Complete map of SARS-CoV-2 RBD mutations that escape the monoclonal antibody LY-CoV555 and its cocktail with LY-CoV016
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Abstract
Monoclonal antibodies and antibody cocktails are a promising therapeutic and prophylaxis for COVID-19. However, ongoing evolution of SARS-CoV-2 can render monoclonal antibodies ineffective. Here we completely map all mutations to the SARS-CoV-2 spike receptor binding domain (RBD) that escape binding by a leading monoclonal antibody, LY-CoV555, and its cocktail combination with LY-CoV016. Individual mutations that escape binding by each antibody are combined in the circulating B.1.351 and P.1 SARS-CoV-2 lineages (E484K escapes LY-CoV555, K417N/T escape LY-CoV016). Additionally, the L452R mutation in the B.1.429 lineage escapes LY-CoV555. Furthermore, we identify single amino acid changes that escape the combined LY-CoV555+LY-CoV016 cocktail. We suggest that future efforts should diversify the epitopes targeted by antibodies and antibody cocktails to make them more resilient to antigenic evolution of SARS-CoV-2.
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SciScore for 10.1101/2021.02.17.431683: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
NIH rigor criteria are not applicable to paper type.Table 2: Resources
Antibodies Sentences Resources Data and Code Availability: Antibodies: The LY-CoV555 antibody variable domain sequences were acquired from the LY-CoV555 crystal structure file (PDB 7KMG, [4]), which was generously shared by Bryan Jones and Eli Lilly and Co. prior to its publication. LY-CoV555suggested: NoneCells were then incubated with 1:200 PE-conjugated goat anti-human-IgG (Jackson ImmunoResearch 109-115-098) to label for bound antibody and 1:100 FITC-conjugated anti-Myc (Immunology Consultants Lab, CYMC-45F) to label for RBD surface expression. anti-human-IgGsuggested: Noneanti-Mycsuggested: NonePlasmid was purified from pre-sort … SciScore for 10.1101/2021.02.17.431683: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
NIH rigor criteria are not applicable to paper type.Table 2: Resources
Antibodies Sentences Resources Data and Code Availability: Antibodies: The LY-CoV555 antibody variable domain sequences were acquired from the LY-CoV555 crystal structure file (PDB 7KMG, [4]), which was generously shared by Bryan Jones and Eli Lilly and Co. prior to its publication. LY-CoV555suggested: NoneCells were then incubated with 1:200 PE-conjugated goat anti-human-IgG (Jackson ImmunoResearch 109-115-098) to label for bound antibody and 1:100 FITC-conjugated anti-Myc (Immunology Consultants Lab, CYMC-45F) to label for RBD surface expression. anti-human-IgGsuggested: Noneanti-Mycsuggested: NonePlasmid was purified from pre-sort and antibody-escape populations, and mutant frequencies pre- and post-sort were determined by Illumina sequencing of variant-identifier barcodes, exactly as described in Starr et al. [20]. antibody-escape populations ,suggested: NoneThe escape fraction of each library variant was determined as the fraction of cells carrying a particular barcode that were sorted into the antibody-escape bin, using the equation given in Greaney et al. [18]. antibody-escape binsuggested: NoneSoftware and Algorithms Sentences Resources 3, escape scores were mapped to PDB b-factors and visualized in PyMol using antibody-bound RBD structures PDB 7KMG [4] and PDB 7C01 [22]. PyMolsuggested: (PyMOL, RRID:SCR_000305)Results from OddPub: Thank you for sharing your code and data.
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
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