ArticleHepatology (Baltimore, Md.)2016
Monoclonal anti-envelope antibody AP33 protects humanized mice against a patient-derived hepatitis C virus challenge.
Article in Hepatology (Baltimore, Md.), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 38 citations in OpenAlex.
- In Vivo Determinants of Hepatitis C Virus Adaptation and Escape From Neutralizing Antibody AR5A.Cellular and molecular gastroenterology and hepatology · 2026Article
- The red algaProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Current Hepatitis C Vaccine Candidates Based on the Induction of Neutralizing Antibodies.Viruses · 2023Review
- Production and immunogenicity of different prophylactic vaccines for hepatitis C virus (Review).Experimental and therapeutic medicine · 2022Review
- Recombinant Full-Length Hepatitis C Virus E1E2 Dimer Elicits Pangenotypic Neutralizing Antibodies.Frontiers in immunology · 2022Article
- Hepatitis C virus E2 envelope glycoprotein produced in Nicotiana benthamiana triggers humoral response with virus-neutralizing activity in vaccinated mice.Plant biotechnology journal · 2021Article
- Antibody Responses in Hepatitis C Infection.Cold Spring Harbor perspectives in medicine · 2021Review
- Development of a structural epitope mimic: an idiotypic approach to HCV vaccine design.NPJ vaccines · 2021Article
- A Role for B Cells to Transmit Hepatitis C Virus Infection.Frontiers in immunology · 2021Observational
- Global and local envelope protein dynamics of hepatitis C virus determine broad antibody sensitivity.Science advances · 2020Article
- In vivo combination of human anti-envelope glycoprotein E2 and -Claudin-1 monoclonal antibodies for prevention of hepatitis C virus infection.Antiviral research · 2019Article
- Mouse Models for Studying HCV Vaccines and Therapeutic Antibodies.Methods in molecular biology (Clifton, N.J.) · 2019Article
- Immunogenetic and structural analysis of a class of HCV broadly neutralizing antibodies and their precursors.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Article
- The Neutralizing Face of Hepatitis C Virus E2 Envelope Glycoprotein.Frontiers in immunology · 2018Review
- Conformational Flexibility in the CD81-Binding Site of the Hepatitis C Virus Glycoprotein E2.Frontiers in immunology · 2018Review
- A novel neutralizing human monoclonal antibody broadly abrogates hepatitis C virus infection in vitro and in vivo.Antiviral research · 2017Article
- Immunization With a Subunit Hepatitis C Virus Vaccine Elicits Pan-Genotypic Neutralizing Antibodies and Intrahepatic T-Cell Responses in Nonhuman Primates.The Journal of infectious diseases · 2017Article
- Altered Glycosylation Patterns Increase Immunogenicity of a Subunit Hepatitis C Virus Vaccine, Inducing Neutralizing Antibodies Which Confer Protection in Mice.Journal of virology · 2016Article
- Identification of a New Benzimidazole Derivative as an Antiviral against Hepatitis C Virus.Journal of virology · 2016Article
Corrections and comments
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Authors and funding
13 authors at 7 institutions in 3 countries.
Funding
Abstract
unlabelledEnd-stage liver disease (ESLD) caused by hepatitis C virus (HCV) infection is a major indication for liver transplantation. However, immediately after transplantation, the liver graft of viremic patients universally becomes infected by circulating virus, resulting in accelerated liver disease progression. Currently available direct-acting antiviral therapies have reduced efficacy in patients with ESLD and prophylactic strategies to prevent HCV recurrence are still highly needed. In this study, we compared the ability of two broadly reactive monoclonal antibodies (mAbs), designated 3/11 and AP33, recognizing a distinct, but overlapping, epitope in the viral E2 glycoprotein to protect humanized mice from a patient-derived HCV challenge. Their neutralizing activity was assessed using the HCV pseudoparticles and cell-culture-derived HCV systems expressing multiple patient-derived envelopes and a human-liver chimeric mouse model. HCV RNA was readily detected in all control mice challenged with a patient-derived HCV genotype 1b isolate, whereas 3 of 4 AP33-treated mice were completely protected. In contrast, only one of four 3/11-treated mice remained HCV-RNA negative throughout the observation period, whereas the other 3 had a viral load that was indistinguishable from that in the control group. The increased in vivo efficacy of AP33 was in line with its higher affinity and neutralizing capacity observed in vitro.
conclusionsAlthough mAbs AP33 and 3/11 target the same region in E2, only mAb AP33 can efficiently protect from challenge with a heterologous HCV population in vivo. Given that mAb AP33 efficiently neutralizes viral variants that escaped the humoral immune response and reinfected the liver graft of transplant patients, it may be a valuable candidate to prevent HCV recurrence. In addition, our data are valuable for the design of a prophylactic vaccine.
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