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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...

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Autores principales: Zabaleta, Aintzane, D’Avola, Delia, Echeverria, Itziar, Llopiz, Diana, Silva, Leyre, Villanueva, Lorea, Riezu-Boj, José Ignacio, Larrea, Esther, Pereboev, Alexander, Lasarte, Juan José, Rodriguez-Lago, Iago, Iñarrairaegui, Mercedes, Sangro, Bruno, Prieto, Jesús, Sarobe, Pablo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4444996/
https://www.ncbi.nlm.nih.gov/pubmed/26029717
http://dx.doi.org/10.1038/mtm.2015.6
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author Zabaleta, Aintzane
D’Avola, Delia
Echeverria, Itziar
Llopiz, Diana
Silva, Leyre
Villanueva, Lorea
Riezu-Boj, José Ignacio
Larrea, Esther
Pereboev, Alexander
Lasarte, Juan José
Rodriguez-Lago, Iago
Iñarrairaegui, Mercedes
Sangro, Bruno
Prieto, Jesús
Sarobe, Pablo
author_facet Zabaleta, Aintzane
D’Avola, Delia
Echeverria, Itziar
Llopiz, Diana
Silva, Leyre
Villanueva, Lorea
Riezu-Boj, José Ignacio
Larrea, Esther
Pereboev, Alexander
Lasarte, Juan José
Rodriguez-Lago, Iago
Iñarrairaegui, Mercedes
Sangro, Bruno
Prieto, Jesús
Sarobe, Pablo
author_sort Zabaleta, Aintzane
collection PubMed
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 × 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.
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spelling pubmed-44449962015-05-29 Clinical testing of a dendritic cell targeted therapeutic vaccine in patients with chronic hepatitis C virus infection Zabaleta, Aintzane D’Avola, Delia Echeverria, Itziar Llopiz, Diana Silva, Leyre Villanueva, Lorea Riezu-Boj, José Ignacio Larrea, Esther Pereboev, Alexander Lasarte, Juan José Rodriguez-Lago, Iago Iñarrairaegui, Mercedes Sangro, Bruno Prieto, Jesús Sarobe, Pablo Mol Ther Methods Clin Dev Article 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. Nature Publishing Group 2015-03-11 /pmc/articles/PMC4444996/ /pubmed/26029717 http://dx.doi.org/10.1038/mtm.2015.6 Text en Copyright © 2015 American Society of Gene & Cell Therapy http://creativecommons.org/licenses/by-nc-sa/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/4.0/
spellingShingle Article
Zabaleta, Aintzane
D’Avola, Delia
Echeverria, Itziar
Llopiz, Diana
Silva, Leyre
Villanueva, Lorea
Riezu-Boj, José Ignacio
Larrea, Esther
Pereboev, Alexander
Lasarte, Juan José
Rodriguez-Lago, Iago
Iñarrairaegui, Mercedes
Sangro, Bruno
Prieto, Jesús
Sarobe, Pablo
Clinical testing of a dendritic cell targeted therapeutic vaccine in patients with chronic hepatitis C virus infection
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
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4444996/
https://www.ncbi.nlm.nih.gov/pubmed/26029717
http://dx.doi.org/10.1038/mtm.2015.6
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