Lysosome-Dependent Activation of Human Dendritic Cells by the Vaccine Adjuvant QS-21

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...

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Bibliographic Details
Published in:Frontiers in immunology 2017-01, Vol.7, p.663-663
Main Authors: 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
Format: Article
Language:English
Subjects:
Immunology
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Summary: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 and contributed to the adjuvant effects of QS-21 . 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.
ISSN:1664-3224
1664-3224
DOI:10.3389/fimmu.2016.00663