The development of a modified human IFN-alpha2b linked to the Fc portion of human IgG1 as a novel potential therapeutic for the treatment of hepatitis C virus infection

J Interferon Cytokine Res. 2004 Sep;24(9):560-72. doi: 10.1089/jir.2004.24.560.


Interferon-alpha (IFN-alpha), in conjunction with ribavirin, is the current standard for the treatment of chronic hepatitis C virus (HCV) infection. This treatment requires frequent dosing, with a significant risk of the development of anti-IFN-alpha neutralizing antibodies that correlates with lack of efficacy or relapse. We have developed an IFN-alpha linked to the Fc region of human IgG1 for improved half-life and less frequent dosing. We have also identified, using a human T cell proliferation assay, three regions of IFN-alpha2b that are potentially immunogenic, and a variant containing a total of six mutations within these regions was made. This variant was made as a fusion to Fc either with or without a flexible linker between the fusion partners. Both configurations of the variant were less active than native IFN-alpha alone, although the variant containing the flexible linker had in vitro antiviral activity within the range of other modified IFN-alphas currently in clinical use. Peptides spanning the modified regions were tested in T cell proliferation assays and found to be less immunogenic than native controls when using peripheral blood mononuclear cells (PBMCs) from both healthy individuals and HCV-infected patients who had been treated previously with IFN-alpha2b.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Antiviral Agents / chemistry*
  • Antiviral Agents / therapeutic use
  • Cell Line
  • Epitopes, T-Lymphocyte / analysis
  • Hepacivirus / drug effects
  • Hepacivirus / immunology
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / immunology
  • Humans
  • Immunoglobulin Fc Fragments / genetics*
  • Immunoglobulin Fc Fragments / immunology
  • Immunoglobulin Fc Fragments / metabolism
  • Immunoglobulin Fragments / immunology
  • Immunoglobulin G / genetics*
  • Immunoglobulin G / immunology
  • Interferon alpha-2
  • Interferon-alpha / chemistry
  • Interferon-alpha / genetics*
  • Interferon-alpha / therapeutic use
  • Molecular Sequence Data
  • Peptides / genetics
  • Point Mutation
  • Recombinant Fusion Proteins / immunology
  • Recombinant Proteins


  • Antiviral Agents
  • Epitopes, T-Lymphocyte
  • Immunoglobulin Fc Fragments
  • Immunoglobulin Fragments
  • Immunoglobulin G
  • Interferon alpha-2
  • Interferon-alpha
  • Peptides
  • Recombinant Fusion Proteins
  • Recombinant Proteins