ArticleEmerging microbes & infections2022
Shared IGHV1-69-encoded neutralizing antibodies contribute to the emergence of L452R substitution in SARS-CoV-2 variants.
Article in Emerging microbes & infections, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 31 citations in OpenAlex.
- R1-32-like public antibodies acquire tolerance to SARS-CoV-2 antigenic drift through somatic hypermutation.PLoS biology · 2026Article
- Systems-Scale Structural Modeling Reveals the Germline Architecture of Immunodominance.bioRxiv : the preprint server for biology · 2026Article
- Ad5-boosted COVID-19 vaccine reduces symptomatic BA.5 infection via cross-neutralizing antibodies and NK cell immunity.BMC medicine · 2025Article
- Explore antibody repertoire in the era of AI.Acta biochimica et biophysica Sinica · 2025Article
- Bio-Inspired Mamba for Antibody-Antigen Interaction Prediction.Biomolecules · 2025Article
- SARS-related coronavirus S-protein structures reveal synergistic RBM interactions underpinning high-affinity human ACE2 binding.Science advances · 2025Article
- Ancestral SARS-CoV-2 immune imprinting persists on RBD but not NTD after sequential Omicron infections.iScience · 2025Article
- A human monoclonal antibody neutralizing SARS-CoV-2 Omicron variants containing the L452R mutation.Journal of virology · 2024Article
- Deep immunoglobulin repertoire sequencing depicts a comprehensive atlas of spike-specific antibody lineages shared among COVID-19 convalescents.Emerging microbes & infections · 2024Article
- Article
- Diverse BCR usage and T cell activation induced by different COVID-19 sequential vaccinations.mBio · 2024Article
- Antibodies utilizing VL6-57 light chains target a convergent cryptic epitope on SARS-CoV-2 spike protein and potentially drive the genesis of Omicron variants.Nature communications · 2024Article
- Article
- An ancestral SARS-CoV-2 vaccine induces anti-Omicron variants antibodies by hypermutation.Nature communications · 2024Article
- Nanobody repertoire generated against the spike protein of ancestral SARS-CoV-2 remains efficacious against the rapidly evolving virus.bioRxiv : the preprint server for biology · 2024Article
- Broadly neutralizing antibodies derived from the earliest COVID-19 convalescents protect mice from SARS-CoV-2 variants challenge.Signal transduction and targeted therapy · 2023Article
- Monovalent Omicron COVID-19 vaccine triggers superior neutralizing antibody responses against Omicron subvariants than Delta and Omicron bivalent vaccine.Human vaccines & immunotherapeutics · 2023Article
- Somatically hypermutated antibodies isolated from SARS-CoV-2 Delta infected patients cross-neutralize heterologous variants.Nature communications · 2023Article
- Transcriptional Profiles Analysis of COVID-19 and Malaria Patients Reveals Potential Biomarkers in Children.bioRxiv : the preprint server for biology · 2022Article
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Authors and funding
15 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
SARS-CoV-2 variants continue to emerge facing established herd immunity. L452R, previously featured in the Delta variant, quickly emerged in Omicron subvariants, including BA.4/BA.5, implying a continued selection pressure on this residue. The underlying links between spike mutations and their selective pressures remain incompletely understood. Here, by analyzing 221 structurally characterized antibodies, we found that IGHV1-69-encoded antibodies preferentially contact L452 using germline-encoded hydrophobic residues at the tip of HCDR2 loop. Whereas somatic hypermutations or VDJ rearrangements are required to acquire L452-contacting hydrophobic residues for non-IGHV1-69 encoded antibodies. Antibody repertoire analysis revealed that IGHV1-69 L452-contacting antibody lineages are commonly induced among COVID-19 convalescents but non-IGHV1-69 encoded antibodies exhibit limited prevalence. In addition, we experimentally demonstrated that L452R renders most published IGHV1-69 antibodies ineffective. Furthermore, we found that IGHV1-69 L452-contacting antibodies are enriched in convalescents experienced Omicron BA.1 (without L452R) breakthrough infections but rarely found in Delta (with L452R) breakthrough infections. Taken together, these findings support that IGHV1-69 population antibodies contribute to selection pressure for L452 substitution. This study thus provides a better understanding of SARS-CoV-2 variant genesis and immune evasion.
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