title: Vaccination with liposomal poly(I:C) induces discordant maturation of migratory dendritic cell subsets and anti-viral gene signatures in afferent lymph cells.
abstract: Vaccine formulations administered in the periphery must activate naive immune cells within the lymph node. In this study, we have directly cannulated the ovine lymphatic vessels to investigate the cellular and molecular mechanisms that transfer information from the periphery into the local draining lymph node via the afferent lymph. Inclusion of poly(I:C) into a liposomal vaccine formulation enhances the neutrophil-associated inflammatory immune response in afferent lymph and increases antigen uptake by migratory dendritic cells (DCs). Interestingly, antigen positive migratory DCs undergo discordant maturation, with peak expression of CD86 at 4 h and CD80 at 48-72 h post vaccination. Afferent lymph monocytes up-regulate expression of genes related to inflammatory and anti-viral immune phenotypes following vaccination however show no differentiation into APCs prior to their migration to the local lymph node as measured by surface MHC II expression. Finally, this study reveals the addition of poly(I:C) increases systemic antigen-specific humoral immunity. These findings provide a detailed understanding of the real time in vivo immune response induced by liposomes incorporating the innate immune agonist poly(I:C) utilising a vaccination setting comparable to that administered in humans.
authors.affiliation: Biotechnology Research Laboratories, Department of Physiology, Monash University, Wellington Road Clayton VIC 3800, Australia.
authors.forename: Melanie R
authors.initials: MR
authors.lastname: Neeland
authors.affiliation: Zoetis Research and Manufacturing Australia P/L, 45 Poplar Road, Parkville VIC 3052, Australia.
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Elhay
authors.affiliation: Biotechnology Research Laboratories, Department of Physiology, Monash University, Wellington Road Clayton VIC 3800, Australia.
authors.forename: Els N T
authors.initials: EN
authors.lastname: Meeusen
authors.affiliation: Biotechnology Research Laboratories, Department of Physiology, Monash University, Wellington Road Clayton VIC 3800, Australia. Electronic address: michael.deveer@monash.edu.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: de Veer
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D051940:B7-2 Antigen / Q000378:metabolism; D002454:Cell Differentiation; D002465:Cell Movement; D003713:Dendritic Cells / Q000276:immunology*; D007113:Immunity, Innate; D008081:Liposomes / Q000008:administration & dosage; D008196:Lymph / Q000166:cytology*; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology*; D009000:Monocytes / Q000276:immunology; D009504:Neutrophils / Q000276:immunology; D011070:Poly I-C / Q000008:administration & dosage*; D012756:Sheep
chemical_list: D051940:B7-2 Antigen; D008081:Liposomes; D011070:Poly I-C
keywords: Adjuvant; Antigen uptake; Liposomes; Migratory dendritic cells; Monocytes; Poly(I:C); Vaccination