Immunogenicity of an influenza virus-vectored vaccine carrying the hepatitis C virus protein epitopes in mice

Antiviral Res. 2017 Sep:145:168-174. doi: 10.1016/j.antiviral.2017.07.015. Epub 2017 Aug 1.

Abstract

Hepatitis C virus (HCV) has a devastating impact on human health, and infections can progress into liver fibrosis, cirrhosis, and hepatocellular carcinoma. There is no effective HCV vaccine. In this study, we rescued a recombinant PR8 influenza viral vector, called rgFLU-HCVCE1E2, carrying the core and envelope glycoprotein (C/E1/E2) epitopes of HCV inserted into the influenza nonstructural protein 1 gene. The morphological characteristics of rgFLU-HCVCE1E2 and the expression of the C/E1/E2 epitopes of HCV were examined. rgFLU-HCVCE1E2 replicated in various cell lines, including MDCK, A549, and Huh7.5 cells. More importantly, in BALB/c mice immunized intranasally twice at a 21-day interval with 104, 105, or 106 TCID50 rgFLU-HCVCE1E2, the viral vector induced a robust antibody response to influenza and HCV and potent IFN-γ and IL-4 secretion in response to HCV antigens in a dose-dependent manner. The rgFLU-HCVCE1E2 virus also stimulated IFN-γ production by virus-specific peripheral blood mononuclear cells in patients with chronic HCV infection. The study demonstrated that rgFLU-HCVCE1E2 carrying HCV antigens is immunogenic in vivo and has potential for the development of a HCV vaccine.

Keywords: HCV epitopes; Influenza virus vector.

MeSH terms

  • A549 Cells
  • Administration, Intranasal
  • Animals
  • Antibodies, Viral / biosynthesis
  • Antibodies, Viral / blood
  • Antibodies, Viral / immunology
  • Dogs
  • Epitopes / immunology*
  • Genetic Vectors
  • Hepacivirus / genetics
  • Hepacivirus / immunology*
  • Humans
  • Immunization
  • Immunogenicity, Vaccine*
  • Interferon-gamma / immunology
  • Interferon-gamma / metabolism
  • Interleukin-4 / immunology
  • Interleukin-4 / metabolism
  • Madin Darby Canine Kidney Cells
  • Mice
  • Mice, Inbred BALB C
  • Vaccines, Synthetic / immunology
  • Viral Envelope Proteins / genetics
  • Viral Envelope Proteins / immunology
  • Viral Envelope Proteins / metabolism
  • Viral Hepatitis Vaccines / administration & dosage
  • Viral Hepatitis Vaccines / chemistry
  • Viral Hepatitis Vaccines / genetics
  • Viral Hepatitis Vaccines / immunology*

Substances

  • Antibodies, Viral
  • Epitopes
  • Vaccines, Synthetic
  • Viral Envelope Proteins
  • Viral Hepatitis Vaccines
  • Interleukin-4
  • Interferon-gamma