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

SARS-CoV-2 antibody escape bamlanivimab deep mutational scanning

Journal

Cell reports. Medicine
ISSN: 2666-3791
Titre abrégé: Cell Rep Med
Pays: United States
ID NLM: 101766894

Informations de publication

Date de publication:
20 04 2021
Historique:
received: 22 02 2021
revised: 22 03 2021
accepted: 26 03 2021
pubmed: 13 4 2021
medline: 13 4 2021
entrez: 12 4 2021
Statut: ppublish

Résumé

Monoclonal antibodies and antibody cocktails are a promising therapeutic and prophylaxis for coronavirus disease 2019 (COVID-19). However, ongoing evolution of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) can render monoclonal antibodies ineffective. Here, we completely map all of the 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 escapes LY-CoV016). In addition, 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 diversify the epitopes targeted by antibodies and antibody cocktails to make them more resilient to the antigenic evolution of SARS-CoV-2.

Identifiants

pubmed: 33842902
doi: 10.1016/j.xcrm.2021.100255
pii: S2666-3791(21)00071-9
pmc: PMC8020059
doi:

Types de publication

Journal Article

Langues

eng

Pagination

100255

Subventions

Organisme : NIAID NIH HHS
ID : R01 AI127893
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI140891
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI141707
Pays : United States

Commentaires et corrections

Type : UpdateOf

Informations de copyright

© 2021 The Author(s).

Déclaration de conflit d'intérêts

The authors declare no competing interests.

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Auteurs

Tyler N Starr (TN)

Basic Sciences and Computational Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.

Allison J Greaney (AJ)

Basic Sciences and Computational Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Department of Genome Sciences, University of Washington, Seattle, WA 98109, USA.
Medical Scientist Training Program, University of Washington, Seattle, WA 98109, USA.

Adam S Dingens (AS)

Basic Sciences and Computational Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.

Jesse D Bloom (JD)

Basic Sciences and Computational Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Department of Genome Sciences, University of Washington, Seattle, WA 98109, USA.
Howard Hughes Medical Institute, Seattle, WA 98109, USA.

Classifications MeSH