ArticleProceedings of the National Academy of Sciences of the United States of America2013
Redesign of a cross-reactive antibody to dengue virus with broad-spectrum activity and increased in vivo potency.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
What it found
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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
43 citing papers in PubMed.
- Safety and Preliminary Efficacy of Dengue Monoclonal Antibody in Adult Patients: A Randomized Clinical Trial.JAMA network open · 2026Trial
- Therapeutic approaches against dengue virus: current status of vaccines, antivirals, and monoclonal antibodies.Emerging microbes & infections · 2026Review
- Potent Cross-Serotype Dengue Neutralization with Low ADE by AG-Strand-Targeting Anti-EDIII Antibodies.ACS omega · 2026Article
- CD98hc-targeted antibody shuttles for central nervous system delivery with broad cross-species reactivity.Nature biomedical engineering · 2026Article
- Significantly enhancing human antibody affinity via deep learning and computational biology-guided single-point mutations.Briefings in bioinformatics · 2025Article
- A two-component cocktail of engineered DIII nanoparticles elicits broadly neutralizing antibody responses against dengue virus in mice.iScience · 2025Article
- Development and experimental validation of computational methods for human antibody affinity enhancement.Briefings in bioinformatics · 2024Article
- An Engineered N-Glycosylated Dengue Envelope Protein Domain III Facilitates Epitope-Directed Selection of Potently Neutralizing and Minimally Enhancing Antibodies.ACS infectious diseases · 2024Article
- Enhancing antibody affinity through experimental sampling of non-deleterious CDR mutations predicted by machine learning.Communications chemistry · 2023Article
- Review
- Improved HIV-1 neutralization breadth and potency of V2-apex antibodies by in silico design.Cell reports · 2023Article
- The validation of artificial anti-monkeypox antibodies by in silico and experimental approaches.Immunity, inflammation and disease · 2023Article
- Dengue virus neutralizing antibody: a review of targets, cross-reactivity, and antibody-dependent enhancement.Frontiers in immunology · 2023Review
- Learned features of antibody-antigen binding affinity.Frontiers in molecular biosciences · 2023Article
- Article
- Charged Residue Implantation Improves the Affinity of a Cross-Reactive Dengue Virus Antibody.International journal of molecular sciences · 2022Article
- Residue-based pharmacophore approaches to study protein-protein interactions.Current opinion in structural biology · 2021Review
- Machine Learning Detects Anti-DENV Signatures in Antibody Repertoire Sequences.Frontiers in artificial intelligence · 2021Article
- Prospective Artificial Intelligence to Dissect the Dengue Immune Response and Discover Therapeutics.Frontiers in immunology · 2021Review
- Adaptive Immunity to Dengue Virus: Slippery Slope or Solid Ground for Rational Vaccine Design?Pathogens (Basel, Switzerland) · 2020Review
Corrections and comments
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Authors and funding
9 authors.
Funding
Abstract
Affinity improvement of proteins, including antibodies, by computational chemistry broadly relies on physics-based energy functions coupled with refinement. However, achieving significant enhancement of binding affinity (>10-fold) remains a challenging exercise, particularly for cross-reactive antibodies. We describe here an empirical approach that captures key physicochemical features common to antigen-antibody interfaces to predict protein-protein interaction and mutations that confer increased affinity. We apply this approach to the design of affinity-enhancing mutations in 4E11, a potent cross-reactive neutralizing antibody to dengue virus (DV), without a crystal structure. Combination of predicted mutations led to a 450-fold improvement in affinity to serotype 4 of DV while preserving, or modestly increasing, affinity to serotypes 1-3 of DV. We show that increased affinity resulted in strong in vitro neutralizing activity to all four serotypes, and that the redesigned antibody has potent antiviral activity in a mouse model of DV challenge. Our findings demonstrate an empirical computational chemistry approach for improving protein-protein docking and engineering antibody affinity, which will help accelerate the development of clinically relevant antibodies.
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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.