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重组志贺毒素 B 亚基通过混合 Th 型免疫应答在小鼠中引发针对志贺毒素的保护作用。

Recombinant Shiga toxin B subunit elicits protection against Shiga toxin via mixed Th type immune response in mice.

机构信息

Biotechnology Division, Defence Research and Development Establishment, Gwalior 474002, MP, India.

出版信息

Vaccine. 2011 Oct 19;29(45):8094-100. doi: 10.1016/j.vaccine.2011.08.040. Epub 2011 Aug 19.

Abstract

Shigella dysenteriae is the causative agent of the third commonest bacterial disease for childhood diarrhoea and responsible for millions of deaths per year. It produces potent toxin termed Shiga toxin which is listed in category B biological warfare agent of CDC, USA. Earlier we have reported production of recombinant Shiga toxin B subunit that produced antibodies which neutralized Shiga toxin toxicity in HeLa cells. In the present study, we have evaluated the immunomodulatory potential of rStxB protein in Balb/c mice using Freunds adjuvants. Animal protection with recombinant StxB was conferred through both humoral and cellular immune responses as indicated by an increased antibody titre with predominance of IgG2a and IgG2b isotypes along with elevated levels of IgG1 subtype. Cytokine profile of the mice antiserum and splenocyte also indicates Th2 and Th1 type of immune responses where former dominates in early stage of immunization. Histopathology study of kidneys of vaccinated mice showed remarkable differences when compared to the animals infected with Shigella dysenteriae type1. The present study indicates that recombinant StxB is a promising vaccine candidate and can be used for production of therapeutic antibodies to counter Shiga intoxication.

摘要

志贺氏痢疾杆菌是导致儿童腹泻的第三大常见细菌性疾病的病原体,每年导致数百万人死亡。它产生一种称为志贺毒素的强效毒素,被美国疾病控制与预防中心列为 B 类生物战剂。我们之前曾报道过重组志贺毒素 B 亚基的产生,该亚基产生的抗体可中和 HeLa 细胞中的志贺毒素毒性。在本研究中,我们使用福氏佐剂评估了 rStxB 蛋白在 Balb/c 小鼠中的免疫调节潜力。通过体液和细胞免疫反应赋予重组 StxB 动物保护,如抗体滴度增加,主要是 IgG2a 和 IgG2b 同种型,以及 IgG1 亚型水平升高。小鼠抗血清和脾细胞的细胞因子谱也表明了 Th2 和 Th1 型免疫反应,其中前者在免疫接种的早期阶段占主导地位。与感染志贺氏痢疾杆菌 1 型的动物相比,接种疫苗的小鼠肾脏的组织病理学研究显示出显著差异。本研究表明,重组 StxB 是一种有前途的疫苗候选物,可用于生产治疗性抗体以对抗志贺毒素中毒。

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