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评估对表达丝氨酸蛋白酶抑制剂 3 的孢子的免疫反应。

Evaluation of immune response to spores expressing serpin3.

机构信息

Department of Parasitology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou510080, People's Republic of China.

Key Laboratory for Tropical Diseases Control, Ministry of Education, Sun Yat-Sen University, Guangzhou510080, People's Republic of China.

出版信息

Parasitology. 2020 Sep;147(10):1080-1087. doi: 10.1017/S0031182020000797. Epub 2020 May 14.

Abstract

Clonorchis sinensis (C. sinensis) is one of the most serious food-borne parasites, which can lead to liver fibrosis or cholangiocarcinoma. Effective measures for clonorchiasis prevention are still urgently needed. Bacillus subtilis (B. subtilis) is an effective antigen delivery platform for oral vaccines. Chonorchis sinensis serpin (CsSerpin) was proved to be potential vaccine candidates. In this study, CsSerpin3 was displayed on the surface of B. subtilis spore and recombinant spores were orally administrated to BALB/C mice. CsSerpin3-specific IgA levels in faecal, bile and intestinal mucous increased at 4-8 weeks after the first administration compared with those in control groups. The mucus production and the number of goblet cells in intestinal mucosa elevated in B.s-CotC-CsSerpin3 (CotC, coat protein of B. subtilis spore) spores treated group compared to those in blank control. No significant difference in the activities of glutamic-pyruvic transaminase/ alanine aminotransferase and glutamic oxalacetic transaminase/aspartate aminotransferase were observed between groups. There was no side effect inflammation and observable pathological damage in the liver tissue of mice after administration. Moreover, collagen deposition and Ishak score were statistically reduced in B.s-CotC-CsSerpin3 spores treated mice. In conclusion, B. subtilis spores displaying CsSerpin3 could be investigated further as an oral vaccine against clonorchiasis.

摘要

华支睾吸虫(C. sinensis)是最严重的食源性寄生虫之一,可导致肝纤维化或胆管癌。仍然迫切需要有效的华支睾吸虫病预防措施。枯草芽孢杆菌(B. subtilis)是口服疫苗的有效抗原递送平台。华支睾吸虫丝氨酸蛋白酶抑制剂(CsSerpin)已被证明是潜在的疫苗候选物。在这项研究中,CsSerpin3 被展示在枯草芽孢杆菌孢子的表面上,并口服给予 BALB/C 小鼠重组孢子。与对照组相比,首次给药后 4-8 周,粪便、胆汁和肠粘液中的 CsSerpin3 特异性 IgA 水平增加。与空白对照组相比,B.s-CotC-CsSerpin3(CotC,枯草芽孢杆菌孢子的外壳蛋白)孢子处理组的粘液产生和肠粘膜中杯状细胞的数量增加。各组间谷氨酸-丙酮酸转氨酶/丙氨酸转氨酶和谷氨酸草酰乙酸转氨酶/天冬氨酸转氨酶的活性无显著差异。给药后,小鼠肝组织无炎症和可观察到的病理损伤。此外,B.s-CotC-CsSerpin3 孢子处理组的胶原沉积和 Ishak 评分均有统计学降低。总之,展示 CsSerpin3 的枯草芽孢杆菌孢子可进一步作为抗华支睾吸虫病的口服疫苗进行研究。

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