Journal
FRONTIERS IN IMMUNOLOGY
Volume 7, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2016.00663
Keywords
vaccine; adjuvant; saponins; lysosome; cathepsins; dendritic cells; cytokine
Categories
Funding
- Walloon Region (DGO6)
- GlaxoSmithKline Biologicals SA
- Fonds National de la Recherche Scientifique (FRS-FNRS, Belgium)
- WELBIO
- Interuniversity Attraction Poles Programme of the Belgian Federal Science Policy
- FRS-FNRS (Belgium)
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The adjuvant properties of the saponin QS-21 have been known for decades. It is a component of the Adjuvant System AS01 that is used in several vaccine candidates. QS-21 strongly potentiates both cellular and humoral immune responses to purified antigens, yet how it activates immune cells is largely unknown. Here, we report that QS-21 directly activated human monocyte-derived dendritic cells (moDCs) and promoted a pro-inflammatory transcriptional program. Cholesterol-dependent QS-21 endocytosis followed by lysosomal destabilization and Syk kinase activation were prerequisites for this response. Cathepsin B, a lysosomal cysteine protease, was essential for moDC activation in vitro and contributed to the adjuvant effects of QS-21 in vivo. Collectively, these findings provide new insights into the pathways involved in the direct activation of antigen-presenting cells by a clinically relevant QS-21 formulation.
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