Strong HCV NS3- and NS4A-specific cellular immune responses induced in mice and Rhesus macaques by a novel HCV genotype 1a/1b consensus DNA vaccine

Vaccine. 2008 Nov 18;26(49):6225-31. doi: 10.1016/j.vaccine.2008.07.052. Epub 2008 Aug 8.

Abstract

Hepatitis C virus (HCV) represents a major health burden with more than 170 million individuals currently infected worldwide, equaling roughly 3% of the world's population. HCV preferentially infects hepatocytes and is able to persist in up to 70% of infected individuals. It is estimated that up to 30% of chronically infected individuals will go on to develop progressive liver disease as a result of HCV infection, making the virus the leading cause of liver transplantation in the world. Currently there is no vaccine for HCV. In this study, we have taken a multi-step approach to develop a novel genotype 1a/1b consensus HCV NS3/NS4A DNA vaccine able to induce strong cellular immunity. We show that this construct is able to induce strong anti-NS3/NS4A T cell responses in C57BL/6 mice, as well as, in Rhesus macaques. Our data suggest that DNA vaccines encoding HCV proteins NS3/NS4A merit further study in the context of future prophylactic and therapeutic HCV T cell based vaccines.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Carrier Proteins / immunology*
  • Cell Separation
  • Electroporation
  • Enzyme-Linked Immunosorbent Assay
  • Epitope Mapping
  • Fluorescent Antibody Technique
  • Genotype
  • Hepacivirus / genetics*
  • Hepacivirus / immunology*
  • Immunity, Cellular / immunology*
  • Immunization
  • Interferon-gamma / biosynthesis
  • Interferon-gamma / genetics
  • Intracellular Signaling Peptides and Proteins
  • Macaca mulatta
  • Mice
  • Mice, Inbred C57BL
  • Molecular Sequence Data
  • Spleen / cytology
  • Vaccines, DNA / immunology
  • Viral Nonstructural Proteins / immunology*
  • Viral Proteins / immunology*

Substances

  • Carrier Proteins
  • Intracellular Signaling Peptides and Proteins
  • NS3 protein, hepatitis C virus
  • NS4A cofactor peptide, Hepatitis C virus
  • Vaccines, DNA
  • Viral Nonstructural Proteins
  • Viral Proteins
  • Interferon-gamma