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Vaccines 2014, 2(2), 196-215; doi:10.3390/vaccines2020196
Article

Co-Administration of Molecular Adjuvants Expressing NF-Kappa B Subunit p65/RelA or Type-1 Transactivator T-bet Enhance Antigen Specific DNA Vaccine-Induced Immunity

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1 Department of Pathology & Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA 2 Inovio Pharmaceuticals Inc., 1787 Sentry Parkway West, Building 18, Suite 400, Blue Bell, PA 191422, USA 3 Department of Molecular Medicine, University of South Florida Morsani College of Medicine, Tampa, FL 33612, USA These authors contributed equally to this work.
* Author to whom correspondence should be addressed.
Received: 27 November 2013 / Revised: 31 January 2014 / Accepted: 28 February 2014 / Published: 25 March 2014
(This article belongs to the Special Issue DNA Vaccines)
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Abstract

DNA vaccine-induced immunity can be enhanced by the co-delivery of synthetic gene-encoding molecular adjuvants. Many of these adjuvants have included cytokines, chemokines or co-stimulatory molecules that have been demonstrated to enhance vaccine-induced immunity by increasing the magnitude or type of immune responses and/or protective efficacy. In this way, through the use of adjuvants, immune responses can be highly customizable and functionally tailored for optimal efficacy against pathogen specific (i.e., infectious agent) or non-pathogen (i.e., cancer) antigens. In the novel study presented here, we examined the use of cellular transcription factors as molecular adjuvants. Specifically the co-delivery of (a) RelA, a subunit of the NF-κB transcription complex or (b) T-bet, a Th1-specific T box transcription factor, along with a prototypical DNA vaccine expressing HIV-1 proteins was evaluated. As well, all of the vaccines and adjuvants were administered to mice using in vivo electroporation (EP), a technology demonstrated to dramatically increase plasmid DNA transfection and subsequent transgene expression with concomitant enhancement of vaccine induced immune responses. As such, this study demonstrated that co-delivery of either adjuvant resulted in enhanced T and B cell responses, specifically characterized by increased T cell numbers, IFN-γ production, as well as enhanced antibody responses. This study demonstrates the use of cellular transcription factors as adjuvants for enhancing DNA vaccine-induced immunity.
Keywords: DNA vaccine; transcription factors; adjuvant-enhanced immunity; T cell immunity; antibody responses DNA vaccine; transcription factors; adjuvant-enhanced immunity; T cell immunity; antibody responses
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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Shedlock, D.J.; Tingey, C.; Mahadevan, L.; Hutnick, N.; Reuschel, E.L.; Kudchodkar, S.; Flingai, S.; Yan, J.; Kim, J.J.; Ugen, K.E.; Weiner, D.B.; Muthumani, K. Co-Administration of Molecular Adjuvants Expressing NF-Kappa B Subunit p65/RelA or Type-1 Transactivator T-bet Enhance Antigen Specific DNA Vaccine-Induced Immunity. Vaccines 2014, 2, 196-215.

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