DNA-based immunization breaks tolerance in a hepatitis C virus transgenic mouse model.
Chronic hepatitis C infection (HCV) is associated with high morbidity and mortality due to limited treatment options. HCV transgenic mice can be used as surrogate model of chronic HCV infection and may therefore be a small animal model for the evaluation of therapeutic vaccination strategies. We immunized transgenic mice expressing HCV structural proteins with an HCV core and a mouse IL-2 expression plasmid to study the cellular and humoral immune responses. DNA-based immunization induced a significant CD4+ T cell proliferative response and a CD8+ cytotoxic T cell response. Only low amounts of anti-HCV core antibodies were detected after genetic immunization. No liver damage was observed in the liver of immunized mice despite low level HCV core transgene expression and the presence of peripheral cellular immunity. These results demonstrate that DNA-based immunization may result in activation of previously tolerant T cells and is therefore a promising approach for treatment of chronic HCV infection.
Encke
Jens
J
Molecular Hepatology Laboratory, Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, Massachusetts, USA. Jens_Encke@med.uni-heidelberg.de
Geissler
Michael
M
Stremmel
Wolfgang
W
Wands
Jack R
JR
D000818:Animals; D000917:Antibody Formation / Q000235:genetics / Q000276:immunology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D016207:Cytokines / Q000378:metabolism; D004279:DNA, Viral / Q000276:immunology; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics* / Q000276:immunology*; D006526:Hepatitis C / Q000276:immunology* / Q000517:prevention & control*; D018936:Hepatitis C Antigens / Q000276:immunology*; D007108:Immune Tolerance / Q000235:genetics* / Q000276:immunology*; D007376:Interleukin-2 / Q000096:biosynthesis; D008099:Liver / Q000378:metabolism; D018655:Lymphocyte Count; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D010957:Plasmids / Q000276:immunology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D019444:Vaccines, DNA / Q000276:immunology; D014761:Viral Hepatitis Vaccines / Q000276:immunology*
D016207:Cytokines; D004279:DNA, Viral; D018936:Hepatitis C Antigens; D007376:Interleukin-2; D012333:RNA, Messenger; D019444:Vaccines, DNA; D014761:Viral Hepatitis Vaccines