title: Cholesteryl Pullulan Encapsulated TNF-α Nanoparticles Are an Effective Mucosal Vaccine Adjuvant against Influenza Virus.
abstract: We encapsulated tumor necrosis factor-α (TNF-α), a major proinflammatory cytokine, into cholesteryl pullulan (CHP) to prepare TNF/CHP nanoparticles. In this report, we describe the immune-enhancing capability of the nanoparticles to act as a vaccine adjuvant. TNF/CHP nanoparticles showed excellent storage stability and enhanced host immune responses to external immunogens. The nanoparticles were effective via the nasal route of administration for inducing systemic IgG1 as well as mucosal IgA. We applied the nanoparticles in a model experimental influenza virus infection to investigate their adjuvant ability. TNF/CHP nanoparticles combined with a conventional split vaccine protected mice via nasal administration against a lethal challenge of A/PR/8/34 (H1N1) influenza virus. Mechanistic studies showed that the nanoparticles enhanced antigen uptake by dendritic cells (DCs) and moderately induced the expression of inflammation-related genes in nasopharynx lymphoid tissue (NALT), leading to the activation of both B and T cells. Preliminary safety study revealed no severe toxicity to TNF/CHP nanoparticles. Slight-to-moderate influences in nasal mucosa were observed only in the repeated administration and they seemed to be reversible. Our data show that TNF/CHP nanoparticles effectively enhance both humoral and cellular immunity and could be a potential adjuvant for vaccines against infectious diseases, especially in the mucosa.
authors.affiliation: R&D Center, Hayashibara Co. Ltd., 675-1 Fujisaki, Naka-ku, Okayama 702-8006, Japan.
authors.forename: Daiki
authors.initials: D
authors.lastname: Nagatomo
authors.affiliation: R&D Center, Hayashibara Co. Ltd., 675-1 Fujisaki, Naka-ku, Okayama 702-8006, Japan.
authors.forename: Madoka
authors.initials: M
authors.lastname: Taniai
authors.affiliation: R&D Center, Hayashibara Co. Ltd., 675-1 Fujisaki, Naka-ku, Okayama 702-8006, Japan.
authors.forename: Harumi
authors.initials: H
authors.lastname: Ariyasu
authors.affiliation: R&D Center, Hayashibara Co. Ltd., 675-1 Fujisaki, Naka-ku, Okayama 702-8006, Japan.
authors.forename: Mutsuko
authors.initials: M
authors.lastname: Taniguchi
authors.affiliation: R&D Center, Hayashibara Co. Ltd., 675-1 Fujisaki, Naka-ku, Okayama 702-8006, Japan.
authors.forename: Miho
authors.initials: M
authors.lastname: Aga
authors.affiliation: R&D Center, Hayashibara Co. Ltd., 675-1 Fujisaki, Naka-ku, Okayama 702-8006, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Ariyasu
authors.affiliation: R&D Center, Hayashibara Co. Ltd., 675-1 Fujisaki, Naka-ku, Okayama 702-8006, Japan.
authors.forename: Tsunetaka
authors.initials: T
authors.lastname: Ohta
authors.affiliation: R&D Center, Hayashibara Co. Ltd., 675-1 Fujisaki, Naka-ku, Okayama 702-8006, Japan.
authors.forename: Shigeharu
authors.initials: S
authors.lastname: Fukuda
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000187:drug effects; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D005936:Glucans / Q000494:pharmacology*; D006801:Humans; D007109:Immunity / Q000187:drug effects; D007114:Immunization; D007249:Inflammation / Q000473:pathology; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects*; D007252:Influenza Vaccines / Q000276:immunology*; D008221:Lymphoid Tissue / Q000187:drug effects / Q000473:pathology / Q000821:virology; D008807:Mice, Inbred BALB C; D009092:Mucous Membrane / Q000187:drug effects / Q000276:immunology*; D053758:Nanoparticles / Q000008:administration & dosage*; D010316:Particle Size; D020011:Protective Agents / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D016207:Cytokines; D005936:Glucans; D007252:Influenza Vaccines; D020011:Protective Agents; D014409:Tumor Necrosis Factor-alpha; C009109:pullulan