title: Vaccine adjuvant MF59 promotes retention of unprocessed antigen in lymph node macrophage compartments and follicular dendritic cells.
abstract: Ag retention within lymph nodes (LNs) upon vaccination is critical for the development of adaptive immune responses, because it facilitates the encounter of the Ag with cognate lymphocytes. During a secondary exposure of the immune system to an Ag, immune complexes (ICs) that contain the unprocessed Ag are captured by subcapsular sinus macrophages and are transferred onto follicular dendritic cells, where they persist for weeks, facilitating Ag presentation to cognate memory B cells. The impact of adjuvants on Ag retention within the draining LNs is unknown. In this article, we provide the first evidence, to our knowledge, that the oil-in-water emulsion adjuvant MF59 localizes in subcapsular sinus and medullary macrophage compartments of mouse draining LNs, where it persists for at least 2 wk. In addition, we demonstrate that MF59 promotes accumulation of the unprocessed Ag within these LN compartments and facilitates the consequent deposition of the IC-trapped Ag onto activated follicular dendritic cells. These findings correlate with the ability of MF59 to boost germinal center generation and Ag-specific Ab titers. Our data suggest that the adjuvant effect of MF59 is, at least in part, due to an enhancement of IC-bound Ag retention within the LN and offer insights to improve the efficacy of new vaccine adjuvants.
authors.affiliation: Novartis Vaccines and Diagnostics, 53100, Siena, Italy.
authors.forename: Rocco
authors.initials: R
authors.lastname: Cantisani
authors.affiliation: Novartis Vaccines and Diagnostics, 53100, Siena, Italy.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Pezzicoli
authors.affiliation: Novartis Vaccines and Diagnostics, 53100, Siena, Italy.
authors.forename: Rossella
authors.initials: R
authors.lastname: Cioncada
authors.affiliation: Novartis Vaccines and Diagnostics, 53100, Siena, Italy.
authors.forename: Carmine
authors.initials: C
authors.lastname: Malzone
authors.affiliation: Novartis Vaccines and Diagnostics, 53100, Siena, Italy.
authors.forename: Ennio
authors.initials: E
authors.lastname: De Gregorio
authors.affiliation: Novartis Vaccines and Diagnostics, 53100, Siena, Italy.
authors.forename: Ugo
authors.initials: U
authors.lastname: D'Oro
authors.affiliation: Novartis Vaccines and Diagnostics, 53100, Siena, Italy diego.piccioli@novartis.com.
authors.forename: Diego
authors.initials: D
authors.lastname: Piccioli
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D000941:Antigens / Q000276:immunology; D020566:Dendritic Cells, Follicular / Q000276:immunology*; D005434:Flow Cytometry; D008198:Lymph Nodes / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D011136:Polysorbates / Q000494:pharmacology; D013185:Squalene / Q000276:immunology* / Q000494:pharmacology
chemical_list: D000276:Adjuvants, Immunologic; D000941:Antigens; C089950:MF59 oil emulsion; D011136:Polysorbates; D013185:Squalene