Search: onr:"swepub:oai:DiVA.org:su-183629" >
Innate Molecular an...
Innate Molecular and Cellular Signature in the Skin Preceding Long-Lasting T Cell Responses after Electroporated DNA Vaccination
-
Adam, Lucille (author)
-
Tchitchek, Nicolas (author)
-
Todorova, Biliana (author)
-
show more...
-
Rosenbaum, Pierre (author)
-
Joly, Candie (author)
-
Poux, Candice (author)
-
Chapon, Catherine (author)
-
- Spetz, Anna-Lena (author)
- Stockholms universitet,Institutionen för molekylär biovetenskap, Wenner-Grens institut
-
Ustav, Mart (author)
-
Le Grand, Roger (author)
-
Martinon, Frédéric (author)
-
show less...
-
(creator_code:org_t)
- 2020-06-15
- 2020
- English.
-
In: Journal of Immunology. - : The American Association of Immunologists. - 0022-1767 .- 1550-6606. ; 204:12, s. 3375-3388
- Related links:
-
https://www.jimmunol...
-
show more...
-
https://urn.kb.se/re...
-
https://doi.org/10.4...
-
show less...
Abstract
Subject headings
Close
- 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.
Subject headings
- NATURVETENSKAP -- Biologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
Find in a library
To the university's database
- By the author/editor
-
Adam, Lucille
-
Tchitchek, Nicol ...
-
Todorova, Bilian ...
-
Rosenbaum, Pierr ...
-
Joly, Candie
-
Poux, Candice
-
show more...
-
Chapon, Catherin ...
-
Spetz, Anna-Lena
-
Ustav, Mart
-
Le Grand, Roger
-
Martinon, Frédér ...
-
show less...
- About the subject
-
- NATURAL SCIENCES
-
NATURAL SCIENCES
-
and Biological Scien ...
-
- MEDICAL AND HEALTH SCIENCES
-
MEDICAL AND HEAL ...
-
and Basic Medicine
-
and Immunology in th ...
- Articles in the publication
-
Journal of Immun ...
- By the university
-
Stockholm University