ArticleNature microbiology2022
SARS-CoV-2 Delta and Omicron variants evade population antibody response by mutations in a single spike epitope.
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Article in Nature microbiology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers, 1 of them a synthesis that pooled it.
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53citing papers in PubMed, 1 pooled it
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Who cites it
53 citing papers in PubMed, 1 synthesis or guideline pooled it, 80 citations in OpenAlex.
- Mucosal immune response in biology, disease prevention and treatment.Signal transduction and targeted therapy · 2025Pooled it
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- What Antibody Repertoires See: Structural and Immunogenetic Insights Into Influenza A Virus Hemagglutinin Recognition.Immunological reviews · 2026Review
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- Structural basis for sarbecovirus Rc-o319 spike adaptation to Rhinolophus cornutus Bat ACE2 and constraints on switching to human ACE2.PLoS pathogens · 2026Article
- Refined phenotyping of vaccine responses reveals transcriptomic determinants of neutralizing antibody heterogeneity.NPJ vaccines · 2026Article
- Clonal interference and changing selective pressures shape the escape of SARS-CoV-2 from hundreds of antibodies.Virus evolution · 2026Article
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- Perspective Overview of Changing Population Immunity to COVID-19 in the Context of Infection, Vaccination, and Emerging SARS-CoV-2 Variants.Pathogens (Basel, Switzerland) · 2025Review
- Omicron Subvariants Infection Kinetics and Nirmatrelvir Efficacy in Transgenic K18-hACE2 Mice.International journal of molecular sciences · 2025Article
- Neutralizing Antibodies vs. Viruses: Interacting Mechanisms and Escape Tactics.Microorganisms · 2025Review
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- Omicron Subvariants Infection Kinetics and Nirmatrelvir Efficacy in Transgenic K18-hACE2 Mice.bioRxiv : the preprint server for biology · 2025Article
- SARS-CoV-2 spike protein: structure, viral entry and variants.Nature reviews. Microbiology · 2025Review
- A Smart Single-Loop-Mediated Isothermal Amplification Facilitates Flexible SNP Probe Design for On-Site Rapid Differentiation of SARS-CoV-2 Omicron Variants.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Intrinsic immunogenicity is a major determinant of type-specific responses in SARS-CoV-2 infections.Nature immunology · 2025Article
- SARS-related coronavirus S-protein structures reveal synergistic RBM interactions underpinning high-affinity human ACE2 binding.Science advances · 2025Article
- Reaction Pathway Differentiation Enabled Fingerprinting Signal for Single Nucleotide Variant Detection.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- NIEAs elicited by wild-type SARS-CoV-2 primary infection fail to enhance the infectivity of Omicron variants.Virology journal · 2025Article
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Authors and funding
33 authors at 7 institutions in 4 countries.
Ping He *State Key Laboratory of Respiratory Disease, CAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangdong Provincial Key Laboratory of Biocomputing, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
Banghui Liu *State Key Laboratory of Respiratory Disease, CAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangdong Provincial Key Laboratory of Biocomputing, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
Xijie Gao *Bioland Laboratory (Guangzhou Regenerative Medicine and Health - Guangdong Laboratory), Guangzhou, China.ORCID http://orcid.org/0000-0002-0602-4690
Qihong Yan *State Key Laboratory of Respiratory Disease, CAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangdong Provincial Key Laboratory of Biocomputing, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
Rongjuan Pei *State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, China.
Jing SunState Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Qiuluan ChenBioland Laboratory (Guangzhou Regenerative Medicine and Health - Guangdong Laboratory), Guangzhou, China.
Ruitian HouState Key Laboratory of Respiratory Disease, CAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangdong Provincial Key Laboratory of Biocomputing, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
Zimu LiState Key Laboratory of Respiratory Disease, CAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangdong Provincial Key Laboratory of Biocomputing, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
Yanjun ZhangState Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Jincun ZhaoState Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.ORCID http://orcid.org/0000-0003-2515-5589
Hao SunState Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, China.
Bo FengSchool of Biomedical Sciences, Huaqiao University, Quanzhou, China.
Qian WangState Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Haisu YiState Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Peiyu HuState Key Laboratory of Respiratory Disease, CAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangdong Provincial Key Laboratory of Biocomputing, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
Pingchao LiState Key Laboratory of Respiratory Disease, CAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangdong Provincial Key Laboratory of Biocomputing, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
Yudi ZhangState Key Laboratory of Respiratory Disease, CAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangdong Provincial Key Laboratory of Biocomputing, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
Zhilong ChenSchool of Biomedical Sciences, Huaqiao University, Quanzhou, China.
Xuefeng NiuState Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Xiaolin ZhongBioland Laboratory (Guangzhou Regenerative Medicine and Health - Guangdong Laboratory), Guangzhou, China.
Liang JinBioland Laboratory (Guangzhou Regenerative Medicine and Health - Guangdong Laboratory), Guangzhou, China.
Xiaofeng LiuAngitia Biopharmaceuticals, Guangzhou, China.
Kun QuInfectious Diseases Translational Research Programme, Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.ORCID http://orcid.org/0000-0002-3152-2237
Katarzyna A CiazynskaStructural Studies Division, Medical Research Council Laboratory of Molecular Biology, Cambridge, UK.ORCID http://orcid.org/0000-0002-9899-2428
Andrew P CarterStructural Studies Division, Medical Research Council Laboratory of Molecular Biology, Cambridge, UK.ORCID http://orcid.org/0000-0001-7292-5430
John A G BriggsStructural Studies Division, Medical Research Council Laboratory of Molecular Biology, Cambridge, UK.ORCID http://orcid.org/0000-0003-3990-6910
Jizheng ChenState Key Laboratory of Respiratory Disease, CAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangdong Provincial Key Laboratory of Biocomputing, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
Jinsong LiuState Key Laboratory of Respiratory Disease, CAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangdong Provincial Key Laboratory of Biocomputing, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.ORCID http://orcid.org/0000-0003-2317-0558
Xinwen ChenState Key Laboratory of Respiratory Disease, CAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangdong Provincial Key Laboratory of Biocomputing, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China. chen_xinwen@gibh.ac.cn.ORCID http://orcid.org/0000-0002-4052-8155
Jun HeState Key Laboratory of Respiratory Disease, CAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangdong Provincial Key Laboratory of Biocomputing, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China. he_jun@gibh.ac.cn.ORCID http://orcid.org/0000-0003-0270-9729
Ling ChenState Key Laboratory of Respiratory Disease, CAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangdong Provincial Key Laboratory of Biocomputing, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China. chen_ling@gibh.ac.cn.ORCID http://orcid.org/0000-0003-1485-1626
Xiaoli XiongState Key Laboratory of Respiratory Disease, CAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangdong Provincial Key Laboratory of Biocomputing, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China. xiong_xiaoli@gibh.ac.cn.ORCID http://orcid.org/0000-0002-4632-9122
Chinese Academy of Sciences · CNFirst Affiliated Hospital of Guangzhou Medical University · CNGuangzhou Regenerative Medicine and Health Guangdong Laboratory · CNGuangzhou Institutes of Biomedicine and Health · CNMRC Laboratory of Molecular Biology · GBHuaqiao University · CNNational University of Singapore · SG
Funding
Medical Research Council MC_UP_A025_1011Wellcome Trust 210711/Z/18/Z
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.
Indexed as
COVID-19SARS-CoV-2Antibodies, ViralAntibody FormationEpitopesHumansMutationSpike Glycoprotein, CoronavirusAntibodies, ViralEpitopesSpike Glycoprotein, Coronavirusspike protein, SARS-CoV-2
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