title: Delivery of antigen using a novel mannosylated dendrimer potentiates immunogenicity in vitro and in vivo.
abstract: Antigen mannosylation has been shown to be an effective approach to potentiate antigen immunogenicity, due to the enhanced antigen uptake and presentation by APC. To overcome disadvantages associated with conventional methods used to mannosylate antigens, we have developed a novel mannose-based antigen delivery system that utilizes a polyamidoamine (PAMAM) dendrimer. It is demonstrated that mannosylated dendrimer ovalbumin (MDO) is a potent immune inducer. With a strong binding avidity to DC, MDO potently induced OVA-specific T cell response in vitro. It was found that the immunogenicity of MDO was due not only to enhanced antigen presentation, but also to induction of DC maturation. Mice immunized with MDO generated strong OVA-specific CD4(+)/CD8(+) T cell and antibody responses. MDO also targeted lymph node DC to cross-present OVA, leading to OTI CD8(+) T cell proliferation. Moreover, upon challenge with B16-OVA tumor cells, tumors in mice pre-immunized with MDO either did not grow or displayed a much more delayed onset, and had slower kinetics of growth than those of OVA-immunized mice. This mannose-based antigen delivery system was applied here for the first time to the immunization study. With several advantages and exceptional adjuvanticity, we propose mannosylated dendrimer as a potential vaccine carrier.
authors.affiliation: Immunology and Vaccine Laboratory, Burnet Institute, Melbourne, Australia.
authors.forename: Kuo-Ching
authors.initials: KC
authors.lastname: Sheng
authors.forename: Martha
authors.initials: M
authors.lastname: Kalkanidis
authors.forename: Dodie S
authors.initials: DS
authors.lastname: Pouniotis
authors.forename: Sandra
authors.initials: S
authors.lastname: Esparon
authors.forename: Choon Kit
authors.initials: CK
authors.lastname: Tang
authors.forename: Vasso
authors.initials: V
authors.lastname: Apostolopoulos
authors.forename: Geoffrey A
authors.initials: GA
authors.lastname: Pietersz
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D000941:Antigens / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology*; D002478:Cells, Cultured; D050091:Dendrimers / Q000008:administration & dosage* / Q000737:chemistry*; D003713:Dendritic Cells / Q000276:immunology; D016503:Drug Delivery Systems; D004527:Egg Proteins / Q000008:administration & dosage / Q000276:immunology; D008358:Mannose / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D008546:Melanoma, Experimental / Q000276:immunology / Q000517:prevention & control; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D010446:Peptide Fragments; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000941:Antigens; D050091:Dendrimers; D004527:Egg Proteins; C110366:OVA-8; D010446:Peptide Fragments; D010047:Ovalbumin; D008358:Mannose