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 respo nses in mammals through electrical gene transfer (EGT) of plasmid DNA into muscle fibers. Intramuscular injection of a plasmid encoding a cross-reacti ve hypervariable region 1 (HVR1) peptide mimic fused at the N terminus of t he E2 ectodomain, followed by electrical stimulation treatment in the form of high-frequency, low-voltage electric pulses, induced more than 10-fold-h igher expression levels in the transfected mouse tissue. As a result of thi s 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 s era from EGT-treated mice displayed a broader cross-reactivity against HVR1 variants from natural isolates than sera from injected animals that were n ot subjected to electrical stimulation. Cellular response against E2 epitop es specific for helper and cytotoxic T cells was significantly improved by EGT. The EGT-mediated enhancement of Immoral and cellular immunity is antig en independent, since comparable increases in antibody response against cil iary neurotrophic factor or in specific anti-human immunodeficiency virus t ype 1 gag CD8(+) T cells were obtained in rats and mice. Thus, the method d escribed potentially provides a safe, low-cost treatment that may be scaled up to humans and may hold the key for future development of prophylactic o r therapeutic vaccines against HCV and other infectious diseases.