Trial reportPloS one2014
High-throughput sequencing analysis of post-liver transplantation HCV E2 glycoprotein evolution in the presence and absence of neutralizing monoclonal antibody.
Trial report in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 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
19 citing papers in PubMed, 27 citations in OpenAlex.
- In Vivo Determinants of Hepatitis C Virus Adaptation and Escape From Neutralizing Antibody AR5A.Cellular and molecular gastroenterology and hepatology · 2026Article
- Hepatitis C Virus E1E2 Structure, Diversity, and Implications for Vaccine Development.Viruses · 2024Review
- Patient-derived monoclonal antibody neutralizes HCV infection in vitro and vivo without generating escape mutants.PloS one · 2022Article
- Review
- Review
- Mechanisms of Hepatitis C Virus Escape from Vaccine-Relevant Neutralizing Antibodies.Vaccines · 2021Review
- Structure-Based Design of Hepatitis C Virus E2 Glycoprotein Improves Serum Binding and Cross-Neutralization.Journal of virology · 2020Article
- Validation of Variant Assembly Using HAPHPIPE with Next-Generation Sequence Data from Viruses.Viruses · 2020Article
- An integrated software for virus community sequencing data analysis.BMC genomics · 2020Article
- Identifying immunologically-vulnerable regions of the HCV E2 glycoprotein and broadly neutralizing antibodies that target them.Nature communications · 2019Article
- Predicting the Effectiveness of Hepatitis C Virus Neutralizing Antibodies by Bioinformatic Analysis of Conserved Epitope Residues Using Public Sequence Data.Frontiers in immunology · 2018Article
- Computational Modeling of Hepatitis C Virus Envelope Glycoprotein Structure and Recognition.Frontiers in immunology · 2018Review
- Structure-Based Design of Hepatitis C Virus Vaccines That Elicit Neutralizing Antibody Responses to a Conserved Epitope.Journal of virology · 2017Article
- Limited naturally occurring escape in broadly neutralizing antibody epitopes in hepatitis C glycoprotein E2 and constrained sequence usage in acute infection.Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases · 2017Article
- Engineering Antibodies for the Treatment of Infectious Diseases.Advances in experimental medicine and biology · 2017Review
- Designing a B Cell-Based Vaccine against a Highly Variable Hepatitis C Virus.Frontiers in microbiology · 2017Review
- 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
- Viral evasion and challenges of hepatitis C virus vaccine development.Current opinion in virology · 2016Review
- Antibody-Based Strategies to Prevent and Treat Influenza.Frontiers in immunology · 2015Review
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 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chronic hepatitis C virus (HCV) infection is the most common cause of end-stage liver disease, often leading to liver transplantation, in which case circulating virions typically infect the transplanted liver within hours and viral concentrations can quickly exceed pre-transplant levels. MBL-HCV1 is a fully human monoclonal antibody recognizing a linear epitope of the HCV E2 envelope glycoprotein (amino acids 412-423). The ability of MBL-HCV1 to prevent HCV recurrence after liver transplantation was investigated in a phase 2 randomized clinical trial evaluating six MBL-HCV1-treated subjects and five placebo-treated subjects. MBL-HCV1 treatment significantly delayed time to viral rebound compared with placebo treatment. Here we report results from high-throughput sequencing on the serum of each of the eleven enrolled subjects prior to liver transplantation and after viral rebound. We further sequenced the sera of the MBL-HCV1-treated subjects at various interim time points to study the evolution of antibody-resistant viral variants. We detected mutations at one of two positions within the antibody epitope--mutations of N at position 415 to D, K or S, or mutation of N at position 417 to S. It has been previously reported that N415 is not glycosylated in the wild-type E2 protein, but N417S can lead to glycosylation at position 415. Thus N415 is a key position for antibody recognition and the only routes we identified for viral escape, within the constraints of HCV fitness in vivo, involve mutating or glycosylating this position. Evaluation of mutations along the entire E1 and E2 proteins revealed additional positions that changed moderately before and after MBL-HCV1 treatment for subsets of the six subjects, yet underscored the relative importance of position 415 in MBL-HCV1 resistance.
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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.