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SARS-CoV-2 Delta and Omicron variants evade population antibody response by mutations in a single spike epitope.

He, P ; Liu, B ; et al.
In: Nature microbiology, Jg. 7 (2022-10-01), Heft 10, S. 1635-1649
Online academicJournal
Zugriff:
View record at Springer (Volltext)

Population antibody response is thought to be important in selection of virus variants. We report that SARS-CoV-2 infection elicits a population immune response that is mediated by a lineage of VH1-69 germline antibodies. A representative antibody R1-32 from this lineage was isolated. By cryo-EM, we show that it targets a semi-cryptic epitope in the spike receptor-binding domain. Binding to this non-ACE2 competing epitope results in spike destruction, thereby inhibiting virus entry. On the basis of epitope location, neutralization mechanism and analysis of antibody binding to spike variants, we propose that recurrent substitutions at 452 and 490 are associated with immune evasion of the identified population antibody response. These substitutions, including L452R (present in the Delta variant), disrupt interactions mediated by the VH1-69-specific hydrophobic HCDR2 to impair antibody-antigen association, enabling variants to escape. The first Omicron variants were sensitive to antibody R1-32 but subvariants that harbour L452R quickly emerged and spread. Our results provide insights into how SARS-CoV-2 variants emerge and evade host immune responses.

(© 2022. The Author(s).)

Titel:
SARS-CoV-2 Delta and Omicron variants evade population antibody response by mutations in a single spike epitope.
Autor/in / Beteiligte Person: He, P ; Liu, B ; Gao, X ; Yan, Q ; Pei, R ; Sun, J ; Chen, Q ; Hou, R ; Li, Z ; Zhang, Y ; Zhao, J ; Sun, H ; Feng, B ; Wang, Q ; Yi, H ; Hu, P ; Li, P ; Chen, Z ; Niu, X ; Zhong, X ; Jin, L ; Liu, X ; Qu, K ; Ciazynska, KA ; Carter, AP ; Briggs, JAG ; Chen, J ; Liu, J ; Chen, X ; He, J ; Chen, L ; Xiong, X
Link:
Zeitschrift: Nature microbiology, Jg. 7 (2022-10-01), Heft 10, S. 1635-1649
Veröffentlichung: [London] : Nature Publishing Group, [2016]-, 2022
Medientyp: academicJournal
ISSN: 2058-5276 (electronic)
DOI: 10.1038/s41564-022-01235-4
Schlagwort:
  • Antibodies, Viral
  • Antibody Formation
  • Epitopes genetics
  • Humans
  • Mutation
  • Spike Glycoprotein, Coronavirus genetics
  • Spike Glycoprotein, Coronavirus metabolism
  • COVID-19
  • SARS-CoV-2 genetics
Sonstiges:
  • Nachgewiesen in: MEDLINE
  • Sprachen: English
  • Publication Type: Journal Article; Research Support, Non-U.S. Gov't
  • Language: English
  • [Nat Microbiol] 2022 Oct; Vol. 7 (10), pp. 1635-1649. <i>Date of Electronic Publication: </i>2022 Sep 23.
  • MeSH Terms: COVID-19* ; SARS-CoV-2* / genetics ; Antibodies, Viral ; Antibody Formation ; Epitopes / genetics ; Humans ; Mutation ; Spike Glycoprotein, Coronavirus / genetics ; Spike Glycoprotein, Coronavirus / metabolism
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  • Grant Information: 210711/Z/18/Z United Kingdom WT_ Wellcome Trust; MC_UP_A025_1011 United Kingdom MRC_ Medical Research Council
  • Substance Nomenclature: 0 (Antibodies, Viral) ; 0 (Epitopes) ; 0 (Spike Glycoprotein, Coronavirus) ; 0 (spike protein, SARS-CoV-2)
  • SCR Organism: SARS-CoV-2 variants
  • Entry Date(s): Date Created: 20220923 Date Completed: 20220930 Latest Revision: 20240306
  • Update Code: 20240306
  • PubMed Central ID: PMC9519457

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