Anti‐hepatitis C virus activity of albinterferon alfa‐2b in cell culture

Abstract

Interferon-based combination therapy is the standard treatment for chronic hepatitis C virus (HCV) infection. The weekly administration of long-acting pegylated interferons (PEG-IFNalpha-2a or PEG-IFNalpha-2b) provides superior antiviral efficacy over standard interferon alfa (IFNalpha) for the treatment of HCV infection. Albinterferon alfa-2b (alb-IFN) is a novel recombinant protein consisting of IFNalpha-2b that is genetically fused to human albumin. To test alb-IFN antiviral efficacy, we compared the antiviral activity of unmodified IFNalpha with the three modified interferons (PEG-IFNalpha-2a, PEG-IFNalpha-2b, and alb-IFN) at clinically relevant serum concentrations using liver cell-based and non-liver cell-based HCV replicon cell lines. The EC(50) in GSB cells for IFNalpha-2b, PEG-IFNalpha-2a, PEG-IFNalpha-2b and alb-IFN was 7 U/mL, 1.1 ng/mL, 18 ng/mL, and 15 ng/mL, respectively. At clinically relevant patient serum concentrations, alb-IFN exhibits more antiviral activity than the pegylated interferons. Alb-IFN showed similar inhibition of HCV replication in human liver cells and non-liver cells, indicating it has anti-HCV activity in non-liver cells. The magnitude of induction of interferon-stimulated genes (MxA, 2'5'OAS1, IFI44, and IFI27) at 6 h and 48 h was comparable for all the modified IFNs in human liver cells at the drug concentrations evaluated. The present study indicates that alb-IFN has a potent, direct anti-HCV activity in both liver and non-liver cells.