DNA-based vaccination against hepatitis C virus (HCV): effect of expressing different forms of HCV E2 protein and use of CpG-optimized vectors in mice.
DNA-based immunization may be of prophylactic and therapeutic value for hepatitis C virus (HCV) infection. In efforts to improve the immunogenicity of a plasmid expressing the second envelope protein (E2) of HCV, we evaluated in mice the role of the antigen localization and demonstrated that membrane-bound and secreted forms induced higher titers of E2-specific antibodies, as well as earlier and higher seroconversion rates, than the intracellular form, but all three forms induced strong CTL. We also investigated whether E2-specific antibody responses could be enhanced by CpG optimization of the plasmid backbone and showed that removal of neutralizing CpG dinucleotides did not have a significant effect but addition of 64 immunostimulatory CpG motifs significantly enhanced anti-E2 titers. These results may have implications for the design and development of HCV DNA vaccines.
Ma
Xiaoying
X
Loeb Health Research Institute, 725 Parkdale Avenue, Ottawa, Ont., Canada K1Y 4E9.
Forns
Xavier
X
Gutierrez
Robin
R
Mushahwar
Isa K
IK
Wu
Tong
T
Payette
Paul J
PJ
Bukh
Jens
J
Purcell
Robert H
RH
Davis
Heather L
HL
D000818:Animals; D001483:Base Sequence; D018899:CpG Islands; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D005822:Genetic Vectors; D016174:Hepacivirus / Q000235:genetics* / Q000276:immunology*; D006526:Hepatitis C / Q000276:immunology / Q000517:prevention & control; D018937:Hepatitis C Antibodies / Q000096:biosynthesis; D018936:Hepatitis C Antigens / Q000235:genetics; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D019444:Vaccines, DNA / Q000235:genetics; D014759:Viral Envelope Proteins / Q000235:genetics* / Q000276:immunology*; D014761:Viral Hepatitis Vaccines / Q000235:genetics*
D004279:DNA, Viral; D018937:Hepatitis C Antibodies; D018936:Hepatitis C Antigens; D019444:Vaccines, DNA; D014759:Viral Envelope Proteins; D014761:Viral Hepatitis Vaccines; C091015:glycoprotein E2, Hepatitis C virus