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Innate Molecular and Cellular Signature in the Skin Preceding Long-Lasting T Cell Responses after Electroporated DNA Vaccination
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Number of Authors: 112020 (English)In: Journal of Immunology, ISSN 0022-1767, E-ISSN 1550-6606, Vol. 204, no 12, p. 3375-3388Article in journal (Refereed) Published
Abstract [en]

DNA vaccines delivered with electroporation (EP) have shown promising results in preclinical models and are evaluated in clinical trials. In this study, we aim to characterize early mechanisms occurring in the skin after intradermal injection and EP of the auxoGTUmultiSIV DNA vaccine in nonhuman primates. First, we show that EP acts as an adjuvant by enhancing local inflammation, notably via granulocytes, monocytes/macrophages, and CD1a(int)-expressing cell recruitment. EP also induced Langerhans cell maturation, illustrated by CD86, CD83, and HLA-DR upregulation and their migration out of the epidermis. Second, we demonstrate the crucial role of the DNA vaccine in soluble factors release, such as MCP-1 or IL-15. Transcriptomic analysis showed that EP played a major role in gene expression changes postvaccination. However, the DNA vaccine is required to strongly upregulate several genes involved in inflammatory responses (e.g., Saa4), cell migration (e.g., Ccl3, Ccl5, or Cxcl10), APC activation (e.g., Cd86), and IFN-inducible genes (e.g., Ifit3, Ifit5, Irf7, Isg15, orMx1), illustrating an antiviral response signature. Also, AIM-2, a cytosolic DNA sensor, appeared to be strongly upregulated only in the presence of the DNA vaccine and trends to positively correlate with several IFN-inducible genes, suggesting the potential role of AIM-2 in vaccine sensing and the subsequent innate response activation leading to strong adaptive T cell responses. Overall, these results demonstrate that a combined stimulation of the immune response, in which EP and the auxoGTUmultiSIV vaccine triggered different components of the innate immunity, led to strong and persistent cellular recall responses.

Place, publisher, year, edition, pages
2020. Vol. 204, no 12, p. 3375-3388
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Biological Sciences Immunology in the medical area
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URN: urn:nbn:se:su:diva-183629DOI: 10.4049/jimmunol.1900517ISI: 000540261500030PubMedID: 32385135OAI: oai:DiVA.org:su-183629DiVA, id: diva2:1456070
Available from: 2020-07-31 Created: 2020-07-31 Last updated: 2022-03-02Bibliographically approved

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Rosenbaum, PierreSpetz, Anna-Lena

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Department of Molecular Biosciences, The Wenner-Gren Institute
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