Scientific article
Open access

Lysosome-dependent activation of human dendritic cells by the vaccine adjuvant QS-21

Published inFrontiers in Immunology, vol. 7, 663
Publication date2017

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.

Affiliation Not a UNIGE publication
Citation (ISO format)
WELSBY, Iain et al. Lysosome-dependent activation of human dendritic cells by the vaccine adjuvant QS-21. In: Frontiers in Immunology, 2017, vol. 7, p. 663. doi: 10.3389/fimmu.2016.00663
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Article (Published version)
ISSN of the journal1664-3224

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