Uchida Masaki, Natsume Hideshi, Kishino Tohru, Seki Toshinobu, Ogihara Masahiko, Juni Kazuhiko, Kimura Masayuki, Morimoto Yasunori
Faculty of Pharmaceutical Sciences, Josai University, Sakado, Saitama 350-0295, Japan.
Vaccine. 2006 Mar 15;24(12):2120-30. doi: 10.1016/j.vaccine.2005.11.027. Epub 2005 Nov 28.
In the present study, we investigated whether poly-(DL-lactide-co-glycolide) (50:50) microspheres (PLG MS) containing a model antigen, ovalbumin (OVA), were delivered into mouse skin and the immune responses induced using a microparticulate bombardment system, Helios gene gun system, which can painlessly deliver the powdered drug through the stratum corneum to the epidermal-dermal interface using a high velocity supersonic flow of helium gas to accelerate the particles. The introduction of OVA-loaded PLG MS shows helium pressure-dependence, so that improved introduction can be achieved by a higher helium pressure used, thereby inducing sufficient anti-OVA IgG level. Moreover, in order to determine the type of immune system induced using particle bombardment, we investigated helper T-cell response characterized by the cytokine production in the isolated splenocytes 6 weeks after immunization and consequent production of the anti-OVA IgG subclasses in the serum in mice. As a result, IL-4 production in splenocytes and anti-OVA IgG1 level were preferentially elicited by particle bombardment with OVA-loaded PLG MS compared with IFN-gamma and anti-OVA IgG2a level. It seemed likely that particle bombardment using this system led to a Th-2 type immune response, i.e. a humoral immune response. In conclusion, this microparticulate bombardment system is a promising immunization method, expected to become an alternative to needle injection used to administer a broad range of vaccines for the treatment of various diseases.
在本研究中,我们调查了含有模型抗原卵清蛋白(OVA)的聚(DL-丙交酯-共-乙交酯)(50:50)微球(PLG MS)是否能通过微粒轰击系统(Helios基因枪系统)递送至小鼠皮肤,并诱导免疫反应。该系统可利用高速超音速氦气流加速颗粒,将粉末状药物无痛地透过角质层递送至表皮-真皮界面。负载OVA的PLG MS的导入显示出对氦气压力的依赖性,因此使用更高的氦气压力可实现更好的导入效果,从而诱导出足够的抗OVA IgG水平。此外,为了确定使用颗粒轰击诱导的免疫系统类型,我们在免疫6周后,研究了分离的脾细胞中以细胞因子产生为特征的辅助性T细胞反应,以及小鼠血清中随后产生的抗OVA IgG亚类。结果,与IFN-γ和抗OVA IgG2a水平相比,负载OVA的PLG MS颗粒轰击优先诱导脾细胞产生IL-4和抗OVA IgG1水平。使用该系统进行颗粒轰击似乎会导致Th-2型免疫反应,即体液免疫反应。总之,这种微粒轰击系统是一种有前景的免疫方法,有望成为用于治疗各种疾病的多种疫苗注射给药时的针剂注射替代方法。