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经减毒鼠伤寒沙门氏菌传递的 Ts87 DNA 疫苗口服免疫可引发针对旋毛虫幼虫攻击的保护性免疫应答。

Oral vaccination with Ts87 DNA vaccine delivered by attenuated Salmonella typhimurium elicits a protective immune response against Trichinella spiralis larval challenge.

机构信息

Department of Parasitology, School of Basic Medical Sciences, Capital Medical University, 10 Xitoutiao, You An Men, Beijing 100069, China.

出版信息

Vaccine. 2010 Mar 24;28(15):2735-42. doi: 10.1016/j.vaccine.2010.01.026. Epub 2010 Jan 25.

Abstract

We have previously reported that Ts87 is an immunodominant antigen that induces protective immunity against Trichinella spiralis larval challenge. In this study, the Ts87 gene was cloned into an expression plasmid, pVAX1, and the recombinant Ts87 DNA was transformed into attenuated Salmonella typhimurium strain SL7207. Oral immunization of mice with Ts87 DNA delivered in S. typhimurium elicited a significant local mucosal IgA response and a systemic Th1/Th2 immune response. Cytokine profiling also showed a significant increase in the Th1 (IFN-gamma) and Th2 (IL-5, 6, 10) responses in splenocytes of immunized mice upon stimulation with Ts87 antigen. An immunofluorescence assay performed with antisera revealed that the recombinant Ts87 protein was expressed in mesenteric lymph nodes of immunized mice. The mice immunized with Salmonella-delivered Ts87 DNA displayed a statistically significant 29.8% reduction in adult worm burden and a 34.2% reduction in muscle larvae following challenge with T. spiralis larvae, compared with mice immunized with empty Salmonella or a PBS control. Our results demonstrate that Ts87 DNA delivered by attenuated live S. typhimurium elicits a local IgA response and a balanced Th1/Th2 immune response and produces partial protection against T. spiralis infection in mice.

摘要

我们之前曾报道过 Ts87 是一种免疫优势抗原,可诱导针对旋毛虫幼虫挑战的保护性免疫。在这项研究中,Ts87 基因被克隆到表达质粒 pVAX1 中,重组 Ts87 DNA 被转化为减毒鼠伤寒沙门氏菌菌株 SL7207。用减毒鼠伤寒沙门氏菌传递的 Ts87 DNA 对小鼠进行口服免疫,可引起显著的局部黏膜 IgA 反应和全身 Th1/Th2 免疫反应。细胞因子分析还显示,在 Ts87 抗原刺激下,免疫小鼠的脾细胞中 Th1(IFN-γ)和 Th2(IL-5、6、10)反应显著增加。用抗血清进行免疫荧光测定显示,重组 Ts87 蛋白在免疫小鼠的肠系膜淋巴结中表达。与用空鼠伤寒沙门氏菌或 PBS 对照免疫的小鼠相比,用减毒活鼠伤寒沙门氏菌传递的 Ts87 DNA 免疫的小鼠在感染旋毛虫幼虫后,成虫负荷减少了 29.8%,肌肉幼虫减少了 34.2%。我们的结果表明,减毒活鼠伤寒沙门氏菌传递的 Ts87 DNA 可引发局部 IgA 反应和平衡的 Th1/Th2 免疫反应,并在小鼠中产生针对旋毛虫感染的部分保护作用。

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