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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., Gao, X., Yan, Q., Pei, R., Sun, J., et al. (2022). SARS-CoV-2 Delta and Omicron variants evade population antibody response by mutations in a single spike epitope. Nature Microbiology, 7, 1635-1649. doi:10.1038/s41564-022-01235-4.

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 Creators:
He, Ping1, Author
Liu, Banghui1, Author
Gao, Xijie1, Author
Yan, Qihong1, Author
Pei, Rongjuan1, Author
Sun, Jing1, Author
Chen, Qiuluan1, Author
Hou, Ruitian1, Author
Li, Zimu1, Author
Zhang, Yanjun1, Author
Zhao, Jincun1, Author
Sun, Hao1, Author
Feng, Bo1, Author
Wang, Qian1, Author
Yi, Haisu1, Author
Hu, Peiyu1, Author
Li, Pingchao1, Author
Zhang, Yudi1, Author
Chen, Zhilong1, Author
Niu, Xuefeng1, Author
more..
Affiliations:
1external, ou_persistent22              
2Briggs, John / Cell and Virus Structure, Max Planck Institute of Biochemistry, Max Planck Society, ou_3344661              

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Free keywords: NEUTRALIZING ANTIBODIES; CRYO-EM; VACCINEMicrobiology;
 Abstract: 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.
Amino acid changes in a newly identified spike epitope enabled the Delta variant to evade a population antibody response.

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Language(s): eng - English
 Dates: 2022-09-23
 Publication Status: Published online
 Pages: 30
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Degree: -

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Title: Nature Microbiology
  Abbreviation : Nat. Microbiol.
Source Genre: Journal
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Publ. Info: London, UK : Nature Publishing Group
Pages: - Volume / Issue: 7 Sequence Number: - Start / End Page: 1635 - 1649 Identifier: ISSN: 2058-5276
CoNE: https://pure.mpg.de/cone/journals/resource/2058-5276