title: Vaccine adjuvants alum and MF59 induce rapid recruitment of neutrophils and monocytes that participate in antigen transport to draining lymph nodes.
abstract: Vaccine adjuvants such as alum and the oil-in-water emulsion MF59 are used to enhance immune responses towards pure soluble antigens, but their mechanism of action is still largely unclear. Since most adjuvanted vaccines are administered intramuscularly, we studied immune responses in the mouse muscle and found that both adjuvants were potent inducers of chemokine production and promoted rapid recruitment of CD11b(+) cells. The earliest and most abundantly recruited cell type are neutrophils, followed by monocytes, eosinophils and later dendritic cells (DCs) and macrophages. Using fluorescent forms of MF59 and ovalbumin (OVA) antigen, we show that all recruited cell types take up both adjuvant and antigen to transport them to the draining lymph nodes (LNs). There, we found antigen-positive neutrophils and monocytes within hours of injection, later followed by B cells and DCs. Compared to alum, MF59-injection lead to a more prominent neutrophil recruitment and a more efficient antigen re-localization from the injection site to the LN. As antigen-transporting neutrophils were observed in draining LNs, we asked whether these cells play an essential role in MF59-mediated adjuvanticity. However, antibody-mediated neutrophil ablation left MF59-adjuvanticity unaltered. Further studies will reveal whether other single cell types are crucial or whether the different recruited cell populations are redundant with overlapping functions.
authors.affiliation: Novartis Vaccines and Diagnostics, Siena, Italy.
authors.forename: Samuele
authors.initials: S
authors.lastname: Calabro
authors.forename: Marco
authors.initials: M
authors.lastname: Tortoli
authors.forename: Barbara C
authors.initials: BC
authors.lastname: Baudner
authors.forename: Alessandra
authors.initials: A
authors.lastname: Pacitto
authors.forename: Mario
authors.initials: M
authors.lastname: Cortese
authors.forename: Derek T
authors.initials: DT
authors.lastname: O'Hagan
authors.forename: Ennio
authors.initials: E
authors.lastname: De Gregorio
authors.forename: Anja
authors.initials: A
authors.lastname: Seubert
authors.forename: Andreas
authors.initials: A
authors.lastname: Wack
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000536:Aluminum Hydroxide / Q000008:administration & dosage / Q000276:immunology*; D000818:Animals; D001693:Biological Transport, Active / Q000276:immunology; D002465:Cell Movement / Q000276:immunology*; D005260:Female; D007273:Injections, Intramuscular; D008198:Lymph Nodes / Q000276:immunology* / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009000:Monocytes / Q000276:immunology* / Q000473:pathology; D020556:Neutrophil Infiltration / Q000276:immunology*; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D011136:Polysorbates / Q000008:administration & dosage; D013185:Squalene / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; C089950:MF59 oil emulsion; D011136:Polysorbates; D000536:Aluminum Hydroxide; D013185:Squalene; D010047:Ovalbumin