{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T14:54:43Z","timestamp":1787237683914,"version":"build-2736575974"},"reference-count":40,"publisher":"Wiley","license":[{"start":{"date-parts":[[2015,1,1]],"date-time":"2015-01-01T00:00:00Z","timestamp":1420070400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["BioMed Research International"],"published-print":{"date-parts":[[2015]]},"abstract":"<jats:p>\n                    We encapsulated tumor necrosis factor-\n                    <jats:italic>\u03b1<\/jats:italic>\n                    (TNF-\n                    <jats:italic>\u03b1<\/jats:italic>\n                    ), 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 IgG\n                    <jats:sub>1<\/jats:sub>\n                    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.\n                  <\/jats:p>","DOI":"10.1155\/2015\/471468","type":"journal-article","created":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T17:39:25Z","timestamp":1441129165000},"page":"1-15","source":"Crossref","is-referenced-by-count":46,"title":["Cholesteryl Pullulan Encapsulated TNF-\n                    <i>\u03b1<\/i>\n                    Nanoparticles Are an Effective Mucosal Vaccine Adjuvant against Influenza Virus"],"prefix":"10.1155","volume":"2015","author":[{"given":"Daiki","family":"Nagatomo","sequence":"first","affiliation":[{"name":"R&D Center, Hayashibara Co. 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