pH-Sensitive fusogenic polymer-modified liposomes as a carrier of antigenic proteins for activation of cellular immunity.
By modification of liposomes with poly(glycidol) derivatives such as succinylated poly(glycidol) and 3-methylglutarylated poly(glycidol), we have developed functional liposomes that generate fusion ability at mildly acidic pH. We investigated the feasibility of these polymer-modified liposomes as a carrier of antigenic proteins for induction of cellular immunity. These pH-sensitive fusogenic liposomes encapsulating ovalbumin (OVA) were applied to DC2.4 cells, a murine dendritic cell line. Observation with confocal laser scanning microscopy showed that these polymer-modified liposomes were taken up efficiently by the cells, thereafter delivering their contents into the cytosol, probably through fusion with endosomal membranes. Murine bone marrow-derived dendritic cells treated with polymer-modified liposomes encapsulating OVA stimulated CD8-OVA1.3 cells more strongly than OT4H.1D5 cells, indicating that the liposomes induced MHC class I-restricted presentation. Furthermore, administration of the polymer-modified, OVA-loaded liposomes from nasal cavities of mice induced stronger cellular immune responses than the OVA-loaded plain liposomes. Because the ability of the polymer-modified liposomes to activate cellular immunity was comparable to that of Freund's complete adjuvant, which is a widely used adjuvant, they potentially have use in production of efficient vaccines for immunotherapy.
Department of Applied Chemistry, Osaka Prefecture University, Gakuen-cho, Naka-ku, Sakai, Japan.
Eiji
E
Yuba
Chie
C
Kojima
Atsushi
A
Harada
Tana
Shinobu
S
Watarai
Kenji
K
Kono
D000818:Animals; D000941:Antigens / Q000008:administration & dosage* / Q000737:chemistry; D002460:Cell Line; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D006863:Hydrogen-Ion Concentration; D007113:Immunity, Innate / Q000187:drug effects / Q000276:immunology*; D008081:Liposomes / Q000737:chemistry*; D008422:Materials Testing; D051379:Mice; D010047:Ovalbumin / Q000008:administration & dosage* / Q000737:chemistry
D000941:Antigens; D008081:Liposomes; D010047:Ovalbumin