中文摘要：研究分析了壳聚糖衍生物磷酸化壳聚糖（PCS）作为免疫佐剂的功能。PCS对酸碱度敏感，在pH 7.0 以下时可溶于水，pH高于7.0 时则变成胶状。根据PCS这一特性，试验制备了含卵清蛋白的中性PCS水溶液（OVA），将该水溶液通过肌肉直接注射到小鼠体内，并通过OVA免疫形成了包含OVA的胶状网络。结果表明：采用浓度为30mg/ML的PCS水凝胶作为疫苗传递系统可以提高抗原特异性反应，包括提高抗原特异性IgG抗体、脾细胞分泌的IFN-和IL-4浓度，以及记忆性CD4(+) 和 CD8(+) T细胞浓度。体外成像和免疫组化结果表明，PCS凝胶网络可以控制抗原的释放速度，从而提高免疫效率，延长抗原对免疫系统的刺激。因此，PCS可以作为疫苗传递系统应用于免疫治疗。
外文摘要： In the field of immunotherapy, immune vaccinations have received more and more attention for disease prevention and treatment. In immune vaccination, efficient vaccine adjuvants are necessary due to the weak immunogenicity of vaccines. Some traditional vaccine adjuvants have been widely used but have shown obvious limitations such as poor biosafety. Therefore, researchers make a great effort to develop more functional novel immune adjuvants such as chitosan-based immune adjuvants. However, chitosan is poorly water soluble, which greatly limits its application as immune adjuvants, regardless of its good biocompatibility, biodegradability, and other biological activities. In this work, we prepared a water-soluble chitosan derivative phosphorylated chitosan (PCS) and evaluated its potential as a novel immune adjuvant. PCS was found to be pH sensitive: specifically, it was water soluble at pH<7.0 but began to gel at pH >7.0. By virtue of this, neutral PCS aqueous solutions containing ovalbumin (OVA) antigen was intramuscularly injected into test mice, which would transform to an OVA-containing gel network for OVA immunization. The results showed that the use of 30mg/mL PCS-based hydrogel as vaccine delivery system contributed to significantly higher level of antigen-specific immune responses, including higher level of antigen-specific IgG antibodies, IFN- and IL-4 cytokines secretion by splenocytes, as well as memory CD4(+) and CD8(+) T cells. Invivo imaging and immunohistochemistry assays suggest that the improved immunization efficacy may be attributed to the controlled release of antigen from injection site by PCS gel network, and then prolonged antigen stimuli to the immune system. From the results, PCS could be developed as a promising vaccine delivery system for immunotherapy.
外文关键词： Phosphorylated chitosan； immune vaccination； vaccine delivery system
作者：Wei, JY; Xue, W; Yu, XF; Qiu, XZ; Liu, ZH
作者单位：暨南大学
期刊名称：JOURNAL OF BIOMATERIALS APPLICATIONS
期刊影响因子：1.988
出版年份：2017
出版刊次：10
点击下载：pH敏感磷酸化壳聚糖水凝胶可作为疫苗传递系统用于肌肉内免疫