AUTHOR=Welsby Iain , Detienne Sophie , N’Kuli Francisca , Thomas Séverine , Wouters Sandrine , Bechtold Viviane , De Wit Dominique , Gineste Romain , Reinheckel Thomas , Elouahabi Abdelatif , Courtoy Pierre J. , Didierlaurent Arnaud M. , Goriely Stanislas TITLE=Lysosome-Dependent Activation of Human Dendritic Cells by the Vaccine Adjuvant QS-21 JOURNAL=Frontiers in Immunology VOLUME=7 YEAR=2017 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2016.00663 DOI=10.3389/fimmu.2016.00663 ISSN=1664-3224 ABSTRACT=

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.