The circulating SARS-CoV-2 spike variant N439K maintains fitness while evading antibody-mediated immunity



Thomson, Emma ORCID: 0000-0003-1482-0889, Rosen, Laura, Shepherd, James ORCID: 0000-0003-3915-048X, Spreafico, Roberto, da Silva Filipe, Ana, Wojcechowskyj, Jason, Davis, Chris, Piccoli, Luca, Pascall, David, Dillen, Josh
et al (show 50 more authors) (2020) The circulating SARS-CoV-2 spike variant N439K maintains fitness while evading antibody-mediated immunity.

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Abstract

SARS-CoV-2 can mutate to evade immunity, with consequences for the efficacy of emerging vaccines and antibody therapeutics. Herein we demonstrate that the immunodominant SARS-CoV-2 spike (S) receptor binding motif (RBM) is the most divergent region of S, and provide epidemiological, clinical, and molecular characterization of a prevalent RBM variant, N439K. We demonstrate that N439K S protein has enhanced binding affinity to the hACE2 receptor, and that N439K virus has similar clinical outcomes and in vitro replication fitness as compared to wild- type. We observed that the N439K mutation resulted in immune escape from a panel of neutralizing monoclonal antibodies, including one in clinical trials, as well as from polyclonal sera from a sizeable fraction of 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: Article
Uncontrolled Keywords: The ISARIC4C Investigators, the COVID-19 Genomics UK (COG-UK) consortium
Depositing User: Symplectic Admin
Date Deposited: 11 Jan 2021 11:20
Last Modified: 26 Aug 2021 15:10
DOI: 10.1101/2020.11.04.355842
Open Access URL: https://doi.org/10.1101/2020.11.04.355842
URI: https://livrepository.liverpool.ac.uk/id/eprint/3112390