Vaccination with helper-dependent adenovirus enhances the generation of transgene-specific ctl

Vaccination with helper-dependent adenovirus enhances the generation of transgene-specific ctl

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ABSTRACT Recombinant adenoviral vectors (AdV) have been used experimentally as vaccines to present antigenic transgenes _in vivo_. However, administration of first-generation vectors


(FG-AdV) is often limited by their induction of antiviral immunity. To address this limitation, helper-dependent vectors (HD-AdV) were developed that lack viral coding regions. While the


administration of HD-AdV results in long-term gene expression _in vivo_, their utility as immunogens has never been examined. Direct vaccination with 108 blue-forming units (BFU) of HD-AdV


injected into C57BL/6 mice lead to superior transgene-specific CTL and antibody responses when compared to the same amount of a FG-AdV. The antibody responses to viral antigens were high in


response to both the vectors. As a mechanism to reduce viral exposure, dendritic cells (DC) were transduced with HD-AdV _in vitro_ and then used as a cell-based vaccine. DC transduced with


HD-AdV expressed higher levels of transgene-specific mRNA and up to 1200-fold higher levels of transgene protein than did DC transduced with a FG-AdV. In addition, HD-AdV-transduced DC


stimulated superior transgene-specific CTL responses when administered _in vivo_, an effect that was further enhanced by maturing the DC with LPS prior to administration. In contrast to


direct immunization with HD-AdV, vaccination with HD-AdV-transduced DC was associated with limited antibody responses against the AdV. We conclude that HD-AdV stimulates superior


transgene-specific immune responses when compared to a FG-AdV, and that immunization with a DC-based vaccine maintains this efficacy while limiting antiviral reactivity. Access through your


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ACKNOWLEDGEMENTS Supported by grants from the Tobacco-Related Disease Research Program of California (SKB, 10KT-0086; MDR, #7RT-0040); the American Lung Association of California (SKB); the


UCLA Gene Therapy Program (SMK); and the UCLA Lung Cancer SPORE (NIH/NCI 1 P50 CA090388). AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Pulmonary & Critical Care Medicine, UCLA School of


Medicine, Los Angeles, CA, USA A Harui, M D Roth, S M Kiertscher & S K Basak * Microbiology, Immunology and Molecular Genetics, UCLA School of Medicine, Los Angeles, CA, USA K Mitani *


Jonsson Comprehensive Cancer Center, UCLA School of Medicine, Los Angeles, CA, USA M D Roth, S M Kiertscher & K Mitani Authors * A Harui View author publications You can also search for


this author inPubMed Google Scholar * M D Roth View author publications You can also search for this author inPubMed Google Scholar * S M Kiertscher View author publications You can also


search for this author inPubMed Google Scholar * K Mitani View author publications You can also search for this author inPubMed Google Scholar * S K Basak View author publications You can


also search for this author inPubMed Google Scholar RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Harui, A., Roth, M., Kiertscher, S. _et al._


Vaccination with helper-dependent adenovirus enhances the generation of transgene-specific CTL. _Gene Ther_ 11, 1617–1626 (2004). https://doi.org/10.1038/sj.gt.3302332 Download citation *


Received: 04 September 2003 * Accepted: 03 June 2004 * Published: 05 August 2004 * Issue Date: 01 November 2004 * DOI: https://doi.org/10.1038/sj.gt.3302332 SHARE THIS ARTICLE Anyone you


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Springer Nature SharedIt content-sharing initiative KEYWORDS * dendritic cells * vaccination * rodent * CTL