Cholesteryl Pullulan Encapsulated TNF-α Nanoparticles Are an Effective Mucosal Vaccine Adjuvant against Influenza Virus.
Cholesteryl Pullulan Encapsulated TNF-α Nanoparticles Are an Effective Mucosal Vaccine Adjuvant against Influenza Virus.
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DOI：
10.1155/2015/471468
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发表时间：
2015
影响因子：
--
通讯作者：
Fukuda S
中科院分区：
文献类型：
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作者：
Nagatomo D;Taniai M;Ariyasu H;Taniguchi M;Aga M;Ariyasu T;Ohta T;Fukuda S
以胆固醇普鲁兰多糖（cholesterylpullulan，CHP）为载体，制备了肿瘤坏死因子-α（tumor necrosis factor-α，TNF-α）/CHP纳米粒。在这份报告中，我们描述了免疫增强能力的纳米粒子作为疫苗佐剂。TNF/CHP纳米粒显示出优异的储存稳定性和增强宿主对外部免疫原的免疫应答。纳米颗粒是有效的，通过鼻腔给药途径诱导全身IgG 1以及粘膜伊加。我们将纳米颗粒应用于实验性流感病毒感染模型中，以研究其佐剂能力。TNF/CHP纳米颗粒与常规裂解疫苗组合通过鼻腔给药保护小鼠免受A/PR/8/34（H1N1）流感病毒的致命攻击。机制研究表明，纳米颗粒增强树突状细胞（DC）的抗原摄取，并适度诱导鼻咽淋巴组织（NALT）中炎症相关基因的表达，导致B和T细胞的激活。初步安全性研究显示TNF/CHP纳米粒无严重毒性。仅在重复给药中观察到对鼻粘膜的轻度至中度影响，并且这些影响似乎是可逆的。我们的数据表明，TNF/CHP纳米颗粒有效地增强体液和细胞免疫，并且可能成为对抗传染病（特别是粘膜传染病）的疫苗的潜在佐剂。
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.