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Comprehensive mapping of mutations in the SARS-CoV-2 receptor-binding domain that affect recognition by polyclonal human plasma antibodies.
Greaney, Allison J; Loes, Andrea N; Crawford, Katharine H D; Starr, Tyler N; Malone, Keara D; Chu, Helen Y; Bloom, Jesse D.
  • Greaney AJ; Basic Sciences Division and Computational Biology Program, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA; Department of Genome Sciences & Medical Scientist Training Program, University of Washington, Seattle, WA 98195, USA.
  • Loes AN; Basic Sciences Division and Computational Biology Program, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA; Howard Hughes Medical Institute, Seattle, WA 98109, USA.
  • Crawford KHD; Basic Sciences Division and Computational Biology Program, 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 and Computational Biology Program, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA; Howard Hughes Medical Institute, Seattle, WA 98109, USA.
  • Malone KD; Basic Sciences Division and Computational Biology Program, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
  • Chu HY; Division of Allergy and Infectious Diseases, University of Washington, Seattle, WA, USA.
  • Bloom JD; Basic Sciences Division and Computational Biology Program, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA; Howard Hughes Medical Institute, Seattle, WA 98109, USA. Electronic address: jbloom@fredhutch.org.
Cell Host Microbe ; 29(3): 463-476.e6, 2021 03 10.
Article in English | MEDLINE | ID: covidwho-1071171
Preprint
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Semantic information from SemMedBD (by NLM)
1. Convalescent plasma LOCATION_OF Antibodies
Subject
Convalescent plasma
Predicate
LOCATION_OF
Object
Antibodies
2. Mutation AFFECTS Antibodies
Subject
Mutation
Predicate
AFFECTS
Object
Antibodies
3. Plasma LOCATION_OF Polyclonal antibody
Subject
Plasma
Predicate
LOCATION_OF
Object
Polyclonal antibody
4. Epitopes AFFECTS Mutation
Subject
Epitopes
Predicate
AFFECTS
Object
Mutation
5. immunoglobulin binding PROCESS_OF Persons
Subject
immunoglobulin binding
Predicate
PROCESS_OF
Object
Persons
6. Mutation AFFECTS Polyclonal antibody
Subject
Mutation
Predicate
AFFECTS
Object
Polyclonal antibody
7. Mutation DISRUPTS immunoglobulin binding
Subject
Mutation
Predicate
DISRUPTS
Object
immunoglobulin binding
8. Convalescent plasma LOCATION_OF Antibodies
Subject
Convalescent plasma
Predicate
LOCATION_OF
Object
Antibodies
9. Mutation AFFECTS Antibodies
Subject
Mutation
Predicate
AFFECTS
Object
Antibodies
10. Plasma LOCATION_OF Polyclonal antibody
Subject
Plasma
Predicate
LOCATION_OF
Object
Polyclonal antibody
11. Epitopes AFFECTS Mutation
Subject
Epitopes
Predicate
AFFECTS
Object
Mutation
12. immunoglobulin binding PROCESS_OF Persons
Subject
immunoglobulin binding
Predicate
PROCESS_OF
Object
Persons
13. Mutation AFFECTS Polyclonal antibody
Subject
Mutation
Predicate
AFFECTS
Object
Polyclonal antibody
14. Mutation DISRUPTS immunoglobulin binding
Subject
Mutation
Predicate
DISRUPTS
Object
immunoglobulin binding
ABSTRACT
The evolution of SARS-CoV-2 could impair recognition of the virus by human antibody-mediated immunity. To facilitate prospective surveillance for such evolution, we map how convalescent plasma antibodies are impacted by all mutations to the spike's receptor-binding domain (RBD), the main target of plasma neutralizing activity. Binding by polyclonal plasma antibodies is affected by mutations in three main epitopes in the RBD, but longitudinal samples reveal that the impact of these mutations on antibody binding varies substantially both among individuals and within the same individual over time. Despite this inter- and intra-person heterogeneity, the mutations that most reduce antibody binding usually occur at just a few sites in the RBD's receptor-binding motif. The most important site is E484, where neutralization by some plasma is reduced >10-fold by several mutations, including one in the emerging 20H/501Y.V2 and 20J/501Y.V3 SARS-CoV-2 lineages. Going forward, these plasma escape maps can inform surveillance of SARS-CoV-2 evolution.
Subject(s)
Keywords

Full text: Available Collection: International databases Database: MEDLINE Main subject: Antibodies, Neutralizing / Spike Glycoprotein, Coronavirus / SARS-CoV-2 / COVID-19 / Antibodies, Viral Type of study: Observational study Limits: Adult / Aged / Female / Humans / Male / Middle aged / Young adult Language: English Journal: Cell Host Microbe Journal subject: Microbiology Year: 2021 Document Type: Article Affiliation country: J.chom.2021.02.003

Full text: Available Collection: International databases Database: MEDLINE Main subject: Antibodies, Neutralizing / Spike Glycoprotein, Coronavirus / SARS-CoV-2 / COVID-19 / Antibodies, Viral Type of study: Observational study Limits: Adult / Aged / Female / Humans / Male / Middle aged / Young adult Language: English Journal: Cell Host Microbe Journal subject: Microbiology Year: 2021 Document Type: Article Affiliation country: J.chom.2021.02.003