1. Landscape analysis of escape variants identifies SARS-CoV-2 spike mutations that attenuate monoclonal and serum antibody neutralization
- Author
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Michael S. Diamond, Errico Jm, Ali H. Ellebedy, Haiyan Zhao, Louis Marie Bloyet, Buchser Wj, Whelan Spj, Alford B, Elitza S. Theel, VanBlargan La, Liebeskind Mj, Paul W. Rothlauf, Rita E. Chen, Fremont Dh, Zhuoming Liu, and Stumpf S
- Subjects
Models, Molecular ,COVID-19 Vaccines ,medicine.drug_class ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Mutant ,Antibodies, Viral ,Monoclonal antibody ,Article ,Neutralization ,Epitope ,Mice ,Immune system ,Neutralization Tests ,Chlorocebus aethiops ,medicine ,Animals ,Humans ,Vero Cells ,Mice, Inbred BALB C ,biology ,SARS-CoV-2 ,Antibodies, Monoclonal ,COVID-19 ,Antibodies, Neutralizing ,Virology ,Amino Acid Substitution ,Mutation ,Spike Glycoprotein, Coronavirus ,Monoclonal ,biology.protein ,Receptors, Virus ,Female ,Angiotensin-Converting Enzyme 2 ,Antibody ,Protein Binding - Abstract
Although neutralizing antibodies against the SARS-CoV-2 spike (S) protein are a goal of COVID-19 vaccines and have received emergency use authorization as therapeutics, viral escape mutants could compromise their efficacy. To define the immune-selected mutational landscape in S protein, we used a VSV-eGFP-SARS-CoV-2-S chimeric virus and 19 neutralizing monoclonal antibodies (mAbs) against the receptor-binding domain (RBD) to generate 50 different escape mutants. The variants were mapped onto the RBD structure and evaluated for cross-resistance to mAbs and convalescent human sera. Each mAb had a unique resistance profile, although many shared residues within an epitope. Some variants (e.g., S477N) were resistant to neutralization by multiple mAbs, whereas others (e.g., E484K) escaped neutralization by convalescent sera, suggesting some humans induce a narrow repertoire of neutralizing antibodies. Comparing the antibody-mediated mutational landscape in S with sequence variation in circulating SARS-CoV-2, we define substitutions that may attenuate neutralizing immune responses in some humans.
- Published
- 2020
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