title: Clinical testing of a dendritic cell targeted therapeutic vaccine in patients with chronic hepatitis C virus infection.
abstract: The lack of antiviral cellular immune responses in patients with chronic hepatitis C virus (HCV) infection suggests that T-cell vaccines may provide therapeutic benefit. Due to the central role that dendritic cells (DC) play in the activation of T-cell responses, our aim was to carry out a therapeutic vaccination clinical trial in HCV patients using DC. Five patients with chronic HCV infection were vaccinated with three doses of 5 × 10(6) or 10(7) autologous DC transduced with a recombinant adenovirus encoding NS3 using the adapter protein CFh40L, which facilitates DC transduction and maturation. No significant adverse effects were recorded after vaccination. Treatment caused no changes in serum liver enzymes nor in viral load. Vaccination induced weak but consistent expansion of T-cell responses against NS3 and adenoviral antigens. Patients' DC, as opposed to murine DC or DC from healthy subjects, secreted high IL-10 levels after transduction, inducing the activation of IL-10-producing T cells. IL-10 blockade during vaccine preparation restored its ability to stimulate anti-NS3 Th1 responses. Thus, vaccination with adenovirus-transduced DC is safe and induces weak antiviral immune responses. IL-10 associated with vaccine preparation may be partly responsible for these effects, suggesting that future vaccines should consider concomitant inhibition of this cytokine.
authors.affiliation: Division of Hepatology and Gene Therapy, Center for Applied Medical Research (CIMA), University of Navarra , Pamplona, Spain ; Instituto de Investigación Sanitaria de Navarra (IDISNA) , Pamplona, Spain.
authors.forename: Aintzane
authors.initials: A
authors.lastname: Zabaleta
authors.affiliation: Instituto de Investigación Sanitaria de Navarra (IDISNA) , Pamplona, Spain ; Liver Unit, Clínica Universidad de Navarra , Pamplona, Spain ; Centro de Investigación Biomédica en Red en el Área temática de Enfermedades Hepáticas y Digestivas (Ciberehd), Clínica Universidad de Navarra , Pamplona, Spain.
authors.forename: Delia
authors.initials: D
authors.lastname: D'Avola
authors.affiliation: Division of Hepatology and Gene Therapy, Center for Applied Medical Research (CIMA), University of Navarra , Pamplona, Spain ; Instituto de Investigación Sanitaria de Navarra (IDISNA) , Pamplona, Spain.
authors.forename: Itziar
authors.initials: I
authors.lastname: Echeverria
authors.affiliation: Division of Hepatology and Gene Therapy, Center for Applied Medical Research (CIMA), University of Navarra , Pamplona, Spain ; Instituto de Investigación Sanitaria de Navarra (IDISNA) , Pamplona, Spain.
authors.forename: Diana
authors.initials: D
authors.lastname: Llopiz
authors.affiliation: Division of Hepatology and Gene Therapy, Center for Applied Medical Research (CIMA), University of Navarra , Pamplona, Spain ; Instituto de Investigación Sanitaria de Navarra (IDISNA) , Pamplona, Spain.
authors.forename: Leyre
authors.initials: L
authors.lastname: Silva
authors.affiliation: Division of Hepatology and Gene Therapy, Center for Applied Medical Research (CIMA), University of Navarra , Pamplona, Spain ; Instituto de Investigación Sanitaria de Navarra (IDISNA) , Pamplona, Spain.
authors.forename: Lorea
authors.initials: L
authors.lastname: Villanueva
authors.affiliation: Division of Hepatology and Gene Therapy, Center for Applied Medical Research (CIMA), University of Navarra , Pamplona, Spain ; Instituto de Investigación Sanitaria de Navarra (IDISNA) , Pamplona, Spain.
authors.forename: José Ignacio
authors.initials: JI
authors.lastname: Riezu-Boj
authors.affiliation: Division of Hepatology and Gene Therapy, Center for Applied Medical Research (CIMA), University of Navarra , Pamplona, Spain ; Instituto de Investigación Sanitaria de Navarra (IDISNA) , Pamplona, Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: Larrea
authors.affiliation: Division of Hepatology and Gene Therapy, Center for Applied Medical Research (CIMA), University of Navarra , Pamplona, Spain ; Instituto de Investigación Sanitaria de Navarra (IDISNA) , Pamplona, Spain ; Division of Human Gene Therapy, Department of Medicine, University of Alabama at Birmingham , Birmingham, Alabama, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Pereboev
authors.affiliation: Division of Hepatology and Gene Therapy, Center for Applied Medical Research (CIMA), University of Navarra , Pamplona, Spain ; Instituto de Investigación Sanitaria de Navarra (IDISNA) , Pamplona, Spain.
authors.forename: Juan José
authors.initials: JJ
authors.lastname: Lasarte
authors.affiliation: Instituto de Investigación Sanitaria de Navarra (IDISNA) , Pamplona, Spain ; Liver Unit, Clínica Universidad de Navarra , Pamplona, Spain.
authors.forename: Iago
authors.initials: I
authors.lastname: Rodriguez-Lago
authors.affiliation: Instituto de Investigación Sanitaria de Navarra (IDISNA) , Pamplona, Spain ; Liver Unit, Clínica Universidad de Navarra , Pamplona, Spain ; Centro de Investigación Biomédica en Red en el Área temática de Enfermedades Hepáticas y Digestivas (Ciberehd), Clínica Universidad de Navarra , Pamplona, Spain.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Iñarrairaegui
authors.affiliation: Instituto de Investigación Sanitaria de Navarra (IDISNA) , Pamplona, Spain ; Liver Unit, Clínica Universidad de Navarra , Pamplona, Spain ; Centro de Investigación Biomédica en Red en el Área temática de Enfermedades Hepáticas y Digestivas (Ciberehd), Clínica Universidad de Navarra , Pamplona, Spain.
authors.forename: Bruno
authors.initials: B
authors.lastname: Sangro
authors.affiliation: Division of Hepatology and Gene Therapy, Center for Applied Medical Research (CIMA), University of Navarra , Pamplona, Spain ; Instituto de Investigación Sanitaria de Navarra (IDISNA) , Pamplona, Spain ; Liver Unit, Clínica Universidad de Navarra , Pamplona, Spain ; Centro de Investigación Biomédica en Red en el Área temática de Enfermedades Hepáticas y Digestivas (Ciberehd), Clínica Universidad de Navarra , Pamplona, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: Prieto
authors.affiliation: Division of Hepatology and Gene Therapy, Center for Applied Medical Research (CIMA), University of Navarra , Pamplona, Spain ; Instituto de Investigación Sanitaria de Navarra (IDISNA) , Pamplona, Spain.
authors.forename: Pablo
authors.initials: P
authors.lastname: Sarobe