Ishii-Mizuno Y, Umeki Y, Takahashi Y, Kato Y, Takabayashi T, Fujieda S, Takakura Y, Nishikawa M. Nasal delivery of Japanese cedar pollen Cryj1 by using self-gelling immunostimulatory DNA for effective induction of immune responses in mice
Ishii-Mizuno Y, Umeki Y, Takahashi Y, Kato Y, Takabayashi T, Fujieda S, Takakura Y, Nishikawa M. Nasal delivery of Japanese cedar pollen Cryj1 by using self-gelling immunostimulatory DNA for effective induction of immune responses in mice
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Ishii-Mizuno Y、Umeki Y、Takahashi Y、Kato Y、Takabayashi T、Fujieda S、Takakura Y、Nishikawa M。利用自胶凝免疫刺激 DNA 经鼻递送日本雪松花粉 Cryj1，有效诱导小鼠免疫反应
DOI：
10.1016/j.jconrel.2014.12.040
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发表时间：
2015
影响因子：
10.8
通讯作者：
Nishikawa M
中科院分区：
文献类型：
--
作者：
Ishii-Mizuno Y;Umeki Y;Takahashi Y;Kato Y;Takabayashi T;Fujieda S;Takakura Y;Nishikawa M
为了开发一种治疗变应性鼻炎的免疫治疗疫苗，我们开发了一种具有免疫刺激效力的主要日本雪松花粉过敏原Cryj1控释制剂。采用6个寡脱氧核苷酸（odn）制备两组六足类结构DNA (hexapodna)，其中odn具有未甲基化的胞嘧啶-磷酸-鸟嘌呤（CpG）序列（CpG基序），获得免疫刺激DNA水凝胶（sDNA水凝胶）。用不含CpG基序的odn制备非免疫刺激DNA水凝胶（nsDNA水凝胶）。添加到小鼠巨噬细胞样RAW264.7细胞或经鼻给药后，sDNA水凝胶比其组分或nsDNA水凝胶更有效地产生白细胞间素(IL)-12。然后，将含有Cryj1和六足rna的溶液混合制备负载Cryj1的sDNA水凝胶（Cryj1/sDNA水凝胶）配方。Cryj1从sDNA水凝胶中缓慢释放到磷酸盐缓冲盐水中。经鼻给药异硫氰酸荧光素（FITC）标记的Cryj1/sDNA水凝胶小鼠后，FITC-Cryj1在鼻腔内的滞留时间比FITC-Cryj1与六足虫混合溶液的滞留时间更长。用Cryj1/sDNA水凝胶鼻内免疫小鼠，与用其他配方鼻内免疫相比，经Cryj1再刺激后，鼻灌洗液中Cryj1特异性IgG、IL-12和脾脏细胞中干扰素γ的释放水平较高。这些结果表明，自凝胶免疫刺激DNA水凝胶是控制诱导过敏原特异性免疫反应的有效配方。
To develop an immunotherapeutic vaccine for treatment of allergic rhinitis, we developed a controlled release formulation of Cryj1, a major Japanese cedar pollen allergen, with immunostimulatory potency. Two sets of hexapod-like structured DNA (hexapodna) were prepared using six oligodeoxynucleotides (ODNs) each, including ODNs with an unmethylated cytosine–phosphate–guanine (CpG) sequence (CpG motif), to obtain an immunostimulatory DNA hydrogel (sDNA hydrogel). A non-immunostimulatory DNA hydrogel (nsDNA hydrogel) was also prepared using ODNs with no CpG motifs. The sDNA hydrogel was more effective than its components or the nsDNA hydrogel for production of interleukin (IL)-12 after addition to murine macrophage-like RAW264.7 cells or after intranasal administration to mice. Then, a Cryj1-loaded sDNA hydrogel (Cryj1/sDNA hydrogel) formulation was prepared by mixing solutions containing both Cryj1 and hexapodna. Cryj1 was slowly released from the sDNA hydrogel in phosphate-buffed saline. After intranasal administration of the fluorescein isothiocyanate (FITC)-labeled Cryj1/sDNA hydrogel in mice, FITC-Cryj1 was retained in the nasal cavity for a longer period than FITC-Cryj1 mixed with hexapodna in solution. Intranasal immunization of mice with the Cryj1/sDNA hydrogel resulted in high levels of Cryj1-specific IgG in nasal lavage fluid (NFL), IL-12 and interferon-γ release from spleen cells after re-stimulation with Cryj1 when compared with intranasal immunization with the other formulations examined. These results indicate that the self-gelling immunostimulatory DNA hydrogel is an effective formulation for controlled induction of allergen-specific immune responses.