Modulation of the immune response induced by gene electrotransfer of a hepatitis C virus DNA vaccine in nonhuman primates

Stefania Capone, Immacolata Zampaglione, Alessandra Vitelli, Monica Pezzanera, Lisa Kierstead, Janine Burns, Lionello Ruggeri, Mirko Arcuri, Manuela Cappelletti, Annalisa Meola, Bruno Bruni Ercole, Rosalba Tafi, Claudia Santini, Alessandra Luzzago, Tong Ming Fu, Stefano Celloca, Gennaro Ciliberto, Riccardo Cortese, Alfredo Nicosia, Elena FattoriAntonella Folgori

Research output: Contribution to journalArticle

Abstract

Induction of multispecific, functional CD4+ and CD8+ T cells is the immunological hallmark of acute self-limiting hepatitis C virus (HCV) infection in humans. 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-γ 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-γ+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.

Original languageEnglish
Pages (from-to)7462-7471
Number of pages10
JournalJournal of Immunology
Volume177
Issue number10
Publication statusPublished - Nov 15 2006

ASJC Scopus subject areas

  • Immunology

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    Capone, S., Zampaglione, I., Vitelli, A., Pezzanera, M., Kierstead, L., Burns, J., Ruggeri, L., Arcuri, M., Cappelletti, M., Meola, A., Ercole, B. B., Tafi, R., Santini, C., Luzzago, A., Fu, T. M., Celloca, S., Ciliberto, G., Cortese, R., Nicosia, A., ... Folgori, A. (2006). Modulation of the immune response induced by gene electrotransfer of a hepatitis C virus DNA vaccine in nonhuman primates. Journal of Immunology, 177(10), 7462-7471.