Comparison of DCs activation by virus-based vaccine delivery vectors emphasises the transcriptional downregulation of the oxidative phosphorylation pathway.

Antigen delivery platforms based on engineered viruses or virus like particles (VLPs) are currently developed as vaccines against infectious diseases. As the interaction of vaccines with dendritic cells (DCs) shapes the immunological response, we compared the interaction of a range of virus-based vectors and VLPs with DCs in a murine model of systemic administration and transcriptome analyses of splenic DC. The transcriptome profiles of DCs separated the vaccine vectors in two distinct groups characterised by high and low magnitude of differential gene expression, which strongly correlated with (i) the surface expression of co-stimulatory molecules CD40, CD83 and CD86 on DCs and (ii) antigen-specific T cell responses (Derian, N. et al 2016)1. Pathway analysis using PANOGA revealed that the JAK/STAT pathway was significantly activated by both groups of vaccines. In contrast, the oxidative phosphorylation pathway was significantly down regulated only by the high magnitude DC stimulating vectors. A gene signature including exclusively chemokine, cytokine and receptor related genes revealed a vector specific pattern. Overall this in vivo DC stimulation model demonstrated a strong relationship between the levels of induced DC maturation and the intensity of T-cell specific immune responses with distinct cytokine/chemokine profile, metabolic shifting and cell surface expression of maturation markers. It could represent an important tool for vaccine design.