ABSTRACT: DNA vaccines delivered with electroporation have shown promising results in pre-clinical models and are evaluated in clinical trials. Here, we aim to characterize early mechanisms occuring in the skin after intradermal injection and electroporation of the auxoGTUmultiSIV DNA vaccine in non-human primates. Firstly, we show that electroporation acts as an adjuvant by enhancing local inflammation, notably via granulocytes, monocytes/macrophages and a CD1aint -expressing cell recruitment. Electroporation also induced Langerhans cell maturation, illustrated by CD86, CD83, and HLA-DR up-regulation, and their migration out of the epidermis. Secondly, we demonstrate the crucial role of the DNA vaccine in the soluble factors release, such as MCP-1 or IL-15. Transcriptomic analysis showed that electroporation played a major role in gene expression changes post-vaccination. However, the DNA vaccine is required to strongly up-regulate several genes involved in inflammatory responses (e.g Saa4), cell migration (e.g Ccl3, Ccl5 or Cxcl10), APC activation (e.g Cd86) and interferon-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 up-regulated, only in the presence of the DNA vaccine and trends to positively correlate with several interferon inducible genes, suggesting the potential role of AIM-2 in the 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 electroporation and the auxoGTUmultiSIV vaccine triggered different components of the innate immunity, led to strong and persistent cellular recall responses.
