Modulation of the immune response induced by gene electrotransfer of a hepatitis C virus DNA vaccine in nonhuman primates
| Autor: | Antonella Folgori, Manuela Cappelletti, Janine A. Burns, Immacolata Zampaglione, Gennaro Ciliberto, Alessandra Luzzago, Alessandra Vitelli, Stefania Capone, Rosalba Tafi, Annalisa Meola, Monica Pezzanera, Alfredo Nicosia, Lionello Ruggeri, Riccardo Cortese, Lisa Kierstead, Stefano Colloca, Elena Fattori, Tong-Ming Fu, Mirko Arcuri, Claudia Santini, Bruno Bruni Ercole |
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| Přispěvatelé: | S., Capone, I., Zampaglione, A., Vitelli, M., Pezzanera, L., Kierstead, J., Burn, L., Ruggeri, M., Arcuri, M., Cappelletti, A., Meola, B. B., Ercole, R., Tafi, C., Santini, A., Luzzago, T. M., Fu, S., Colloca, G., Ciliberto, R., Cortese, Nicosia, Alfredo, E., Fattori, A., Folgori |
| Předmět: |
CD4-Positive T-Lymphocytes
Cellular immunity Pan troglodytes CD8-T-CELL MEMORY T cell Immunology LARGE ANIMALS Hepacivirus CD8-Positive T-Lymphocytes Viral Nonstructural Proteins Biology Cell Line Viral vector DNA vaccination Mice Immune system IMMUNODEFICIENCY-VIRUS Vaccines DNA medicine Animals Humans Immunology and Allergy Cytotoxic T cell CD4-T-CELL HELP Codon CELL RESPONSE T-LYMPHOCYTE RESPONSES Immunity Cellular Mice Inbred BALB C ELISPOT Gene Transfer Techniques Macaca mulatta Virology Electroporation medicine.anatomical_structure Naked DNA RHESUS MACAQUES HCV ACUTE INFECTION Female ELECTROPORATION IN-VIVO Plasmids |
| Zdroj: | Scopus-Elsevier |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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