Monoclonal anti-envelope antibody AP33 protects humanized mice against a patient-derived hepatitis C virus challenge.
Fiche publication
Date publication
avril 2016
Journal
Hepatology (Baltimore, Md.)
Auteurs
Membres identifiés du Cancéropôle Est :
Pr BAUMERT Thomas, Pr PESSAUX Patrick
Tous les auteurs :
Desombere I, Fafi-Kremer S, Van Houtte F, Pessaux P, Farhoudi A, Heydmann L, Verhoye L, Cole S, McKeating JA, Leroux-Roels G, Baumert TF, Patel AH, Meuleman P
Lien Pubmed
Résumé
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.
Mots clés
Animals, Antibodies, Monoclonal, pharmacology, Cells, Cultured, Disease Models, Animal, Enzyme-Linked Immunosorbent Assay, Epitopes, Hepacivirus, immunology, Hepatitis C, drug therapy, Hepatitis C Antibodies, immunology, Humans, Mice, Mice, Transgenic, Statistics, Nonparametric, Viral Envelope Proteins, immunology
Référence
Hepatology. 2016 Apr;63(4):1120-34