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Complete Mapping of Mutations to the SARS-CoV-2 Spike Receptor-Binding Domain that Escape Antibody Recognition.
Greaney, Allison J; Starr, Tyler N; Gilchuk, Pavlo; Zost, Seth J; Binshtein, Elad; Loes, Andrea N; Hilton, Sarah K; Huddleston, John; Eguia, Rachel; Crawford, Katharine H D; Dingens, Adam S; Nargi, Rachel S; Sutton, Rachel E; Suryadevara, Naveenchandra; Rothlauf, Paul W; Liu, Zhuoming; Whelan, Sean P J; Carnahan, Robert H; Crowe, James E; Bloom, Jesse D.
  • Greaney AJ; Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA; Department of Genome Sciences & Medical Scientist Training Program, University of Washington, Seattle, WA 98195, USA.
  • Starr TN; Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
  • Gilchuk P; Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
  • Zost SJ; Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
  • Binshtein E; Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
  • Loes AN; Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA; Howard Hughes Medical Institute, Seattle, WA 98109, USA.
  • Hilton SK; Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
  • Huddleston J; Molecular and Cell Biology, University of Washington, Seattle, WA 98195 USA.
  • Eguia R; Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
  • Crawford KHD; Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA; Department of Genome Sciences & Medical Scientist Training Program, University of Washington, Seattle, WA 98195, USA.
  • Dingens AS; Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
  • Nargi RS; Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
  • Sutton RE; Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
  • Suryadevara N; Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
  • Rothlauf PW; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA; Program in Virology, Harvard Medical School, Boston, MA 02115, USA.
  • Liu Z; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
  • Whelan SPJ; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
  • Carnahan RH; Howard Hughes Medical Institute, Seattle, WA 98109, USA; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
  • Crowe JE; Howard Hughes Medical Institute, Seattle, WA 98109, USA; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN 37232, USA. Electronic address: james.crowe@vu
  • Bloom JD; Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA; Department of Genome Sciences & Medical Scientist Training Program, University of Washington, Seattle, WA 98195, USA; Howard Hughes Medical Institute, Seattle, WA 98109, USA. Electronic address: jbloom@fredh
Cell Host Microbe ; 29(1): 44-57.e9, 2021 01 13.
Article in English | MEDLINE | ID: covidwho-1385265
Preprint
This scientific journal article is probably based on a previously available preprint. It has been identified through a machine matching algorithm, human confirmation is still pending.
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ABSTRACT
Antibodies targeting the SARS-CoV-2 spike receptor-binding domain (RBD) are being developed as therapeutics and are a major contributor to neutralizing antibody responses elicited by infection. Here, we describe a deep mutational scanning method to map how all amino-acid mutations in the RBD affect antibody binding and apply this method to 10 human monoclonal antibodies. The escape mutations cluster on several surfaces of the RBD that broadly correspond to structurally defined antibody epitopes. However, even antibodies targeting the same surface often have distinct escape mutations. The complete escape maps predict which mutations are selected during viral growth in the presence of single antibodies. They further enable the design of escape-resistant antibody cocktails-including cocktails of antibodies that compete for binding to the same RBD surface but have different escape mutations. Therefore, complete escape-mutation maps enable rational design of antibody therapeutics and assessment of the antigenic consequences of viral evolution.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Spike Glycoprotein, Coronavirus / SARS-CoV-2 Type of study: Prognostic study Limits: Humans Language: English Journal: Cell Host Microbe Journal subject: Microbiology Year: 2021 Document Type: Article Affiliation country: J.CHOM.2020.11.007

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Spike Glycoprotein, Coronavirus / SARS-CoV-2 Type of study: Prognostic study Limits: Humans Language: English Journal: Cell Host Microbe Journal subject: Microbiology Year: 2021 Document Type: Article Affiliation country: J.CHOM.2020.11.007