Enhancing B- and T-cell immune response to a hepatitis C virus E2 DNA vaccine by intramuscular electrical gene transfer.
We describe an improved genetic immunization strategy for eliciting a full spectrum of anti-hepatitis C virus (HCV) envelope 2 (E2) glycoprotein responses in mammals through electrical gene transfer (EGT) of plasmid DNA into muscle fibers. Intramuscular injection of a plasmid encoding a cross-reactive hypervariable region 1 (HVR1) peptide mimic fused at the N terminus of the E2 ectodomain, followed by electrical stimulation treatment in the form of high-frequency, low-voltage electric pulses, induced more than 10-fold-higher expression levels in the transfected mouse tissue. As a result of this substantial increment of in vivo antigen production, the humoral response induced in mice, rats, and rabbits ranged from 10- to 30-fold higher than that induced by conventional naked DNA immunization. Consequently, immune sera from EGT-treated mice displayed a broader cross-reactivity against HVR1 variants from natural isolates than sera from injected animals that were not subjected to electrical stimulation. Cellular response against E2 epitopes specific for helper and cytotoxic T cells was significantly improved by EGT. The EGT-mediated enhancement of humoral and cellular immunity is antigen independent, since comparable increases in antibody response against ciliary neurotrophic factor or in specific anti-human immunodeficiency virus type 1 gag CD8(+) T cells were obtained in rats and mice. Thus, the method described potentially provides a safe, low-cost treatment that may be scaled up to humans and may hold the key for future development of prophylactic or therapeutic vaccines against HCV and other infectious diseases.
Zucchelli
S
S
Istituto di Ricerche di Biologia Molecolare P. Angeletti, 00040 Pomezia (Rome), Italy.
Capone
S
S
Fattori
E
E
Folgori
A
A
Di Marco
A
A
Casimiro
D
D
Simon
A J
AJ
Laufer
R
R
La Monica
N
N
Cortese
R
R
Nicosia
A
A
D017502:Adenovirus E2 Proteins / Q000235:genetics / Q000276:immunology*; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000821:virology; D004279:DNA, Viral / Q000235:genetics / Q000276:immunology*; D018274:Electroporation; D016174:Hepacivirus / Q000276:immunology*; D006526:Hepatitis C / Q000276:immunology* / Q000517:prevention & control; D007109:Immunity; D051379:Mice; D011817:Rabbits; D051381:Rats; D013601:T-Lymphocytes / Q000276:immunology / Q000821:virology; D014162:Transfection; D019444:Vaccines, DNA / Q000276:immunology; D014761:Viral Hepatitis Vaccines / Q000276:immunology*
D017502:Adenovirus E2 Proteins; D004279:DNA, Viral; D019444:Vaccines, DNA; D014761:Viral Hepatitis Vaccines