1. Circulating SARS-CoV-2 spike N439K variants maintain fitness while evading antibody-mediated immunity
- Author
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Thomson, Emma C, Rosen, Laura E, Shepherd, James G, Spreafico, Roberto, da Silva Filipe, Ana, Wojcechowskyj, Jason A, Davis, Chris, Piccoli, Luca, Pascall, David J, Dillen, Josh, Lytras, Spyros, Czudnochowski, Nadine, Shah, Rajiv, Meury, Marcel, Jesudason, Natasha, De Marco, Anna, Li, Kathy, Bassi, Jessica, O’Toole, Aine, Pinto, Dora, Colquhoun, Rachel M, Culap, Katja, Jackson, Ben, Zatta, Fabrizia, Rambaut, Andrew, Jaconi, Stefano, Sreenu, Vattipally B, Nix, Jay, Zhang, Ivy, Jarrett, Ruth F, Glass, William G, Beltramello, Martina, Nomikou, Kyriaki, Pizzuto, Matteo, Tong, Lily, Cameroni, Elisabetta, Croll, Tristan I, Johnson, Natasha, Di Iulio, Julia, Wickenhagen, Arthur, Ceschi, Alessandro, Harbison, Aoife M, Mair, Daniel, Ferrari, Paolo, Smollett, Katherine, Sallusto, Federica, Carmichael, Stephen, Garzoni, Christian, Nichols, Jenna, Galli, Massimo, Hughes, Joseph, Riva, Agostino, Ho, Antonia, Schiuma, Marco, Semple, Malcolm G, Openshaw, Peter JM, Fadda, Elisa, Baillie, J Kenneth, Chodera, John D, Investigators, The ISARIC4C, Consortium, the COVID-19 Genomics UK, Rihn, Suzannah J, Lycett, Samantha J, Virgin, Herbert W, Telenti, Amalio, Corti, Davide, Robertson, David L, and Snell, Gyorgy
- Subjects
Medical Microbiology ,Biomedical and Clinical Sciences ,Biological Sciences ,Immunology ,Biotechnology ,Coronaviruses Therapeutics and Interventions ,Coronaviruses ,Vaccine Related ,Infectious Diseases ,Immunization ,Emerging Infectious Diseases ,Prevention ,5.1 Pharmaceuticals ,2.1 Biological and endogenous factors ,Infection ,Good Health and Well Being ,Angiotensin-Converting Enzyme 2 ,Antibodies ,Neutralizing ,Antibodies ,Viral ,COVID-19 ,Genetic Fitness ,Humans ,Immune Evasion ,Mutation ,Phylogeny ,SARS-CoV-2 ,Spike Glycoprotein ,Coronavirus ,Virulence ,ISARIC4C Investigators ,COVID-19 Genomics UK (COG-UK) Consortium ,N439K ,Spike ,monoclonal antibody escape ,mutation ,protein structure ,receptor binding motif ,variant ,Medical and Health Sciences ,Developmental Biology ,Biological sciences ,Biomedical and clinical sciences - Abstract
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.
- Published
- 2021