Prevention of hepatitis C virus infection using a broad cross-neutralizing monoclonal antibody (AR4A) and epigallocatechin gallate

Liver Transpl. 2016 Mar;22(3):324-32. doi: 10.1002/lt.24344. Epub 2016 Jan 29.

Abstract

The anti-hepatitis C virus (HCV) activity of a novel monoclonal antibody (mAb; AR4A) and epigallocatechin gallate (EGCG) were studied in vitro using a HCV cell culture system and in vivo using a humanized liver mouse model capable of supporting HCV replication. Alone, both exhibit reliable cross-genotype HCV inhibition in vitro, and combination therapy completely prevented HCV infection. In vitro AR4A mAb (alone and combined with EGCG) robustly protects against the establishment of HCV genotype 1a infection. EGCG alone fails to reliably protect against an HCV challenge. In conclusion, AR4A mAb represents a safe and efficacious broadly neutralizing antibody against HCV applicable to strategies to safely prevent HCV reinfection following liver transplantation, and it lends further support to the concept of HCV vaccine development. The poor bioavailability of EGCG limits HCV antiviral activity in vitro.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / pharmacology*
  • Antibodies, Neutralizing / pharmacology*
  • Antiviral Agents / pharmacology*
  • Broadly Neutralizing Antibodies
  • Catechin / analogs & derivatives*
  • Catechin / pharmacology
  • Cell Line
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Drug Therapy, Combination
  • Genotype
  • Hepatitis C / diagnosis
  • Hepatitis C / immunology
  • Hepatitis C / prevention & control*
  • Hepatitis Viruses / drug effects*
  • Hepatitis Viruses / genetics
  • Hepatitis Viruses / immunology
  • Humans
  • Liver / drug effects*
  • Liver / immunology
  • Liver / virology
  • Mice, SCID
  • Time Factors

Substances

  • AR4A cross-neutralizing monoclonal antibody
  • Antibodies, Monoclonal
  • Antibodies, Neutralizing
  • Antiviral Agents
  • Broadly Neutralizing Antibodies
  • Catechin
  • epigallocatechin gallate