ArticleeLife2023
Hierarchical sequence-affinity landscapes shape the evolution of breadth in an anti-influenza receptor binding site antibody.
Article in eLife, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
22 citing papers in PubMed.
- Article
- Amplicon/Protein Bead Display enables quantitativebioRxiv : the preprint server for biology · 2026Article
- Entrenchment of germline amino-acid differences in antibody affinity maturation.bioRxiv : the preprint server for biology · 2026Article
- Phase diagrams for biophysical fitness landscape design.bioRxiv : the preprint server for biology · 2026Article
- Biophysical trade-offs in antibody evolution are resolved by conformation-mediated epistasis.bioRxiv : the preprint server for biology · 2026Article
- Experimental evolution in an era of molecular manipulation.Nature reviews. Genetics · 2026Review
- Epistatic drift in protein evolution.Current opinion in genetics & development · 2025Review
- Article
- A combinatorial mutational map of active non-native protein kinases by deep learning guided sequence design.bioRxiv : the preprint server for biology · 2025Article
- Antigenic drift expands influenza viral escape pathways from recalled humoral immunity.Immunity · 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
- Epistatic hotspots organize antibody fitness landscape and boost evolvability.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- The simplicity of protein sequence-function relationships.Nature communications · 2024Article
- A library-on-library screen reveals the breadth expansion landscape of a broadly neutralizing betacoronavirus antibody.bioRxiv : the preprint server for biology · 2024Article
- Article
- Article
- An integrated technology for quantitative wide mutational scanning of human antibody Fab libraries.Nature communications · 2024Article
- The simplicity of protein sequence-function relationships.bioRxiv : the preprint server for biology · 2024Article
- Protein sequence landscapes are not so simple: on reference-free versus reference-based inference.bioRxiv : the preprint server for biology · 2024Article
- An integrated technology for quantitative wide mutational scanning of human antibody Fab libraries.bioRxiv : the preprint server for biology · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors.
Funding
Abstract
Broadly neutralizing antibodies (bnAbs) that neutralize diverse variants of a particular virus are of considerable therapeutic interest. Recent advances have enabled us to isolate and engineer these antibodies as therapeutics, but eliciting them through vaccination remains challenging, in part due to our limited understanding of how antibodies evolve breadth. Here, we analyze the landscape by which an anti-influenza receptor binding site (RBS) bnAb, CH65, evolved broad affinity to diverse H1 influenza strains. We do this by generating an antibody library of all possible evolutionary intermediates between the unmutated common ancestor (UCA) and the affinity-matured CH65 antibody and measure the affinity of each intermediate to three distinct H1 antigens. We find that affinity to each antigen requires a specific set of mutations - distributed across the variable light and heavy chains - that interact non-additively (i.e., epistatically). These sets of mutations form a hierarchical pattern across the antigens, with increasingly divergent antigens requiring additional epistatic mutations beyond those required to bind less divergent antigens. We investigate the underlying biochemical and structural basis for these hierarchical sets of epistatic mutations and find that epistasis between heavy chain mutations and a mutation in the light chain at the V
Indexed as
Identifiers
What OpenQuestion holds
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.