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 recruitm...

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Autores principales:	Biliana Todorova, Lucille Adam, Slobodan Culina, Raphaël Boisgard, Frédéric Martinon, Antonio Cosma, Mart Ustav, Thierry Kortulewski, Roger Le Grand, Catherine Chapon
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d6ef145983f04a4f905a9c10ea861c5e
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spelling	oai:doaj.org-article:d6ef145983f04a4f905a9c10ea861c5e2021-12-02T12:32:41ZElectroporation as a vaccine delivery system and a natural adjuvant to intradermal administration of plasmid DNA in macaques10.1038/s41598-017-04547-22045-2322https://doaj.org/article/d6ef145983f04a4f905a9c10ea861c5e2017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-04547-2https://doaj.org/toc/2045-2322Abstract 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.Biliana TodorovaLucille AdamSlobodan CulinaRaphaël BoisgardFrédéric MartinonAntonio CosmaMart UstavThierry KortulewskiRoger Le GrandCatherine ChaponNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Biliana Todorova Lucille Adam Slobodan Culina Raphaël Boisgard Frédéric Martinon Antonio Cosma Mart Ustav Thierry Kortulewski Roger Le Grand Catherine Chapon Electroporation as a vaccine delivery system and a natural adjuvant to intradermal administration of plasmid DNA in macaques
description	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.
format	article
author	Biliana Todorova Lucille Adam Slobodan Culina Raphaël Boisgard Frédéric Martinon Antonio Cosma Mart Ustav Thierry Kortulewski Roger Le Grand Catherine Chapon
author_facet	Biliana Todorova Lucille Adam Slobodan Culina Raphaël Boisgard Frédéric Martinon Antonio Cosma Mart Ustav Thierry Kortulewski Roger Le Grand Catherine Chapon
author_sort	Biliana Todorova
title	Electroporation as a vaccine delivery system and a natural adjuvant to intradermal administration of plasmid DNA in macaques
title_short	Electroporation as a vaccine delivery system and a natural adjuvant to intradermal administration of plasmid DNA in macaques
title_full	Electroporation as a vaccine delivery system and a natural adjuvant to intradermal administration of plasmid DNA in macaques
title_fullStr	Electroporation as a vaccine delivery system and a natural adjuvant to intradermal administration of plasmid DNA in macaques
title_full_unstemmed	Electroporation as a vaccine delivery system and a natural adjuvant to intradermal administration of plasmid DNA in macaques
title_sort	electroporation as a vaccine delivery system and a natural adjuvant to intradermal administration of plasmid dna in macaques
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/d6ef145983f04a4f905a9c10ea861c5e
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Electroporation as a vaccine delivery system and a natural adjuvant to intradermal administration of plasmid DNA in macaques

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