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In the present study, we showed that gene electrotransfer (GET) of a novel candidate DNA vaccine encoding an optimized version of the nonstructural region of HCV (from NS3 to NS5B) induced substantially more potent, broad, and long-lasting CD4+ and CD8+ cellular immunity than naked DNA injection in mice and in rhesus macaques as measured by a combination of assays, including IFN-\u03b3 ELISPOT, intracellular cytokine staining, and cytotoxic T cell assays. A protocol based on three injections of DNA with GET induced a substantially higher CD4+ T cell response than an adenovirus 6-based viral vector encoding the same Ag. To better evaluate the immunological potency and probability of success of this vaccine, we have immunized two chimpanzees and have compared vaccine-induced cell-mediated immunity to that measured in acute self-limiting infection in humans. GET of the candidate HCV vaccine led to vigorous, multispecific IFN-\u03b3+CD8+ and CD4+ T lymphocyte responses in chimpanzees, which were comparable to those measured in five individuals that cleared spontaneously HCV infection. These data support the hypothesis that T cell responses elicited by the present strategy could be beneficial in prophylactic vaccine approaches against HCV.<\/jats:p>","DOI":"10.4049\/jimmunol.177.10.7462","type":"journal-article","created":{"date-parts":[[2014,4,18]],"date-time":"2014-04-18T19:39:04Z","timestamp":1397849944000},"page":"7462-7471","source":"Crossref","is-referenced-by-count":74,"title":["Modulation of the Immune Response Induced by Gene Electrotransfer of a Hepatitis C Virus DNA Vaccine in Nonhuman Primates"],"prefix":"10.1093","volume":"177","author":[{"given":"Stefania","family":"Capone","sequence":"first","affiliation":[{"name":"Istituto di Ricerche di Biologia Molecolare , \u201cP. 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