Cellular immunogenicity of a multi-epitope peptide vaccine candidate based on hepatitis C virus NS5A, NS4B and core proteins in HHD-2 mice

J Virol Methods. 2013 Apr;189(1):47-52. doi: 10.1016/j.jviromet.2013.01.003. Epub 2013 Jan 16.

Abstract

To develop a vaccine against hepatitis C virus (HCV), a multi-epitope peptide was synthesized from nonstructural proteins containing HLA-A2 epitopes inducing mainly responses in natural infection. The engineered vaccine candidate, VAL-44, consists of multiple epitopes from the HCV NS5A, NS4B and core proteins. Immunization with the VAL-44 peptide induced higher CTL responses than those by the smaller VL-20 peptide. VAL-44 induced antigen-specific IFN-γ-producing CD4+ T cells and CD8+ T cells. VAL-44 elicited a Th1-biased immune response with secretion of high amounts of IFN-γ and IL-2, compared with VL-20. These results suggest that VAL-44 can elicit strong cellular immune responses. The VAL-44 peptide stimulated IFN-γ production from viral-specific peripheral blood mononuclear cells (PBMCs) of patients infected with HCV. These results suggest that VAL-44 could be developed as a potential HCV multi-epitope peptide vaccine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Amino Acid Sequence
  • Animals
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Cell Line
  • Cell Proliferation
  • Epitopes, T-Lymphocyte / immunology*
  • Female
  • Hepacivirus / immunology*
  • Humans
  • Immunization
  • Interferon-gamma / metabolism
  • Interleukin-2 / metabolism
  • Leukocytes, Mononuclear / immunology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Middle Aged
  • T-Lymphocytes / immunology
  • Vaccines, Subunit / immunology
  • Vaccines, Synthetic
  • Viral Hepatitis Vaccines / immunology*
  • Viral Nonstructural Proteins / immunology*
  • Young Adult

Substances

  • Epitopes, T-Lymphocyte
  • Interleukin-2
  • NS4B protein, flavivirus
  • Vaccines, Subunit
  • Vaccines, Synthetic
  • Viral Hepatitis Vaccines
  • Viral Nonstructural Proteins
  • Interferon-gamma
  • NS-5 protein, hepatitis C virus