Landscape analysis of escape variants identifies SARS-CoV-2 spike mutations that attenuate monoclonal and serum antibody neutralization.
Zhuoming LiuLaura A VanBlarganLouis-Marie BloyetPaul W RothlaufRita E ChenSpencer StumpfHaiyan ZhaoJohn M ErricoElitza S TheelMariel J LiebeskindBrynn AlfordWilliam J BuchserAli H EllebedyDaved H FremontMichael S. DiamondSean P J WhelanPublished in: bioRxiv : the preprint server for biology (2021)
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.
Keyphrases
- sars cov
- dengue virus
- respiratory syndrome coronavirus
- copy number
- immune response
- single cell
- binding protein
- endothelial cells
- public health
- amino acid
- emergency department
- genome wide
- stem cells
- healthcare
- small molecule
- cell therapy
- zika virus
- gene expression
- transcription factor
- toll like receptor
- multiple myeloma
- coronavirus disease
- inflammatory response
- dna methylation
- dna binding
- pluripotent stem cells