxford-uuid:e5ffe30a-5198-4c72-b6e9-b138c7f85548 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T05:42:20Z |
| publishDate | 2021 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | oxford-uuid:e5ffe30a-5198-4c72-b6e9-b138c7f855482022-03-27T10:28:23ZCirculating SARS-CoV-2 spike N439K variants maintain fitness while evading antibody-mediated immunityJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:e5ffe30a-5198-4c72-b6e9-b138c7f85548EnglishSymplectic ElementsElsevier2021Thomson, ECRosen, LEShepherd, JGSpreafico, Rda Silva Filipe, AWojcechowskyj, JADavis, CPiccoli, LPascall, DJDillen, JLytras, SCzudnochowski, NShah, RMeury, MJesudason, NDe Marco, ALi, KBassi, JO’Toole, APinto, DColquhoun, RMCulap, KJackson, BZatta, FRambaut, AJaconi, SSreenu, VBNix, JZhang, IJarrett, RFGlass, WGBeltramello, MNomikou, KPizzuto, MTong, LCameroni, ECroll, TIJohnson, NDi Iulio, JWickenhagen, ACeschi, AHarbison, AMMair, DFerrari, PSmollett, KSallusto, FCarmichael, SGarzoni, CNichols, JGalli, MLee, JMerson, LEt al.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. |
| spellingShingle | 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 Di Iulio, J Wickenhagen, A Ceschi, A Harbison, AM Mair, D Ferrari, P Smollett, K Sallusto, F Carmichael, S Garzoni, C Nichols, J Galli, M Lee, J Merson, L Et al. Circulating SARS-CoV-2 spike N439K variants maintain fitness while evading antibody-mediated immunity |
| title | Circulating SARS-CoV-2 spike N439K variants maintain fitness while evading antibody-mediated immunity |
| title_full | Circulating SARS-CoV-2 spike N439K variants maintain fitness while evading antibody-mediated immunity |
| title_fullStr | Circulating SARS-CoV-2 spike N439K variants maintain fitness while evading antibody-mediated immunity |
| title_full_unstemmed | Circulating SARS-CoV-2 spike N439K variants maintain fitness while evading antibody-mediated immunity |
| title_short | Circulating SARS-CoV-2 spike N439K variants maintain fitness while evading antibody-mediated immunity |
| title_sort | circulating sars cov 2 spike n439k variants maintain fitness while evading antibody mediated immunity |
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