Format

Send to

Choose Destination
Hepatology. 2016 Apr;63(4):1120-34. doi: 10.1002/hep.28428. Epub 2016 Feb 22.

Monoclonal anti-envelope antibody AP33 protects humanized mice against a patient-derived hepatitis C virus challenge.

Author information

1
Center for Vaccinology, Ghent University, Ghent, Belgium.
2
Inserm U1110, Institut de Recherche sur les Maladies Virales et Hépatiques, Strasbourg, France.
3
Université de Strasbourg, Strasbourg, France.
4
Laboratoire de Virologie, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.
5
Institut Hopitalo-Universitaire, Pole Hépato-digestif, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.
6
MRC-University of Glasgow Center for Virus Research, University of Glasgow, Glasgow, United Kingdom.
7
Viral Hepatitis Research Group, Center for Human Virology, University of Birmingham, Birmingham, United Kingdom.

Abstract

End-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.

CONCLUSIONS:

Although 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.

PMID:
26710081
DOI:
10.1002/hep.28428
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center