Clinical testing of a dendritic cell targeted therapeutic vaccine in patients with chronic hepatitis C virus infection
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 therapeut...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2015-01-01
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| Series: | Molecular Therapy: Methods & Clinical Development |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2329050116300183 |
| _version_ | 1828385702651363328 |
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| author | Aintzane Zabaleta Delia D'Avola Itziar Echeverria Diana Llopiz Leyre Silva Lorea Villanueva José Ignacio Riezu-Boj Esther Larrea Alexander Pereboev Juan José Lasarte Iago Rodriguez-Lago Mercedes Iñarrairaegui Bruno Sangro Jesús Prieto Pablo Sarobe |
| author_facet | Aintzane Zabaleta Delia D'Avola Itziar Echeverria Diana Llopiz Leyre Silva Lorea Villanueva José Ignacio Riezu-Boj Esther Larrea Alexander Pereboev Juan José Lasarte Iago Rodriguez-Lago Mercedes Iñarrairaegui Bruno Sangro Jesús Prieto Pablo Sarobe |
| author_sort | Aintzane Zabaleta |
| collection | DOAJ |
| description | 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 Ã 106 or 107 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. Patientsâ DC, as opposed to murine DC or DC from healthy subjects, secreted high IL-10 levels after transduction, inducing the activation of IL-10âproducing 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. |
| first_indexed | 2024-12-10T05:24:30Z |
| format | Article |
| id | doaj.art-a824b1a51cd6450d8b80d26a263f2b52 |
| institution | Directory Open Access Journal |
| issn | 2329-0501 |
| language | English |
| last_indexed | 2024-12-10T05:24:30Z |
| publishDate | 2015-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Methods & Clinical Development |
| spelling | doaj.art-a824b1a51cd6450d8b80d26a263f2b522022-12-22T02:00:43ZengElsevierMolecular Therapy: Methods & Clinical Development2329-05012015-01-012Clinical testing of a dendritic cell targeted therapeutic vaccine in patients with chronic hepatitis C virus infectionAintzane Zabaleta0Delia D'Avola1Itziar Echeverria2Diana Llopiz3Leyre Silva4Lorea Villanueva5José Ignacio Riezu-Boj6Esther Larrea7Alexander Pereboev8Juan José Lasarte9Iago Rodriguez-Lago10Mercedes Iñarrairaegui11Bruno Sangro12Jesús Prieto13Pablo Sarobe14Division of Hepatology and Gene Therapy, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain; Instituto de Investigación Sanitaria de Navarra (IDISNA), Pamplona, SpainInstituto de Investigación Sanitaria de Navarra (IDISNA), Pamplona, Spain; Liver Unit, ClÃnica Universidad de Navarra, Pamplona, Spain; Centro de Investigación Biomédica en Red en el Ãrea temática de Enfermedades Hepáticas y Digestivas (Ciberehd), ClÃnica Universidad de Navarra, Pamplona, SpainDivision of Hepatology and Gene Therapy, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain; Instituto de Investigación Sanitaria de Navarra (IDISNA), Pamplona, SpainDivision of Hepatology and Gene Therapy, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain; Instituto de Investigación Sanitaria de Navarra (IDISNA), Pamplona, SpainDivision of Hepatology and Gene Therapy, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain; Instituto de Investigación Sanitaria de Navarra (IDISNA), Pamplona, SpainDivision of Hepatology and Gene Therapy, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain; Instituto de Investigación Sanitaria de Navarra (IDISNA), Pamplona, SpainDivision of Hepatology and Gene Therapy, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain; Instituto de Investigación Sanitaria de Navarra (IDISNA), Pamplona, SpainDivision of Hepatology and Gene Therapy, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain; Instituto de Investigación Sanitaria de Navarra (IDISNA), Pamplona, SpainDivision 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, USADivision of Hepatology and Gene Therapy, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain; Instituto de Investigación Sanitaria de Navarra (IDISNA), Pamplona, SpainInstituto de Investigación Sanitaria de Navarra (IDISNA), Pamplona, Spain; Liver Unit, ClÃnica Universidad de Navarra, Pamplona, SpainInstituto de Investigación Sanitaria de Navarra (IDISNA), Pamplona, Spain; Liver Unit, ClÃnica Universidad de Navarra, Pamplona, Spain; Centro de Investigación Biomédica en Red en el Ãrea temática de Enfermedades Hepáticas y Digestivas (Ciberehd), ClÃnica Universidad de Navarra, Pamplona, SpainInstituto de Investigación Sanitaria de Navarra (IDISNA), Pamplona, Spain; Liver Unit, ClÃnica Universidad de Navarra, Pamplona, Spain; Centro de Investigación Biomédica en Red en el Ãrea temática de Enfermedades Hepáticas y Digestivas (Ciberehd), ClÃnica Universidad de Navarra, Pamplona, SpainDivision 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, ClÃnica Universidad de Navarra, Pamplona, Spain; Centro de Investigación Biomédica en Red en el Ãrea temática de Enfermedades Hepáticas y Digestivas (Ciberehd), ClÃnica Universidad de Navarra, Pamplona, SpainDivision of Hepatology and Gene Therapy, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain; Instituto de Investigación Sanitaria de Navarra (IDISNA), Pamplona, SpainThe 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 à 106 or 107 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. Patientsâ DC, as opposed to murine DC or DC from healthy subjects, secreted high IL-10 levels after transduction, inducing the activation of IL-10âproducing 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.http://www.sciencedirect.com/science/article/pii/S2329050116300183 |
| spellingShingle | Aintzane Zabaleta Delia D'Avola Itziar Echeverria Diana Llopiz Leyre Silva Lorea Villanueva José Ignacio Riezu-Boj Esther Larrea Alexander Pereboev Juan José Lasarte Iago Rodriguez-Lago Mercedes Iñarrairaegui Bruno Sangro Jesús Prieto Pablo Sarobe Clinical testing of a dendritic cell targeted therapeutic vaccine in patients with chronic hepatitis C virus infection Molecular Therapy: Methods & Clinical Development |
| title | Clinical testing of a dendritic cell targeted therapeutic vaccine in patients with chronic hepatitis C virus infection |
| title_full | Clinical testing of a dendritic cell targeted therapeutic vaccine in patients with chronic hepatitis C virus infection |
| title_fullStr | Clinical testing of a dendritic cell targeted therapeutic vaccine in patients with chronic hepatitis C virus infection |
| title_full_unstemmed | Clinical testing of a dendritic cell targeted therapeutic vaccine in patients with chronic hepatitis C virus infection |
| title_short | Clinical testing of a dendritic cell targeted therapeutic vaccine in patients with chronic hepatitis C virus infection |
| title_sort | clinical testing of a dendritic cell targeted therapeutic vaccine in patients with chronic hepatitis c virus infection |
| url | http://www.sciencedirect.com/science/article/pii/S2329050116300183 |
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