Open AccessCentral Role of CD169+ Lymph Node Resident Macrophages in the Adjuvanticity of the QS-21 Component of AS01
Author(s) -
Sophie Detienne,
Iain Welsby,
Catherine Collig,
Sandrine Wouters,
Margherita Coccia,
Sophie Delhaye,
Laurye Van Maele,
Séverine Thomas,
Maëlle Swertvaegher,
Aurélie Detavernier,
Abdelatif Elouahabi,
Stanislas Goriely,
Arnaud M. Didierlaurent
Publication year - 2016
Publication title -
scientific reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.24
H-Index - 213
ISSN - 2045-2322
DOI - 10.1038/srep39475
Subject(s) - adjuvant , lymph node , innate immune system , hmgb1 , immunology , immune system , medicine , priming (agriculture) , antigen , lymph , macrophage , biology , pathology , inflammation , in vitro , botany , germination , biochemistry
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.