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

2021; Cell Press; Volume: 184; Issue: 5 Linguagem: Inglês

10.1016/j.cell.2021.01.037

1097-4172

Emma C. Thomson, Laura E. Rosen, James G. Shepherd, Roberto Spreafico, Ana da Silva Filipe, Jason A. Wojcechowskyj, Christopher Davis, Luca Piccoli, David J. Pascall, Josh R. Dillen, Spyros Lytras, Nadine Czudnochowski, Rajiv Shah, Marcel Meury, Natasha Jesudason, Anna De Marco, Kathy Li, Jessica Bassi, Áine O’Toole, Dora Pinto, Rachel Colquhoun, Katja Culap, Ben Jackson, Fabrizia Zatta, Andrew Rambaut, Stefano Jaconi, Vattipally B. Sreenu, Jay C. Nix, Ivy Zhang, Ruth F. Jarrett, William G. Glass, Martina Beltramello, Kyriaki Nomikou, Matteo Samuele Pizzuto, L. Tong, Elisabetta Cameroni, Tristan I. Croll, Natasha Johnson, Julia di Iulio, Arthur Wickenhagen, Alessandro Ceschi, Aoife M. Harbison, Daniel Mair, Paolo Ferrari, Katherine Smollett, Federica Sallusto, Stephen Carmichael, Christian Garzoni, Jenna Nichols, Massimo Galli, Joseph Hughes, Agostino Riva, Antonia Ho, Marco Schiuma, Malcolm G. Semple, Peter Openshaw, Elisa Fadda, J. Kenneth Baillie, John D. Chodera, Suzannah J. Rihn, Samantha Lycett, Herbert W. Virgin, Amalio Telenti, Davide Corti, David L. Robertson, Gyorgy Snell,

Monoclonal and Polyclonal Antibodies Research

Summary 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.