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针对表达猪带绦虫囊尾蚴抗原 TSOL18 的重组减毒鼠伤寒沙门氏菌菌株的免疫反应。

Immune responses to a recombinant attenuated Salmonella typhimurium strain expressing a Taenia solium oncosphere antigen TSOL18.

机构信息

State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, CAAS, Yanchangbu, Gansu, China.

出版信息

Comp Immunol Microbiol Infect Dis. 2013 Jan;36(1):17-23. doi: 10.1016/j.cimid.2012.09.006. Epub 2012 Dec 6.

Abstract

A tapeworm, Taenia solium, remains a great threat to human health, particularly in developing countries. The life cycle of T. solium is thought to be terminated via vaccination of intermediate hosts. In this study, we constructed a recombinant attenuated Salmonella typhimurium live vaccine strain χ4558 expressing a TSOL18 antigen. SDS-PAGE and Western blot confirmed the expression of the interest protein and its antigenic property. The recombinant strain stably propagated in vitro, of which the growth was not reversely influenced by TSOL18 protein expressed. It was also shown that mice survived 10(12) CFU of S. typhimurium χ4558, while all mice infected with 10(7) CFU of the wild-type died within five days. The mouse experiment indicated that vaccine strain χ4558 induced a high titer of specific antibody for a long time. In contrast to the controls, the vaccinated mice had an obvious augment of CD4(+) and CD8(+) T lymphocytes and the percentage of helper CD4(+)/CD8(+) T lymphocytes was significantly increased (p<0.01). After oral administration, S. typhimurium χ4558 was first colonized mainly in the Peyer's patches and then predominantly in the mesenteric lymph nodes and spleens in the vaccinated mice. In addition, the high levels of specific anti-TSOL18 antibodies were also observed in pigs administrated with S. typhimurium χ4558. Collectively, these results demonstrate the possibility of use of an attenuated S. typhimurium strain as a vector to deliver protective antigens of T. solium.

摘要

猪带绦虫,即猪肉绦虫,仍然对人类健康构成巨大威胁,尤其是在发展中国家。猪带绦虫的生命周期被认为是通过中间宿主的疫苗接种来终止的。在这项研究中,我们构建了一株表达 TSOL18 抗原的重组减毒鼠伤寒沙门氏菌活疫苗株 χ4558。SDS-PAGE 和 Western blot 证实了目的蛋白的表达及其抗原特性。重组菌株在体外稳定增殖,其生长不受表达的 TSOL18 蛋白的影响。结果还表明,小鼠在感染 10(12)CFU 的鼠伤寒沙门氏菌 χ4558 后存活下来,而所有感染 10(7)CFU 野生型的小鼠在五天内全部死亡。小鼠实验表明,疫苗株 χ4558 可诱导长时间高滴度的特异性抗体。与对照组相比,接种疫苗的小鼠 CD4(+)和 CD8(+)T 淋巴细胞明显增加,辅助性 CD4(+)/CD8(+)T 淋巴细胞的比例显著增加(p<0.01)。口服给药后,鼠伤寒沙门氏菌 χ4558 主要定植于派尔集合淋巴结,然后主要定植于肠系膜淋巴结和接种疫苗的小鼠脾脏。此外,在给予鼠伤寒沙门氏菌 χ4558 的猪中也观察到高水平的特异性抗 TSOL18 抗体。综上所述,这些结果表明,减毒鼠伤寒沙门氏菌菌株可作为载体传递猪带绦虫保护性抗原。

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