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High-resolution profiling of pathways of escape for SARS-CoV-2 spike-binding antibodies.

Authors
  • Garrett, Meghan E1
  • Galloway, Jared2
  • Chu, Helen Y3
  • Itell, Hannah L1
  • Stoddard, Caitlin I4
  • Wolf, Caitlin R3
  • Logue, Jennifer K3
  • McDonald, Dylan3
  • Weight, Haidyn4
  • Matsen, Frederick A 4th5
  • Overbaugh, Julie6
  • 1 Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98102, USA; Molecular and Cellular Biology Graduate Program, University of Washington and Fred Hutchinson Cancer Research Center, Seattle, WA 98195, USA.
  • 2 Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98102, USA.
  • 3 Department of Medicine, University of Washington, Seattle, WA 98195, USA.
  • 4 Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98102, USA.
  • 5 Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98102, USA; Computational Biology Program, Fred Hutchinson Cancer Research Center, Seattle, WA 98102, USA.
  • 6 Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98102, USA; Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98102, USA. Electronic address: [email protected]
Type
Published Article
Journal
Cell
Publication Date
May 04, 2021
Identifiers
DOI: 10.1016/j.cell.2021.04.045
PMID: 34010620
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Defining long-term protective immunity to SARS-CoV-2 is one of the most pressing questions of our time and will require a detailed understanding of potential ways this virus can evolve to escape immune protection. Immune protection will most likely be mediated by antibodies that bind to the viral entry protein, spike (S). Here, we used Phage-DMS, an approach that comprehensively interrogates the effect of all possible mutations on binding to a protein of interest, to define the profile of antibody escape to the SARS-CoV-2 S protein using coronavirus disease 2019 (COVID-19) convalescent plasma. Antibody binding was common in two regions, the fusion peptide and the linker region upstream of the heptad repeat region 2. However, escape mutations were variable within these immunodominant regions. There was also individual variation in less commonly targeted epitopes. This study provides a granular view of potential antibody escape pathways and suggests there will be individual variation in antibody-mediated virus evolution. Copyright © 2021 Elsevier Inc. All rights reserved.

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