title: Lysosome-Dependent Activation of Human Dendritic Cells by the Vaccine Adjuvant QS-21.
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 activationin vitroand contributed to the adjuvant effects of QS-21in 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.
authors.affiliation: Institute for Medical Immunology, Université Libre de Bruxelles (ULB) , Gosselies , Belgium.
authors.forename: Iain
authors.initials: I
authors.lastname: Welsby
authors.affiliation: Institute for Medical Immunology, Université Libre de Bruxelles (ULB) , Gosselies , Belgium.
authors.forename: Sophie
authors.initials: S
authors.lastname: Detienne
authors.affiliation: Cell Biology Unit, de Duve Institute, Université Catholique de Louvain , Brussels , Belgium.
authors.forename: Francisca
authors.initials: F
authors.lastname: N'Kuli
authors.affiliation: Institute for Medical Immunology, Université Libre de Bruxelles (ULB) , Gosselies , Belgium.
authors.forename: Séverine
authors.initials: S
authors.lastname: Thomas
authors.affiliation: GSK Vaccines , Rixensart , Belgium.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Wouters
authors.affiliation: GSK Vaccines , Rixensart , Belgium.
authors.forename: Viviane
authors.initials: V
authors.lastname: Bechtold
authors.affiliation: Institute for Medical Immunology, Université Libre de Bruxelles (ULB) , Gosselies , Belgium.
authors.forename: Dominique
authors.initials: D
authors.lastname: De Wit
authors.affiliation: GSK Vaccines , Rixensart , Belgium.
authors.forename: Romain
authors.initials: R
authors.lastname: Gineste
authors.affiliation: Medical Faculty, Institute for Molecular Medicine and Cell Research, Albert Ludwigs University , Freiburg , Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Reinheckel
authors.affiliation: GSK Vaccines , Rixensart , Belgium.
authors.forename: Abdelatif
authors.initials: A
authors.lastname: Elouahabi
authors.affiliation: Cell Biology Unit, de Duve Institute, Université Catholique de Louvain , Brussels , Belgium.
authors.forename: Pierre J
authors.initials: PJ
authors.lastname: Courtoy
authors.affiliation: GSK Vaccines , Rixensart , Belgium.
authors.forename: Arnaud M
authors.initials: AM
authors.lastname: Didierlaurent
authors.affiliation: Institute for Medical Immunology, Université Libre de Bruxelles (ULB) , Gosselies , Belgium.
authors.forename: Stanislas
authors.initials: S
authors.lastname: Goriely
keywords: adjuvant; cathepsins; cytokine; dendritic cells; lysosome; saponins; vaccine