title: Central Role of CD169+Lymph Node Resident Macrophages in the Adjuvanticity of the QS-21 Component of AS01.
abstract: Saponins represent a promising class of vaccine adjuvant. Together with the TLR4-ligand MPL, QS-21 is part of the Adjuvant System AS01, a key component of the malaria and zoster candidate vaccines that display demonstrated clinical efficacy. However, the mechanism of action of QS-21 in this liposomal formulation is poorly understood. Upon intra-muscular immunisation, we observed that QS-21 rapidly accumulated in CD169+resident macrophages of the draining lymph node where it elicited a local innate immune response. Depletion of these cells abrogated QS-21-mediated innate cell recruitment to the lymph node, dendritic cell (DC) phenotypic maturation as well as the adjuvant effect on T-cell and antibody responses to co-administered antigens. DCs rather than lymph node-resident macrophages were directly involved in T-cell priming by QS-21, as revealed by the decrease in antigen-specific T-cell response in Batf3-/-mice. Further analysis showed that the adjuvant effect of QS-21 depended on the integration of Caspase-1 and MyD88 pathways, at least in part through the local release of HMGB1. Taken together, this work unravels the key role of lymph node sentinel macrophage in controlling the adjuvant effect of a molecule proven to improve vaccine response in humans.
authors.affiliation: Institute for Medical Immunology (IMI), Université Libre de Bruxelles, Rue Adrienne Bolland 8, B-6041 Gosselies, Belgium.
authors.forename: Sophie
authors.initials: S
authors.lastname: Detienne
authors.affiliation: Institute for Medical Immunology (IMI), Université Libre de Bruxelles, Rue Adrienne Bolland 8, B-6041 Gosselies, Belgium.
authors.forename: Iain
authors.initials: I
authors.lastname: Welsby
authors.affiliation: GSK Vaccines, Rue de l'Institut 89, B-1330 Rixensart, Belgium.
authors.forename: Catherine
authors.initials: C
authors.lastname: Collignon
authors.affiliation: GSK Vaccines, Rue de l'Institut 89, B-1330 Rixensart, Belgium.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Wouters
authors.affiliation: GSK Vaccines, Rue de l'Institut 89, B-1330 Rixensart, Belgium.
authors.forename: Margherita
authors.initials: M
authors.lastname: Coccia
authors.affiliation: GSK Vaccines, Rue de l'Institut 89, B-1330 Rixensart, Belgium.
authors.forename: Sophie
authors.initials: S
authors.lastname: Delhaye
authors.affiliation: Institute for Medical Immunology (IMI), Université Libre de Bruxelles, Rue Adrienne Bolland 8, B-6041 Gosselies, Belgium.
authors.forename: Laurye
authors.initials: L
authors.lastname: Van Maele
authors.affiliation: Institute for Medical Immunology (IMI), Université Libre de Bruxelles, Rue Adrienne Bolland 8, B-6041 Gosselies, Belgium.
authors.forename: Séverine
authors.initials: S
authors.lastname: Thomas
authors.affiliation: Institute for Medical Immunology (IMI), Université Libre de Bruxelles, Rue Adrienne Bolland 8, B-6041 Gosselies, Belgium.
authors.forename: Maëlle
authors.initials: M
authors.lastname: Swertvaegher
authors.affiliation: Institute for Medical Immunology (IMI), Université Libre de Bruxelles, Rue Adrienne Bolland 8, B-6041 Gosselies, Belgium.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Detavernier
authors.affiliation: GSK Vaccines, Rue de l'Institut 89, B-1330 Rixensart, Belgium.
authors.forename: Abdelatif
authors.initials: A
authors.lastname: Elouahabi
authors.affiliation: Institute for Medical Immunology (IMI), Université Libre de Bruxelles, Rue Adrienne Bolland 8, B-6041 Gosselies, Belgium.
authors.forename: Stanislas
authors.initials: S
authors.lastname: Goriely
authors.affiliation: GSK Vaccines, Rue de l'Institut 89, B-1330 Rixensart, Belgium.
authors.forename: Arnaud M
authors.initials: AM
authors.lastname: Didierlaurent