title: Mucosal vaccination using claudin-4-targeting.
abstract: Mucosa-associated lymphoid tissue (MALT) plays pivotal roles in mucosal immune responses. Efficient delivery of antigens to MALT is a critical issue for the development of mucosal vaccines. Although claudin-4 is preferentially expressed in MALT in the gut, a claudin-4-targeting approach for mucosal vaccination has never been developed. In the present study, we found that claudin-4 is expressed in nasal MALT, and we prepared a fusion protein of ovalbumin (OVA) as a model antigen with a claudin-4-binder, the C-terminal fragment of Clostridium perfringens enterotoxin (C-CPE) (OVA-C-CPE). Nasal immunization with OVA-C-CPE, but not a mixture of OVA and C-CPE, induced the production of OVA-specific serum IgG and nasal, vaginal and fecal IgA. Deletion of the claudin-4-binding region in OVA-C-CPE attenuated the induction of the immune responses. OVA-C-CPE immunization activated both Th1 and Th2 responses, and nasal immunization with OVA-C-CPE showed anti-tumor activity in mice inoculated with OVA-expressing thymoma cells. These results indicate that the claudin-4-targeting may be a potent strategy for nasal vaccination.
authors.affiliation: Laboratory of Bio-Functional Molecular Chemistry, Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Kakutani
authors.forename: Masuo
authors.initials: M
authors.lastname: Kondoh
authors.forename: Masahiro
authors.initials: M
authors.lastname: Fukasaka
authors.forename: Hidehiko
authors.initials: H
authors.lastname: Suzuki
authors.forename: Takao
authors.initials: T
authors.lastname: Hamakubo
authors.forename: Kiyohito
authors.initials: K
authors.lastname: Yagi
mesh_terms: D000818:Animals; D019496:Cancer Vaccines / Q000276:immunology; D045744:Cell Line, Tumor; D062506:Claudin-4; D004768:Enterotoxins / Q000737:chemistry / Q000276:immunology; D005260:Female; D005786:Gene Expression Regulation; D056724:Immunity, Humoral / Q000276:immunology; D018928:Immunity, Mucosal / Q000276:immunology*; D008221:Lymphoid Tissue / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009297:Nasal Mucosa / Q000276:immunology*; D009305:Nasopharynx / Q000378:metabolism; D010047:Ovalbumin / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D013945:Thymoma / Q000276:immunology; D014611:Vaccination
chemical_list: D019496:Cancer Vaccines; D062506:Claudin-4; C568158:Cldn4 protein, mouse; D004768:Enterotoxins; D008565:Membrane Proteins; C035598:enterotoxin, Clostridium; D010047:Ovalbumin