Innate Molecular and Cellular Signature in the Skin Preceding Long-Lasting T Cell Responses after Electroporated DNA Vaccination.

Autor:	Adam L; Immunology of Viral Infections and Autoimmune Diseases, Infectious Disease Models and Innovative Therapies Department, Commissariat à l'Energie Atomique et aux Energies Alternatives, Université Paris-Sud 11, INSERM U1184, 92265 Fontenay-aux-Roses, France., Tchitchek N; Immunology of Viral Infections and Autoimmune Diseases, Infectious Disease Models and Innovative Therapies Department, Commissariat à l'Energie Atomique et aux Energies Alternatives, Université Paris-Sud 11, INSERM U1184, 92265 Fontenay-aux-Roses, France., Todorova B; Immunology of Viral Infections and Autoimmune Diseases, Infectious Disease Models and Innovative Therapies Department, Commissariat à l'Energie Atomique et aux Energies Alternatives, Université Paris-Sud 11, INSERM U1184, 92265 Fontenay-aux-Roses, France., Rosenbaum P; Immunology of Viral Infections and Autoimmune Diseases, Infectious Disease Models and Innovative Therapies Department, Commissariat à l'Energie Atomique et aux Energies Alternatives, Université Paris-Sud 11, INSERM U1184, 92265 Fontenay-aux-Roses, France., Joly C; Immunology of Viral Infections and Autoimmune Diseases, Infectious Disease Models and Innovative Therapies Department, Commissariat à l'Energie Atomique et aux Energies Alternatives, Université Paris-Sud 11, INSERM U1184, 92265 Fontenay-aux-Roses, France., Poux C; Immunology of Viral Infections and Autoimmune Diseases, Infectious Disease Models and Innovative Therapies Department, Commissariat à l'Energie Atomique et aux Energies Alternatives, Université Paris-Sud 11, INSERM U1184, 92265 Fontenay-aux-Roses, France., Chapon C; Immunology of Viral Infections and Autoimmune Diseases, Infectious Disease Models and Innovative Therapies Department, Commissariat à l'Energie Atomique et aux Energies Alternatives, Université Paris-Sud 11, INSERM U1184, 92265 Fontenay-aux-Roses, France., Spetz AL; Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, SE-106 91 Stockholm, Sweden; and., Ustav M; Institute of Technology, University of Tartu, 50411 Tartu, Estonia., Le Grand R; Immunology of Viral Infections and Autoimmune Diseases, Infectious Disease Models and Innovative Therapies Department, Commissariat à l'Energie Atomique et aux Energies Alternatives, Université Paris-Sud 11, INSERM U1184, 92265 Fontenay-aux-Roses, France., Martinon F; Immunology of Viral Infections and Autoimmune Diseases, Infectious Disease Models and Innovative Therapies Department, Commissariat à l'Energie Atomique et aux Energies Alternatives, Université Paris-Sud 11, INSERM U1184, 92265 Fontenay-aux-Roses, France; frederic.martinon@cea.fr.
Jazyk:	angličtina
Zdroj:	Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2020 Jun 15; Vol. 204 (12), pp. 3375-3388. Date of Electronic Publication: 2020 May 08.
DOI:	10.4049/jimmunol.1900517
Abstrakt:	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 , or Mx1) , 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. (Copyright © 2020 by The American Association of Immunologists, Inc.)
Databáze:	MEDLINE
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