ArticleeLife2021
Binding affinity landscapes constrain the evolution of broadly neutralizing anti-influenza antibodies.
Article in eLife, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 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
57 citing papers in PubMed, 82 citations in OpenAlex.
- Epistasis and pleiotropy constrain the evolution of cross-reactive breadth in a broadly neutralizing influenza antibody.PLoS biology · 2026Article
- Article
- PreFold-dG: estimating binding affinity of protein-protein interaction from intermediate representations of protein folding model.Bioinformatics (Oxford, England) · 2026Article
- Amplicon/Protein Bead Display enables quantitativebioRxiv : the preprint server for biology · 2026Article
- USP-ddG: a unified structural paradigm with data efficacy and mixture-of-experts for predicting mutational effects on protein-protein interactions.Bioinformatics (Oxford, England) · 2026Article
- Entrenchment of germline amino-acid differences in antibody affinity maturation.bioRxiv : the preprint server for biology · 2026Article
- Epistasis and background dependence in the evolution of Omicron variants of the SARS-CoV-2 spike protein.Molecular biology and evolution · 2026Article
- Biophysical trade-offs in antibody evolution are resolved by conformation-mediated epistasis.bioRxiv : the preprint server for biology · 2026Article
- Article
- Functional bottlenecks can emerge from non-epistatic underlying traits.PLoS computational biology · 2026Article
- Predicting viral sensitivity to antibodies using genetic sequences and antibody similarities.PLoS computational biology · 2026Article
- Paraplume: A fast and accurate antibody paratope prediction method provides insights into repertoire-scale binding dynamics.PLoS computational biology · 2026Article
- Experimental evolution in an era of molecular manipulation.Nature reviews. Genetics · 2026Review
- Fitness Landscape for Antibodies 2: Benchmarking Reveals That Protein AI Models Cannot Yet Consistently Predict Developability Properties.bioRxiv : the preprint server for biology · 2025Article
- Article
- Epistatic drift in protein evolution.Current opinion in genetics & development · 2025Review
- Epistasis and background dependence in the evolution of Omicron variants of the SARS-CoV-2 Spike protein.bioRxiv : the preprint server for biology · 2025Article
- Vulnerability in the breadth evolution of an influenza broadly neutralizing antibody.bioRxiv : the preprint server for biology · 2025Article
- Article
- The structure of an ancient genotype-phenotype map shaped the functional evolution of a protein family.Nature ecology & evolution · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Over the past two decades, several broadly neutralizing antibodies (bnAbs) that confer protection against diverse influenza strains have been isolated. Structural and biochemical characterization of these bnAbs has provided molecular insight into how they bind distinct antigens. However, our understanding of the evolutionary pathways leading to bnAbs, and thus how best to elicit them, remains limited. Here, we measure equilibrium dissociation constants of combinatorially complete mutational libraries for two naturally isolated influenza bnAbs (CR9114, 16 heavy-chain mutations; CR6261, 11 heavy-chain mutations), reconstructing all possible evolutionary intermediates back to the unmutated germline sequences. We find that these two libraries exhibit strikingly different patterns of breadth: while many variants of CR6261 display moderate affinity to diverse antigens, those of CR9114 display appreciable affinity only in specific, nested combinations. By examining the extensive pairwise and higher order epistasis between mutations, we find key sites with strong synergistic interactions that are highly similar across antigens for CR6261 and different for CR9114. Together, these features of the binding affinity landscapes strongly favor sequential acquisition of affinity to diverse antigens for CR9114, while the acquisition of breadth to more similar antigens for CR6261 is less constrained. These results, if generalizable to other bnAbs, may explain the molecular basis for the widespread observation that sequential exposure favors greater breadth, and such mechanistic insight will be essential for predicting and eliciting broadly protective immune responses.
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.