ArticleNature2014
Rapid development of broadly influenza neutralizing antibodies through redundant mutations.
Article in Nature, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 220 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
220 citing papers in PubMed, 313 citations in OpenAlex.
- Investigating the effect of AS03 adjuvant on the plasma cell repertoire following pH1N1 influenza vaccination.Scientific reports · 2016Trial
- Epistasis and pleiotropy constrain the evolution of cross-reactive breadth in a broadly neutralizing influenza antibody.PLoS biology · 2026Article
- CRISPR-mediated precise large fragment insertion in zygotes enables rapid generation of humanized immunoglobulin heavy-chain mice.Immunity · 2026Article
- The Influenza-Specific Immunoglobulin Repertoire - Nimble Yet Steeped in Tradition.Immunological reviews · 2026Review
- B cell αv integrin regulates tissue specialization and clonal expansion of lung germinal center and memory B cells after viral infection.Science advances · 2026Article
- Dyslipidemia-associated natural IgM improves oncolytic virus TILT-123 efficacy through antibody-dependent enhancement in solid tumors.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Naturally self-reactive B cells are poised to cross the selection barrier into autoimmune germinal centers.Cell reports · 2026Article
- Biophysical trade-offs in antibody evolution are resolved by conformation-mediated epistasis.bioRxiv : the preprint server for biology · 2026Article
- Population-level genomic analysis of immunoglobulin loci variation in rhesus macaques reveals extensive germline diversity.Immunity · 2026Article
- Characterization of two non-competing antibodies to influenza H3N2 hemagglutinin stem reveals its evolving antigenicity.Nature communications · 2025Article
- Structural basis for a potent human neutralizing antibody targeting a conserved epitope on the H7 hemagglutinin head.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Vulnerability in the breadth evolution of an influenza broadly neutralizing antibody.bioRxiv : the preprint server for biology · 2025Article
- Gene discovery and expression analysis of the B cell receptor repertoire in the domestic ferret model.Vaccine · 2025Article
- B cell αv integrin regulates tissue specialization and clonal expansion of lung germinal center and memory B cells after viral infection.bioRxiv : the preprint server for biology · 2025Article
- High-throughput synthesis and specificity characterization of natively paired influenza hemagglutinin antibodies with oPoolScience translational medicine · 2025Article
- Elucidating the characteristics and clonal evolutionary trajectory of influenza neuraminidase broadly reactive B cell.Science advances · 2025Article
- Review
- Structurally convergent antibodies derived from different vaccine strategies target the influenza virus HA anchor epitope with a subset of VNature communications · 2025Article
- Retrospective SARS-CoV-2 human antibody development trajectories are largely sparse and permissive.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Low-level human memory T and B cells recognising avian influenza hemagglutinins are poorly responsive to existing seasonal influenza vaccines.Clinical & translational immunology · 2025Article
160 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 3 institutions in 2 countries.
Funding
Abstract
The neutralizing antibody response to influenza virus is dominated by antibodies that bind to the globular head of haemagglutinin, which undergoes a continuous antigenic drift, necessitating the re-formulation of influenza vaccines on an annual basis. Recently, several laboratories have described a new class of rare influenza-neutralizing antibodies that target a conserved site in the haemagglutinin stem. Most of these antibodies use the heavy-chain variable region VH1-69 gene, and structural data demonstrate that they bind to the haemagglutinin stem through conserved heavy-chain complementarity determining region (HCDR) residues. However, the VH1-69 antibodies are highly mutated and are produced by some but not all individuals, suggesting that several somatic mutations may be required for their development. To address this, here we characterize 197 anti-stem antibodies from a single donor, reconstruct the developmental pathways of several VH1-69 clones and identify two key elements that are required for the initial development of most VH1-69 antibodies: a polymorphic germline-encoded phenylalanine at position 54 and a conserved tyrosine at position 98 in HCDR3. Strikingly, in most cases a single proline to alanine mutation at position 52a in HCDR2 is sufficient to confer high affinity binding to the selecting H1 antigen, consistent with rapid affinity maturation. Surprisingly, additional favourable mutations continue to accumulate, increasing the breadth of reactivity and making both the initial mutations and phenylalanine at position 54 functionally redundant. These results define VH1-69 allele polymorphism, rearrangement of the VDJ gene segments and single somatic mutations as the three requirements for generating broadly neutralizing VH1-69 antibodies and reveal an unexpected redundancy in the affinity maturation process.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.