Antigen Gene Transfer to Human Plasmacytoid Dendritic Cells Using Recombinant Adenovirus and Vaccinia Virus Vectors

Recombinant adenoviruses (RAd) and recombinant vaccinia viruses (RVV) expressing tumour-associated antigens (TAA) are used as anti-tumour vaccines. It is important that these vaccines deliver the TAA to dendritic cells (DC) for the induction of a strong immune response. Infection of myeloid DC (MDC)...

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Main Authors: Hetty J. Bontkes, Janneke J. Ruizendaal, Marco W. J. Schreurs, Duco Kramer, Chris J. L. M. Meijer, Erik Hooijberg
Format: Article
Language:English
Published: Wiley 2005-01-01
Series:Cellular Oncology
Online Access:http://dx.doi.org/10.1155/2005/753549
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author Hetty J. Bontkes
Janneke J. Ruizendaal
Marco W. J. Schreurs
Duco Kramer
Chris J. L. M. Meijer
Erik Hooijberg
author_facet Hetty J. Bontkes
Janneke J. Ruizendaal
Marco W. J. Schreurs
Duco Kramer
Chris J. L. M. Meijer
Erik Hooijberg
author_sort Hetty J. Bontkes
collection DOAJ
description Recombinant adenoviruses (RAd) and recombinant vaccinia viruses (RVV) expressing tumour-associated antigens (TAA) are used as anti-tumour vaccines. It is important that these vaccines deliver the TAA to dendritic cells (DC) for the induction of a strong immune response. Infection of myeloid DC (MDC) with RAd alone is relatively inefficient but CD40 retargeting significantly increases transduction efficiency and DC maturation. Infection with RVV is efficient without DC maturation. Plasmacytoid dendritic cells (PDC) play a role in the innate immune response to viral infections through the secretion of IFNα but may also play a role in specific T-cell induction. The aim of our study was to investigate whether PDC are better targets for RAd and RVV based vaccines. RAd alone hardly infected PDC (2%) while CD40 retargeting did not improve transduction efficiency, but it did increase PDC maturation (25% CD83 positive cells). Accordingly, specific CTL activation by RAd infected PDC was limited (the number of IFNγ producing CTL was reduced by 75% compared to stimulation with peptide loaded PDC). RVV infected PDC specifically stimulated CTL but PDC were not activated. These Results indicate that PDC are not ideal targets for RAd and RVV based vaccines. However, PDC induced specific CTL activation after pulsing with recombinant protein, indicating that PDC can also cross-present antigens released from surrounding infected cells.
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spelling doaj-art-24bbaeb7d7cf41edb9105be86f93715e2025-02-03T05:59:22ZengWileyCellular Oncology1570-58701875-86062005-01-0127317518210.1155/2005/753549Antigen Gene Transfer to Human Plasmacytoid Dendritic Cells Using Recombinant Adenovirus and Vaccinia Virus VectorsHetty J. Bontkes0Janneke J. Ruizendaal1Marco W. J. Schreurs2Duco Kramer3Chris J. L. M. Meijer4Erik Hooijberg5Department of Pathology, VU University Medical Center, 1081 HV Amsterdam, The NetherlandsDepartment of Pathology, VU University Medical Center, 1081 HV Amsterdam, The NetherlandsDepartment of Pathology, VU University Medical Center, 1081 HV Amsterdam, The NetherlandsDepartment of Pathology, VU University Medical Center, 1081 HV Amsterdam, The NetherlandsDepartment of Pathology, VU University Medical Center, 1081 HV Amsterdam, The NetherlandsDepartment of Pathology, VU University Medical Center, 1081 HV Amsterdam, The NetherlandsRecombinant adenoviruses (RAd) and recombinant vaccinia viruses (RVV) expressing tumour-associated antigens (TAA) are used as anti-tumour vaccines. It is important that these vaccines deliver the TAA to dendritic cells (DC) for the induction of a strong immune response. Infection of myeloid DC (MDC) with RAd alone is relatively inefficient but CD40 retargeting significantly increases transduction efficiency and DC maturation. Infection with RVV is efficient without DC maturation. Plasmacytoid dendritic cells (PDC) play a role in the innate immune response to viral infections through the secretion of IFNα but may also play a role in specific T-cell induction. The aim of our study was to investigate whether PDC are better targets for RAd and RVV based vaccines. RAd alone hardly infected PDC (2%) while CD40 retargeting did not improve transduction efficiency, but it did increase PDC maturation (25% CD83 positive cells). Accordingly, specific CTL activation by RAd infected PDC was limited (the number of IFNγ producing CTL was reduced by 75% compared to stimulation with peptide loaded PDC). RVV infected PDC specifically stimulated CTL but PDC were not activated. These Results indicate that PDC are not ideal targets for RAd and RVV based vaccines. However, PDC induced specific CTL activation after pulsing with recombinant protein, indicating that PDC can also cross-present antigens released from surrounding infected cells.http://dx.doi.org/10.1155/2005/753549
spellingShingle Hetty J. Bontkes
Janneke J. Ruizendaal
Marco W. J. Schreurs
Duco Kramer
Chris J. L. M. Meijer
Erik Hooijberg
Antigen Gene Transfer to Human Plasmacytoid Dendritic Cells Using Recombinant Adenovirus and Vaccinia Virus Vectors
Cellular Oncology
title Antigen Gene Transfer to Human Plasmacytoid Dendritic Cells Using Recombinant Adenovirus and Vaccinia Virus Vectors
title_full Antigen Gene Transfer to Human Plasmacytoid Dendritic Cells Using Recombinant Adenovirus and Vaccinia Virus Vectors
title_fullStr Antigen Gene Transfer to Human Plasmacytoid Dendritic Cells Using Recombinant Adenovirus and Vaccinia Virus Vectors
title_full_unstemmed Antigen Gene Transfer to Human Plasmacytoid Dendritic Cells Using Recombinant Adenovirus and Vaccinia Virus Vectors
title_short Antigen Gene Transfer to Human Plasmacytoid Dendritic Cells Using Recombinant Adenovirus and Vaccinia Virus Vectors
title_sort antigen gene transfer to human plasmacytoid dendritic cells using recombinant adenovirus and vaccinia virus vectors
url http://dx.doi.org/10.1155/2005/753549
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