ArticleThe Journal of biological chemistry2011
Affinity maturation to improve human monoclonal antibody neutralization potency and breadth against hepatitis C virus.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 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
23 citing papers in PubMed, 33 citations in OpenAlex.
- Article
- Generation and Next-Generation Sequencing-Based Characterization of a Large Human Combinatorial Antibody Library.International journal of molecular sciences · 2023Article
- Structural and Biophysical Characterization of the HCV E1E2 Heterodimer for Vaccine Development.Viruses · 2021Review
- Review
- Review
- Design of a native-like secreted form of the hepatitis C virus E1E2 heterodimer.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Envelope-Specific IgG3 and IgG1 Responses Are Associated with Clearance of Acute Hepatitis C Virus Infection.Viruses · 2020Article
- Improvement in affinity and thermostability of a fully human antibody against interleukin-17A by yeast-display technology and CDR grafting.Acta pharmaceutica Sinica. B · 2019Article
- Homology Modeling-Based in Silico Affinity Maturation Improves the Affinity of a Nanobody.International journal of molecular sciences · 2019Article
- Enhancers Improve the AID-Induced Hypermutation in Episomal Vector for Antibody Affinity Maturation in Mammalian Cell Display.Antibodies (Basel, Switzerland) · 2018Article
- Article
- Tracing Antibody Repertoire Evolution by Systems Phylogeny.Frontiers in immunology · 2018Review
- Global mapping of antibody recognition of the hepatitis C virus E2 glycoprotein: Implications for vaccine design.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Alteration of Electrostatic Surface Potential Enhances Affinity and Tumor Killing Properties of Anti-ganglioside GD2 Monoclonal Antibody hu3F8.The Journal of biological chemistry · 2015Article
- Structural flexibility of a conserved antigenic region in hepatitis C virus glycoprotein E2 recognized by broadly neutralizing antibodies.Journal of virology · 2015Article
- Breadth of neutralization and synergy of clinically relevant human monoclonal antibodies against HCV genotypes 1a, 1b, 2a, 2b, 2c, and 3a.Hepatology (Baltimore, Md.) · 2014Article
- Reversion of somatic mutations of the respiratory syncytial virus-specific human monoclonal antibody Fab19 reveal a direct relationship between association rate and neutralizing potency.Journal of immunology (Baltimore, Md. : 1950) · 2013Article
- Cooperativity in virus neutralization by human monoclonal antibodies to two adjacent regions located at the amino terminus of hepatitis C virus E2 glycoprotein.Journal of virology · 2013Article
- Multiantibody strategies for HIV.Clinical & developmental immunology · 2013Review
- Neutralization interfering antibodies: a "novel" example of humoral immune dysfunction facilitating viral escape?Viruses · 2012Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
A potent neutralizing antibody to a conserved hepatitis C virus (HCV) epitope might overcome its extreme variability, allowing immunotherapy. The human monoclonal antibody HC-1 recognizes a conformational epitope on the HCV E2 glycoprotein. Previous studies showed that HC-1 neutralizes most HCV genotypes but has modest potency. To improve neutralization, we affinity-matured HC-1 by constructing a library of yeast-displayed HC-1 single chain Fv (scFv) mutants, using for selection an E2 antigen from one of the poorly neutralized HCVpp. We developed an approach by parallel mutagenesis of the heavy chain variable (VH) and κ-chain variable (Vk) genes separately, then combining the optimized VH and Vk mutants. This resulted in the generation of HC-1-related scFv variants exhibiting improved affinities. The best scFv variant had a 92-fold improved affinity. After conversion to IgG1, some of the antibodies exhibited a 30-fold improvement in neutralization activity. Both surface plasmon resonance and solution kinetic exclusion analysis showed that the increase in affinity was largely due to a lowering of the dissociation rate constant, Koff. Neutralization against a panel of HCV pseudoparticles and infectious 2a HCV virus improved with the affinity-matured IgG1 antibodies. Interestingly, some of these antibodies neutralized a viral isolate that was not neutralized by wild-type HC-1. Moreover, propagating 2a HCVcc under the selective pressure of WT HC-1 or affinity-matured HC-1 antibodies yielded no viral escape mutants and, with the affinity-matured IgG1, needed 100-fold less antibody to achieve complete virus elimination. Taken together, these findings suggest that affinity-matured HC-1 antibodies are excellent candidates for therapeutic development.
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.