title: Comparative activity of biodegradable nanoparticles with aluminum adjuvants: antigen uptake by dendritic cells and induction of immune response in mice.
abstract: Biodegradable poly(γ-glutamic acid) (γ-PGA) nanoparticles (NPs) are considered to be an excellent antigen carrier. Antigen-carrying γ-PGA NPs were examined for their uptake by murine dendritic cells (DCs) and subsequent induction of antigen-specific immune responses in mice and compared with aluminum (AL) adjuvants. Ovalbumin (OVA)-carrying NPs (FITC-OVA-NPs) were taken up much more efficiently by DCs than OVA alone or its AL-associated form. Both OVA-NPs and OVA+AL were detected in an intracellular lysosome compartment of DCs. Furthermore, the uptake of γ-PGA NPs was inhibited in the presence of pinocytosis and phagocytosis inhibitors. Significantly higher induction of antigen-specific CD8(+) T cells was observed in mice immunized with OVA-carrying γ-PGA NPs than in those immunized with OVA alone, OVA+AL, OVA+3-O-desacyl-4'-monophosphoryl lipid A (MPL), and OVA+AL+MPL. Thus, γ-PGA NPs may have great potential as an effective vaccine carrier and adjuvant for clinical use.
authors.affiliation: Division of Antiviral Chemotherapy, Center for Chronic Viral Diseases, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-0544, Japan.
authors.forename: Tomofumi
authors.initials: T
authors.lastname: Uto
authors.forename: Takami
authors.initials: T
authors.lastname: Akagi
authors.forename: Masaaki
authors.initials: M
authors.lastname: Toyama
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Nishi
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Shima
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Akashi
authors.forename: Masanori
authors.initials: M
authors.lastname: Baba
mesh_terms: D020341:Absorbable Implants / Q000706:statistics & numerical data; D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000535:Aluminum / Q000008:administration & dosage*; D000818:Animals; D000941:Antigens / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D004705:Endocytosis / Q000276:immunology; D005260:Female; D007111:Immunity, Cellular; D007114:Immunization; D051379:Mice; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D010047:Ovalbumin / Q000276:immunology / Q000378:metabolism; D011099:Polyglutamic Acid / Q000031:analogs & derivatives / Q000737:chemistry
chemical_list: D000276:Adjuvants, Immunologic; D000941:Antigens; C511775:poly(gamma-glutamic acid); D011099:Polyglutamic Acid; D010047:Ovalbumin; D000535:Aluminum