title: Effective induction of type 1 cytotoxic T cell responses in mice with DNA vaccine encoding two hepatitis C virus cytotoxic T lymphocyte epitopes.
abstract: The aims of this study were to explain whether a multiple cytotoxic T lymphocyte (CTL) epitope-based anti-hepatitis C virus (HCV) DNA vaccine can induce specific CTL responses to each HCV CTL epitope independently and long-term CD8(+) T cell memory responses, and to determine the cytokine secretion pattern and subtype of epitope-specific cytotoxic T cells. A multi-CTL epitope gene, which consists of two epitopes of HCV (H-2(d)-restricted HCV core(133142) and E1(315322)), was cloned into the eukaryotic expression vector pcDNA3.1. BALB/c mice (H-2(d) restricted) were vaccinated intramuscularly with this multi-CTL epitope-based DNA vaccine. The epitope-specific CTLs against target cells (P815,H-2(d) restricted) pulsed with various CTL epitope peptides were detected by lactate dehydrogenase release assay, and the precursor frequency of epitope-specific CTLs was determined by limiting dilution analysis. Cytokines (interleukin [IL]-2, IL-4, and interferon-) in culture supernatants were determined by enzyme-linked immunosorbent assay. The multi-CTL epitope-based DNA vaccine directed against two HCV CTL epitopes could induce specific CTL responses to each of the two CTL epitopes independently and long-term CD8(+) T cell memory responses. The epitope-specific cytotoxic T cells produced helper T cell type 1 cytokines. This work demonstrated that multiepitope DNA vaccination is a potential strategy to control HCV infection.
authors.affiliation: Department of Immunology and Microbiology, Xi'an Jiaotong University School of Medicine, Xi'an, PR China.
authors.forename: Lin
authors.initials: L
authors.lastname: Shi
authors.forename: Shan
authors.initials: S
authors.lastname: Liu
authors.forename: Gui-Xiang
authors.initials: GX
authors.lastname: Fan
authors.forename: Li
authors.initials: L
authors.lastname: Sheng
authors.forename: Hui-Xun
authors.initials: HX
authors.lastname: Ren
authors.forename: Yu-Kang
authors.initials: YK
authors.lastname: Yuan
mesh_terms: D000818:Animals; D004797:Enzyme-Linked Immunosorbent Assay; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D005822:Genetic Vectors; D006183:H-2 Antigens; D016174:Hepacivirus / Q000276:immunology*; D006526:Hepatitis C / Q000276:immunology*; D007156:Immunologic Memory; D007273:Injections, Intramuscular; D007372:Interferons / Q000032:analysis / Q000096:biosynthesis; D007376:Interleukin-2 / Q000032:analysis / Q000096:biosynthesis; D015847:Interleukin-4 / Q000032:analysis / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C / Q000276:immunology; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000276:immunology; D013045:Species Specificity; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology; D014758:Viral Core Proteins / Q000235:genetics / Q000276:immunology; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology; D014761:Viral Hepatitis Vaccines / Q000008:administration & dosage / Q000276:immunology*
chemical_list: C087035:E1 protein, Hepatitis C virus; D018984:Epitopes, T-Lymphocyte; D006183:H-2 Antigens; D007376:Interleukin-2; D011994:Recombinant Proteins; D019444:Vaccines, DNA; D014758:Viral Core Proteins; D014759:Viral Envelope Proteins; D014761:Viral Hepatitis Vaccines; C069130:nucleocapsid protein, Hepatitis C virus; D015847:Interleukin-4; D007372:Interferons