title: Enhancement of adaptive immunity by the human vaccine adjuvant AS01 depends on activated dendritic cells.
abstract: Adjuvant System AS01 is a liposome-based vaccine adjuvant containing 3-O-desacyl-4'-monophosphoryl lipid A and the saponin QS-21. AS01 has been selected for the clinical development of several candidate vaccines including the RTS,S malaria vaccine and the subunit glycoprotein E varicella zoster vaccine (both currently in phase III). Given the known immunostimulatory properties of MPL and QS-21, the objective of this study was to describe the early immune response parameters after immunization with an AS01-adjuvanted vaccine and to identify relationships with the vaccine-specific adaptive immune response. Cytokine production and innate immune cell recruitment occurred rapidly and transiently at the muscle injection site and draining lymph node postinjection, consistent with the rapid drainage of the vaccine components to the draining lymph node. The induction of Ag-specific Ab and T cell responses was dependent on the Ag being injected at the same time or within 24 h after AS01, suggesting that the early events occurring postinjection were required for these elevated adaptive responses. In the draining lymph node, after 24 h, the numbers of activated and Ag-loaded monocytes and MHCII(high) dendritic cells were higher after the injection of the AS01-adjuvanted vaccine than after Ag alone. However, only MHCII(high) dendritic cells appeared efficient at and necessary for direct Ag presentation to T cells. These data suggest that the ability of AS01 to improve adaptive immune responses, as has been demonstrated in clinical trials, is linked to a transient stimulation of the innate immune system leading to the generation of high number of efficient Ag-presenting dendritic cells.
authors.affiliation: GlaxoSmithKline Vaccines, 1330 Rixensart, Belgium; arnaud.x.didierlaurent@gsk.com.
authors.forename: Arnaud M
authors.initials: AM
authors.lastname: Didierlaurent
authors.affiliation: GlaxoSmithKline Vaccines, 1330 Rixensart, Belgium;
authors.forename: Catherine
authors.initials: C
authors.lastname: Collignon
authors.affiliation: GlaxoSmithKline Vaccines, 1330 Rixensart, Belgium;
authors.forename: Patricia
authors.initials: P
authors.lastname: Bourguignon
authors.affiliation: GlaxoSmithKline Vaccines, 1330 Rixensart, Belgium;
authors.forename: Sandrine
authors.initials: S
authors.lastname: Wouters
authors.affiliation: Vlaams Instituut voor Biotechnologie Inflammation Research Center, Ghent University, 9052 Ghent, Belgium; and.
authors.forename: Kaat
authors.initials: K
authors.lastname: Fierens
authors.affiliation: GlaxoSmithKline Vaccines, 1330 Rixensart, Belgium;
authors.forename: Michel
authors.initials: M
authors.lastname: Fochesato
authors.affiliation: GlaxoSmithKline Vaccines, 1330 Rixensart, Belgium;
authors.forename: Najoua
authors.initials: N
authors.lastname: Dendouga
authors.affiliation: GlaxoSmithKline Vaccines, 1330 Rixensart, Belgium;
authors.forename: Christelle
authors.initials: C
authors.lastname: Langlet
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Aix-Marseille Université, INSERM U1104, Centre National de la Recherche Scientifique Unité Mixte de Recherche 7280, 13288 Marseille cedex 9, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Malissen
authors.affiliation: Vlaams Instituut voor Biotechnologie Inflammation Research Center, Ghent University, 9052 Ghent, Belgium; and.
authors.forename: Bart N
authors.initials: BN
authors.lastname: Lambrecht
authors.affiliation: GlaxoSmithKline Vaccines, 1330 Rixensart, Belgium;
authors.forename: Nathalie
authors.initials: N
authors.lastname: Garçon
authors.affiliation: GlaxoSmithKline Vaccines, 1330 Rixensart, Belgium;
authors.forename: Marcelle
authors.initials: M
authors.lastname: Van Mechelen
authors.affiliation: GlaxoSmithKline Vaccines, 1330 Rixensart, Belgium;
authors.forename: Sandra
authors.initials: S
authors.lastname: Morel
mesh_terms: D056704:Adaptive Immunity / Q000276:immunology*; D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D004338:Drug Combinations; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D008050:Lipid A / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000276:immunology; D012503:Saponins / Q000008:administration & dosage* / Q000276:immunology*; D014611:Vaccination; D014612:Vaccines / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D004338:Drug Combinations; D000949:Histocompatibility Antigens Class II; D008050:Lipid A; D012503:Saponins; D014612:Vaccines; C000592464:adjuvant system 01; C078785:saponin QA-21V1; C048436:monophosphoryl lipid A