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Complete map of SARS-CoV-2 RBD mutations that escape the monoclonal antibody LY-CoV555 and its cocktail with LY-CoV016

View ORCID ProfileTyler N. Starr, View ORCID ProfileAllison J. Greaney, View ORCID ProfileAdam S. Dingens, View ORCID ProfileJesse D. Bloom
doi: https://doi.org/10.1101/2021.02.17.431683
Tyler N. Starr
1Basic Sciences and Computational Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109
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Allison J. Greaney
1Basic Sciences and Computational Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109
2Department of Genome Sciences, University of Washington, Seattle, WA 98109
3Medical Scientist Training Program, University of Washington, Seattle, WA 98109
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Adam S. Dingens
1Basic Sciences and Computational Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109
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Jesse D. Bloom
1Basic Sciences and Computational Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109
2Department of Genome Sciences, University of Washington, Seattle, WA 98109
4Howard Hughes Medical Institute, Seattle, WA 98109
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  • For correspondence: jbloom@fredhutch.org
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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.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • https://jbloomlab.github.io/SARS-CoV-2-RBD_MAP_LY-CoV555/

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted February 22, 2021.
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Complete map of SARS-CoV-2 RBD mutations that escape the monoclonal antibody LY-CoV555 and its cocktail with LY-CoV016
Tyler N. Starr, Allison J. Greaney, Adam S. Dingens, Jesse D. Bloom
bioRxiv 2021.02.17.431683; doi: https://doi.org/10.1101/2021.02.17.431683
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Complete map of SARS-CoV-2 RBD mutations that escape the monoclonal antibody LY-CoV555 and its cocktail with LY-CoV016
Tyler N. Starr, Allison J. Greaney, Adam S. Dingens, Jesse D. Bloom
bioRxiv 2021.02.17.431683; doi: https://doi.org/10.1101/2021.02.17.431683

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