title: Type 1 interferon augments DNA-based vaccination against hepatitis C virus core protein.
abstract: Eradication of chronic hepatitis C virus (HCV) infection depends upon a broad-based cellular immune response. Genetic immunization stimulates such a response, but the resultant activity is generally weak. Type 1 interferons (IFNs), which are known for their direct anti-viral and anti-proliferative properties, possess vigorous immunomodulatory properties. The aim of this study was to assess the capacity of IFN-alpha to augment the cellular immune response to DNA vaccination against HCV core protein. Three types of IFN-alpha were investigated: the non-species-specific hybrid IFN A/D, human pegylated IFN-alpha, and a plasmid that expressed murine IFN-alpha. Low doses of hIFN-A/D and hPegIFN-alpha augmented three to fourfold the cellular immune response to DNA-based vaccination, determined in conventional CTL assays, as well as in an in vivo tumor challenge model. Importantly, augmentation occurred within a narrow concentration range; a further increase in IFN dosage suppressed the CTL response significantly. Humoral immunity showed a very similar pattern of augmentation. These findings demonstrate that the immunomodulatory properties of IFN-alpha can be exploited to augment DNA based immunization, but it is important to consider the effects of dose on both cellular and humoral immune response for optimal augmentation.
authors.affiliation: The Liver Research Center, Rhode Island Hospital and Brown Medical School, Providence, Rhode Island 02903, USA.
authors.forename: Stephan
authors.initials: S
authors.lastname: Gehring
authors.forename: Stephen H
authors.initials: SH
authors.lastname: Gregory
authors.forename: Noriyoshi
authors.initials: N
authors.lastname: Kuzushita
authors.forename: Jack R
authors.initials: JR
authors.lastname: Wands
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D005260:Female; D006526:Hepatitis C / Q000276:immunology*; D007370:Interferon Type I / Q000008:administration & dosage / Q000276:immunology*; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D011092:Polyethylene Glycols / Q000008:administration & dosage; D011994:Recombinant Proteins; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D013997:Time Factors; D019444:Vaccines, DNA / Q000276:immunology; D014758:Viral Core Proteins / Q000276:immunology*; D014761:Viral Hepatitis Vaccines / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D007370:Interferon Type I; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D019444:Vaccines, DNA; D014758:Viral Core Proteins; D014761:Viral Hepatitis Vaccines; D011092:Polyethylene Glycols; C100416:peginterferon alfa-2a