The circulating SARS-CoV-2 spike variant N439K maintains fitness while evading antibody-mediated immunity
Emma C Thomson; Laura E Rosen; James G Shepherd; Roberto Spreafico; Ana da Silva Filipe; Jason A Wojcechowskyj; Chris Davis; Luca Piccoli; David J Pascall; Josh Dillen; Spyros Lytras; Nadine Czudnochowski; Rajiv Shah; Marcel Meury; Natasha Jesudason; Anna De Marco; Kathy Li; Jessica Bassi; Dora Pinto; Rachel M Colquhoun; Katja Culap; Ben Jackson; Fabrizia Zatta; Andrew Rambaut; Stefano Jaconi; Vattipally B Sreenu; Jay Nix; Ruth F Jarrett; Martina Beltramello; Kyriaki Nomikou; Matteo Pizzuto; Lily Tong; Elisabetta Cameroni; Natasha Johnson; Arthur Wickenhagen; Alessandro Ceschi; Daniel Mair; Paolo Ferrari; Katherine Smollett; Federica Sallusto; Stephen Carmichael; Christian Garzoni; Jenna Nichols; Massimo Galli; Joseph Hughes; Agostino Riva; Antonia Ho; Peter JM Openshaw; Kenneth Baillie; - The ISARIC4C Investigators; - COVID-19 Genomics UK (COG-UK) consortium; Suzannah J Rihn; Samantha J Lycett; Herbert W Virgin; Amalio Telenti; Davide Corti; David L Robertson; Gyorgy Snell.
Preprint
en Inglés
| PREPRINT-BIORXIV | ID: ppbiorxiv-355842
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.
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