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Prototype development and preclinical immunogenicity analysis of a novel minimally invasive electroporation device

Gene Therapy volume 18, pages 258–265 (2011)Cite this article

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Abstract

The magnitude of the immune response to a DNA vaccine depends on three criteria—the optimized vector design, the use of a suitable adjuvant and the successful delivery and subsequent expression of the plasmid in the target tissue. In vivo electroporation (EP) has proved to be particularly effective in efficiently delivering DNA immunogens to the muscle and the skin, and indeed several devices have entered into human clinical trials. Here, we report on a novel concept of DNA delivery to the dermal tissue using a minimally invasive EP device, which is powered using low-voltage parameters. We show that this prototype device containing a novel 4 × 4-electrode array results in robust and reproducible transfection of dermal tissue and subsequent antigen expression at the injection site. Using DNA encoding for NP and M2e influenza antigens, we further show induction of potent cellular responses in a mouse model as measured by antigen-specific T-cell ELISpot assays. Importantly, 100% of the immunized animals were protected when challenged with VN/1203/04 (H5N1) strain of influenza. We have also extended our findings to a guinea-pig model and demonstrated induction of HI titers greater than 1:40 against a pandemic novel H1N1 virus showing proof of concept efficacy for DNA delivery with the prototype device in a broad spectrum of species and using multiple antigens. Finally, we were able to generate protective HI titers in macaques against the same novel H1N1 strain. Our results suggest that the minimally invasive dermal device may offer a safe, tolerable and efficient method to administer DNA vaccinations in a prophylactic setting, and thus potentially represents an important new option for improved DNA vaccine delivery in vivo.

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Acknowledgements

We thank Ben Guiterrez, Melissa Pope, Maria Yang and Janess Mendoza for technical help with plasmid preparation, assays and animal care and procedures. This work was supported, in part, by US Army grant number W23RYX-8141-N604: #08023003.

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Authors and Affiliations

  1. Inovio Pharmaceuticals, Research and Development, San Diego, CA, USA,

    K E Broderick, X Shen, J Soderholm, F Lin, J McCoy & S Kemmerrer

  2. Inovio Pharmaceuticals, Research and Development, Blue Bell, PA, USA

    A S Khan & N Y Sardesai

  3. Department of Pathology and Laboratory Medicine, University of Pennsylvania, Pennsylvania, PA, USA

    J Yan, M P Morrow & D B Weiner

  4. Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada,

    A Patel & G P Kobinger

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  1. K E Broderick
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  2. X Shen
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  4. F Lin
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  5. J McCoy
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  6. A S Khan
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  7. J Yan
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  10. G P Kobinger
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  12. D B Weiner
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  13. N Y Sardesai
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Correspondence to N Y Sardesai.

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Competing interests

The authors KEB, XS, FL, JM, AK, SK and NYS are employees of Inovio. DBW has possible commercial interest associated with this work, which may include Inovio, VGX, VGXi, Wyeth, BMS, Medarex, Virxsys, Ichor, Merck, Althea and Aldevron.

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Broderick, K., Shen, X., Soderholm, J. et al. Prototype development and preclinical immunogenicity analysis of a novel minimally invasive electroporation device. Gene Ther 18, 258–265 (2011). https://doi.org/10.1038/gt.2010.137

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  • DOI: https://doi.org/10.1038/gt.2010.137

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