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Journal of Virology, December 2000, p. 11598-11607, Vol. 74, No. 24
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Enhancing B- and T-Cell Immune Response to a Hepatitis C Virus E2 DNA Vaccine by Intramuscular Electrical Gene Transfer

Silvia Zucchelli,1 Stefania Capone,1 Elena Fattori,1 Antonella Folgori,1 Annalise Di Marco,1 Danilo Casimiro,2 Adam J. Simon,2 Ralph Laufer,1 Nicola La Monica,1 Riccardo Cortese,1 and Alfredo Nicosia1,*

Istituto di Ricerche di Biologia Molecolare P. Angeletti, 00040 Pomezia (Rome), Italy,1 and Department of Virus and Cell Biology, Merck Research Laboratories, West Point, Pennsylvania 194862

Received 8 May 2000/Accepted 18 September 2000

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.

* Corresponding author. Mailing address: Istituto di Ricerche di Biologia Moleculare P. Angeletti, Via Pontina Km 30-600, 00040 Pomezia (Rome), Italy. Phone: 3906-91093290. Fax: 3906-91093654. E-mail: alfredo_nicosia{at}merck.com.

Journal of Virology, December 2000, p. 11598-11607, Vol. 74, No. 24
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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