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Sci Rep. 2017 Jun 23;7(1):4122. doi: 10.1038/s41598-017-04547-2.

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

Author information

1
CEA - Université Paris Sud 11 - INSERM U1184, DRF/Jacob/Immunology of Viral infections and Autoimmune Diseases (IMVA), IDMIT infrastructure, 92265, Fontenay-aux-Roses, France.
2
Vaccine research institute (VRI), Créteil, France.
3
CEA, Institute of Biomedical Imaging (I2BM), DSV/SHFJ/INSERM U1023, CEA, Orsay, France.
4
Institute of Technology, University of Tartu, Tartu, Estonia.
5
CEA, Photonic Microscopy Platform, Institute of cellular and molecular radiation biology (IRCM), Fontenay-aux-Roses, France.
6
CEA - Université Paris Sud 11 - INSERM U1184, DRF/Jacob/Immunology of Viral infections and Autoimmune Diseases (IMVA), IDMIT infrastructure, 92265, Fontenay-aux-Roses, France. catherine.chapon@cea.fr.
7
Vaccine research institute (VRI), Créteil, France. catherine.chapon@cea.fr.

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.

PMID:
28646234
PMCID:
PMC5482824
DOI:
10.1038/s41598-017-04547-2
[Indexed for MEDLINE]
Free PMC Article

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