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Shedlock DJ, Tingey C, Mahadevan L, et al. 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 (Basel). 2014;2(2):196-215doi: 10.3390/vaccines2020196.
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. (2014). 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, 2(2), 196-215. https://doi.org/10.3390/vaccines2020196
Shedlock, Devon J, et al. "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 vol. 2,2 (2014): 196-215. doi: https://doi.org/10.3390/vaccines2020196
Shedlock DJ, Tingey C, Mahadevan L, Hutnick N, Reuschel EL, Kudchodkar S, Flingai S, Yan J, Kim JJ, Ugen KE, Weiner DB, 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 (Basel). 2014 Mar 25;2(2):196-215. doi: 10.3390/vaccines2020196. PMID: 26344618; PMCID: PMC4494262.
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Vaccines (Basel). 2014 Mar 25;2(2):196-215. doi: 10.3390/vaccines2020196.

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

Devon J Shedlock, Colleen Tingey, Lavanya Mahadevan, Natalie Hutnick, Emma L Reuschel, Sagar Kudchodkar, Seleeke Flingai, Jenny Yan, Joseph J Kim, Kenneth E Ugen, David B Weiner, Kar Muthumani

Affiliations

  1. Department of Pathology & Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. [email protected].
  2. Department of Pathology & Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. [email protected].
  3. Department of Pathology & Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. [email protected].
  4. Department of Pathology & Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. [email protected].
  5. Department of Pathology & Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. [email protected].
  6. Department of Pathology & Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. [email protected].
  7. Department of Pathology & Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. [email protected].
  8. Department of Pathology & Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. [email protected].
  9. Inovio Pharmaceuticals Inc., 1787 Sentry Parkway West, Building 18, Suite 400, Blue Bell, PA 191422, USA. [email protected].
  10. Department of Molecular Medicine, University of South Florida Morsani College of Medicine, Tampa, FL 33612, USA. [email protected].
  11. Department of Pathology & Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. [email protected].
  12. Department of Pathology & Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. [email protected].

PMID: 26344618 PMCID: PMC4494262 DOI: 10.3390/vaccines2020196

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; T cell immunity; adjuvant-enhanced immunity; antibody responses; transcription factors

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