Kitaoka Momoko, Naritomi Ayaka, Hirakawa Yuya, Kamiya Noriho, Goto Masahiro
Department of Applied Chemistry, Graduate School of Engineering, Kyushu University, 744 Moto-oka, 819-0395, Fukuoka, Japan.
Pharm Res. 2015 Apr;32(4):1486-92. doi: 10.1007/s11095-014-1554-5. Epub 2014 Nov 1.
Simple and noninvasive vaccine administration alternatives to injections are desired. A solid-in-oil (S/O) nanodispersion system was able to overcome skin barriers and induce an immune response; however, antibody levels remained low. We applied an immune potentiator, CpG oligodeoxynucleotide (ODN), to enhance the immune response by controlling the T helper 1 (Th1)/T helper 2 (Th2) balance.
S/O nanodispersions containing ovalbumin (OVA) and CpG ODN (CpG-A or CpG-B) were characterized by size distribution analysis and a protein release test. The skin permeation of fluorescence-labeled OVA was observed by fluorescence microscopy. Antigen-specific IgG, IgG1, and IgG2a responses were measured by enzyme-linked immunosorbent assay.
Co-encapsulation of CpG ODNs in S/O nanodispersions enhanced induction of OVA-specific IgG. S/O nanodispersion containing OVA and CpG-A had a smaller mean particle size and permeated the skin more efficiently. In contrast, CpG-B showed the highest protein release and induction of OVA-specific IgG. IgG subclass analysis revealed that OVA induced a Th2-dominant immune response, while the S/O nanodispersion containing CpG-A skewed the immune response toward a Th1-bias.
In combination with CpG ODN, the S/O nanodispersion system efficiently induced an antigen-specific antibody response. The Th1/Th2 immune balance could be controlled by the selection of CpG ODN type.
人们期望有比注射更简单且无创的疫苗接种方式。油包固(S/O)纳米分散体系能够克服皮肤屏障并诱导免疫反应;然而,抗体水平仍然较低。我们应用免疫增强剂CpG寡脱氧核苷酸(ODN),通过控制辅助性T细胞1(Th1)/辅助性T细胞2(Th2)平衡来增强免疫反应。
通过粒径分布分析和蛋白质释放试验对含有卵清蛋白(OVA)和CpG ODN(CpG-A或CpG-B)的S/O纳米分散体进行表征。通过荧光显微镜观察荧光标记的OVA的皮肤渗透情况。采用酶联免疫吸附测定法测量抗原特异性IgG、IgG1和IgG2a反应。
在S/O纳米分散体中共包封CpG ODN可增强OVA特异性IgG的诱导。含有OVA和CpG-A的S/O纳米分散体平均粒径较小,皮肤渗透效率更高。相比之下,CpG-B显示出最高的蛋白质释放率和OVA特异性IgG诱导率。IgG亚类分析显示,OVA诱导了以Th2为主的免疫反应,而含有CpG-A的S/O纳米分散体使免疫反应向Th1偏倚。
与CpG ODN联合使用时,S/O纳米分散体系能有效诱导抗原特异性抗体反应。通过选择CpG ODN类型可控制Th1/Th2免疫平衡。