title: Cell-penetrating peptide-linked polymers as carriers for mucosal vaccine delivery.
abstract: We evaluated the potential of poly(N-vinylacetamide-co-acrylic acid) modified with d-octaarginine, which is a typical cell-penetrating peptide, as a carrier for mucosal vaccine delivery. Mice were nasally inoculated four times every seventh day with PBS containing ovalbumin with or without the d-octaarginine-linked polymer. The polymer enhanced the production of ovalbumin-specific immunoglobulin G (IgG) and secreted immunoglobulin A (IgA) in the serum and the nasal cavity, respectively. Ovalbumin internalized into nasal epithelial cells appeared to stimulate IgA production. Ovalbumin transferred to systemic circulation possibly enhanced IgG production. An equivalent dose of the cholera toxin B subunit (CTB), which was used as a positive control, was superior to the polymer in enhancing antibody production; however, dose escalation of the polymer overcame this disadvantage. A similar immunization profile was also observed when ovalbumin was replaced with influenza virus HA vaccines. The polymer induced a vaccine-specific immune response identical to that induced by CTB, irrespective of the antibody type, when its dose was 10 times that of CTB. Our cell-penetrating peptide-linked polymer is a potential candidate for antigen carriers that induce humoral immunity on the mucosal surface and in systemic circulation when nasally coadministered with antigens.
authors.affiliation: Faculty of Pharmaceutical Sciences, Setsunan University , 45-1 Nagaotoge-cho, Hirakata, Osaka, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Sakuma
authors.forename: Masaya
authors.initials: M
authors.lastname: Suita
authors.forename: Saki
authors.initials: S
authors.lastname: Inoue
authors.forename: Yoko
authors.initials: Y
authors.lastname: Marui
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Nishida
authors.forename: Yoshie
authors.initials: Y
authors.lastname: Masaoka
authors.forename: Makoto
authors.initials: M
authors.lastname: Kataoka
authors.forename: Shinji
authors.initials: S
authors.lastname: Yamashita
authors.forename: Noriko
authors.initials: N
authors.lastname: Nakajima
authors.forename: Norihiro
authors.initials: N
authors.lastname: Shinkai
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Yamauchi
authors.forename: Ken-ichiro
authors.initials: K
authors.lastname: Hiwatari
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tachikawa
authors.forename: Ryoji
authors.initials: R
authors.lastname: Kimura
authors.forename: Tomofumi
authors.initials: T
authors.lastname: Uto
authors.forename: Masanori
authors.initials: M
authors.lastname: Baba
mesh_terms: D000081:Acetamides / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology; D000179:Acrylates / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology; D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000737:chemistry; D000281:Administration, Intranasal / Q000379:methods; D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D000941:Antigens / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology; D057846:Cell-Penetrating Peptides / Q000008:administration & dosage* / Q000737:chemistry / Q000276:immunology; D002772:Cholera Toxin / Q000276:immunology; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods; D004847:Epithelial Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D005260:Female; D056724:Immunity, Humoral / Q000276:immunology; D007071:Immunoglobulin A, Secretory / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009092:Mucous Membrane / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D009297:Nasal Mucosa / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D010047:Ovalbumin / Q000276:immunology; D019999:Pharmaceutical Solutions / Q000008:administration & dosage / Q000737:chemistry; D011108:Polymers / Q000008:administration & dosage* / Q000737:chemistry; D011145:Polyvinyls / Q000008:administration & dosage / Q000737:chemistry; D014611:Vaccination / Q000379:methods; D014612:Vaccines / Q000008:administration & dosage* / Q000737:chemistry
chemical_list: D000081:Acetamides; D000179:Acrylates; D000276:Adjuvants, Immunologic; D000941:Antigens; D057846:Cell-Penetrating Peptides; D004337:Drug Carriers; D007071:Immunoglobulin A, Secretory; D007074:Immunoglobulin G; D007252:Influenza Vaccines; D019999:Pharmaceutical Solutions; D011108:Polymers; D011145:Polyvinyls; D014612:Vaccines; C539745:poly(N-vinylacetamide); D010047:Ovalbumin; D002772:Cholera Toxin; C036658:acrylic acid