Effective induction of type 1 cytotoxic T cell responses in mice with DNA vaccine encoding two hepatitis C virus cytotoxic T lymphocyte epitopes.
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.
Shi
Lin
L
Department of Immunology and Microbiology, Xi'an Jiaotong University School of Medicine, Xi'an, PR China.
Liu
Shan
S
Fan
Gui-Xiang
GX
Sheng
Li
L
Ren
Hui-Xun
HX
Yuan
Yu-Kang
YK
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*
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