Cholesteryl Pullulan Encapsulated TNF-αNanoparticles Are an Effective Mucosal Vaccine Adjuvant against Influenza Virus
| Autor: | Mutsuko Taniguchi, Shigeharu Fukuda, Madoka Taniai, Toshio Ariyasu, Daiki Nagatomo, Miho Aga, Tsunetaka Ohta, Harumi Ariyasu |
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| Rok vydání: | 2015 |
| Předmět: |
Cellular immunity
Article Subject Lymphoid Tissue medicine.medical_treatment lcsh:Medicine Biology Antibodies Viral Protective Agents medicine.disease_cause General Biochemistry Genetics and Molecular Biology Proinflammatory cytokine Influenza A Virus H1N1 Subtype Immune system Adjuvants Immunologic Immunity medicine Influenza A virus Animals Humans Particle Size Glucans Cell Proliferation Inflammation Mice Inbred BALB C Mucous Membrane General Immunology and Microbiology Tumor Necrosis Factor-alpha lcsh:R Dendritic Cells General Medicine Gene Expression Regulation Influenza Vaccines Immunology Cancer research Cytokines Nanoparticles Female Immunization Nasal administration Tumor necrosis factor alpha Adjuvant Research Article |
| Zdroj: | BioMed Research International, Vol 2015 (2015) BioMed Research International |
| ISSN: | 2314-6141 2314-6133 |
| DOI: | 10.1155/2015/471468 |
| Popis: | 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 IgG1as 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. |
| Databáze: | OpenAIRE |
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