title: Positively charged liposome functions as an efficient immunoadjuvant in inducing cell-mediated immune response to soluble proteins.
abstract: In order to design an optimized liposome immunoadjuvant for inducing cell-mediated immune response against soluble proteinaceous antigens, we investigated the effect of liposomal surface charge on the immunoadjuvant action. Positively charged liposomes containing soluble antigens functioned as a more potent inducer of antigen-specific cytotoxic T lymphocyte responses and delayed type hypersensitivity response than negatively charged and neutral liposomes containing the same concentrations of antigens. To clarify the reason of the differential immune response, we examined the delivery of soluble proteins by the liposomes into the cytoplasm of macrophages, using fragment A of diphtheria toxin (DTA) as a marker. We found that positively charged liposomes encapsulating DTA are cytotoxic to macrophages, while empty positively charged liposomes, DTA in negatively charged and neutral liposomes are not. Consistent with this, only macrophages pulsed with OVA in positively charged liposomes could significantly stimulate OVA-specific, class I MHC-restricted T cell hybridoma. These results suggest that the positively charged liposomes can deliver proteinaceous antigens efficiently into the cytoplasm of the macrophages/antigen-presenting cells, where the antigens are processed to be presented by class I MHC molecules to induce the cell-mediated immune response. Possible development of the safe and effective vaccine is discussed.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Osaka University, 1-6, Yamadaoka, Suita, Osaka, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Nakanishi
authors.forename: J
authors.initials: J
authors.lastname: Kunisawa
authors.forename: A
authors.initials: A
authors.lastname: Hayashi
authors.forename: Y
authors.initials: Y
authors.lastname: Tsutsumi
authors.forename: K
authors.initials: K
authors.lastname: Kubo
authors.forename: S
authors.initials: S
authors.lastname: Nakagawa
authors.forename: M
authors.initials: M
authors.lastname: Nakanishi
authors.forename: K
authors.initials: K
authors.lastname: Tanaka
authors.forename: T
authors.initials: T
authors.lastname: Mayumi
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D017951:Antigen Presentation; D005260:Female; D008081:Liposomes / Q000008:administration & dosage*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D008081:Liposomes; D010047:Ovalbumin