Electroporation as a vaccine delivery system and a natural adjuvant to intradermal administration of plasmid DNA in macaques

Abstract

In vivo electroporation (EP) is used to enhance the uptake of nucleic acids and its association with DNA vaccination greatly stimulates immune responses to vaccine antigens delivered through the skin. However, the effect of EP on cutaneous cell behavior, the dynamics of immune cell recruitment and local inflammatory factors, have not been fully described. Here, we show that intradermal DNA vaccination combined with EP extends antigen expression to the epidermis and the subcutaneous skin muscle in non-human primates. In vivo fibered confocal microscopy and dynamic ex vivo imaging revealed that EP promotes the mobility of Langerhans cells (LC) and their interactions with transfected cells prior to their migration from the epidermis. At the peak of vaccine expression, we detected antigen in damaged keratinocyte areas in the epidermis and we characterized recruited immune cells in the skin, the hypodermis and the subcutaneous muscle. EP alone was sufficient to induce the production of pro-inflammatory cytokines in the skin and significantly increased local concentrations of Transforming Growth Factor (TGF)-alpha and IL-12. Our results show the kinetics of inflammatory processes in response to EP of the skin, and reveal its potential as a vaccine adjuvant.

DOI: 10.1038/s41598-017-04547-2

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Cite this paper

@inproceedings{Todorova2017ElectroporationAA, title={Electroporation as a vaccine delivery system and a natural adjuvant to intradermal administration of plasmid DNA in macaques}, author={Biliana Todorova and Lucille Adam and Slobodan Culina and Rapha{\"{e}l Boisgard and Fr{\'e}d{\'e}ric Martinon and Antonio Cosma and Mart Ustav and Thierry Kortulewski and Roger Le Grand and Catherine Chapon}, booktitle={Scientific reports}, year={2017} }