中文摘要：本研究表明pH敏感的可降解碳酸磷灰石（CA）纳米颗粒作为CpG ODN的传递系统，可以增加I 型干扰素（如IFN-α）的浓度，提高CpG ODN的佐剂效应。与CpG ODN相比，包含CpG ODN的碳酸磷灰石纳米颗粒（CA-CpG）能够显著提高小鼠树突状细胞和人外周血单核细胞中IFN-α的浓度，且CA-CpG处理组诱导产生的IL-12、IFN-g的浓度显著高于CpG ODN处理组；此外，CA-CpG处理组引流淋巴结中的细胞因子浓度更高。当CA-CpG与卵清蛋白、流感病毒血凝素等抗原一起免疫时能够激发机体产生更高浓度的抗原特异性免疫反应和CD8(+)细胞毒性T淋巴细胞反应；CA-CpG传递的禽流感疫苗的效率要高于CpG ODNs的佐剂效率。这些结果表明，CA作为CpG ODNs的传递系统能够提高IFN-α等细胞因子的浓度，提高CpG ODNs的佐剂效率。
 
外文摘要：Vaccine adjuvants that can induce not only antigen-specific antibody responses but also Th1-type immune responses and CD8(+) cytotoxic T lymphocyte responses are needed for the development of vaccines against infectious diseases and cancer. Of many available adjuvants, oligodeoxynucleotides (ODNs) with unmethylated cytosine-phosphate-guanine (CpG) motifs are the most promising for inducing the necessary immune responses, and these adjuvants are currently under clinical trials in humans. However, the development of novel delivery vehicles that enhance the adjuvant effects of CpG ODNs, subsequently increasing the production of cytokines such as type-I interferons (IFNs), is highly desirable. In this study, we demonstrate the potential of pH-responsive biodegradable carbonate apatite (CA) nanoparticles as CpG ODN delivery vehicles that can enhance the production of type-I IFNs (such as IFN-alpha) relative to that induced by CpG ODNs and can augment the adjuvant effects of CpG ODNs in vivo. In contrast to CpG ODNs, CA nanoparticles containing CpG ODNs (designated CA-CpG) induced significant IFN-alpha production by mouse dendritic cells and human peripheral blood mononuclear cells in vitro; and production of interleukin-12, and IFN-gamma was higher in CA-CpG-treated groups than in CpG ODNs groups. In addition, treatment with CA-CpG resulted in higher cytokine production in draining lymph nodes than did treatment with CpG ODNs in vivo. Furthermore, vaccination with CA-CpG plus an antigen, such as ovalbumin or influenza virus hemagglutinin, resulted in higher antigen-specific antibody responses and CD8(+) cytotoxic T lymphocyte responses in vivo, in an interleukin-12- and type-I IFN-dependent manner, than did vaccination with the antigen plus CpG ODNs; in addition, the efficacy of the vaccine against influenza virus was higher with CA-CpG as the adjuvant than with CpG ODNs as the adjuvant. These data show the potential of CA nanoparticles to serve as CpG ODN delivery vehicles that increase the production of cytokines, especially IFN-alpha, induced by CpG ODNs and thus augment the efficacy of CpG ODNs as adjuvants. We expect that the strategy reported herein will facilitate the design and development of novel adjuvant delivery vehicles for vaccines.
外文关键词：adjuvant, cytosine-phosphate-guanine oligodeoxynucleotide, influenza virus, interferon-alpha, nanoparticle, vaccine
作者：Takahashi, H; Misato, K; Aoshi, T; Yamamoto, Y; Kubota, Y; Wu, X; Kuroda, E; Ishii, KJ; Yamamoto, H; Yoshioka, Y
作者单位：日本大阪大学
期刊名称：FRONTIERS IN IMMUNOLOGY
期刊影响因子：6.43
出版年份：2018
出版刊次：4
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