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

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2017 Jan 21

PMID 28105029

Citations 52

Authors

Iain Welsby

Sophie Detienne

Francisca NKuli

Severine Thomas

Sandrine Wouters

Viviane Bechtold

Dominique De Wit

Romain Gineste

Thomas Reinheckel

Abdelatif Elouahabi

Pierre J Courtoy

Arnaud M Didierlaurent

Stanislas Goriely

Affiliations

Soon will be listed here.

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 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.

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