Faculty of Life Sciences, University of Manchester, Michael Smith Building, Oxford Road, Manchester M13 9PT, UK.
Int J Parasitol. 2010 May;40(6):683-93. doi: 10.1016/j.ijpara.2009.11.008. Epub 2009 Dec 5.
Trichuris muris is a laboratory model for the human whipworm Trichuris trichiura which infects approximately 1 billion people in tropical and sub-tropical countries. The development of a vaccine would control trichuriasis by promoting the acquisition of immunity during childhood, thereby reducing faecal egg output by the community into their environment. Resistance to T. muris, defined as expulsion of the parasite prior to patency, requires the development of a T helper 2 (Th2) response during a primary infection. To our knowledge this is the first study to describe the protective immune response in the peripheral lymph nodes (PLN), mesenteric lymph nodes (MLN) and colonic mucosa following s.c. vaccination against T. muris. Susceptible AKR mice were either vaccinated with T. muris excretory-secretory product (ES) in incomplete Freund's adjuvant (IFA) (ES/IFA) or injected with PBS in IFA (PBS/IFA) and for protection experiments were infected with embryonated infective T. muris eggs 10 days later. The ES/IFA vaccine induced the proliferation of PLN cells and their production of Th2 cytokines and the Th1-associated cytokine IFN-gamma. Following a challenge infection, the ES/IFA vaccination offered susceptible mice complete protection. While MLN-derived IFN-gamma was produced by infected mice following either ES/IFA vaccination or PBS/IFA, the protection of susceptible mice by ES/IFA was characterised by the production of MLN-derived Th2 cytokines. Goblet cell hyperplasia and the influx and alternative activation of macrophages were observed locally in the gut post-challenge infection. The rate of epithelial turnover did not appear to be increased by vaccination, suggesting that there are differences in the mechanisms of expulsion between 'natural resistance' and 'vaccinated resistance'. High levels of serum IgG1 and cell-bound IgG1 in the colon of mice protected by the ES/IFA vaccine suggest that antibody may be involved in vaccination-induced worm expulsion.
秀丽隐杆线虫是一种实验室模型，用于研究人类鞭虫秀丽隐杆线虫，该寄生虫感染了热带和亚热带国家约 10 亿人。疫苗的开发将通过在儿童时期促进获得免疫力来控制鞭虫病，从而减少社区将粪便虫卵排入环境中的数量。对 T. muris 的抗性，定义为在通畅之前驱除寄生虫，需要在初次感染期间发展 T 辅助 2（Th2）反应。据我们所知，这是第一项描述皮下接种 T. muris 排泄-分泌产物（ES）在不完全弗氏佐剂（IFA）中的保护性免疫应答的研究（ES/IFA）或用 IFA 中的 PBS 注射（PBS/IFA），并在 10 天后用胚胎感染性 T. muris 卵感染以进行保护实验。ES/IFA 疫苗诱导 PLN 细胞增殖及其产生 Th2 细胞因子和 Th1 相关细胞因子 IFN-γ。在挑战感染后，ES/IFA 疫苗为易感小鼠提供了完全保护。虽然 ES/IFA 疫苗接种或 PBS/IFA 后感染小鼠产生 MLN 衍生的 IFN-γ，但 ES/IFA 对易感小鼠的保护作用的特征是 MLN 衍生的 Th2 细胞因子的产生。在挑战感染后，观察到肠道局部杯状细胞增生和巨噬细胞的流入和替代激活。上皮细胞更新率似乎没有因疫苗接种而增加，这表明“天然抗性”和“疫苗抗性”之间的驱出机制存在差异。ES/IFA 疫苗保护的小鼠血清 IgG1 和结肠细胞结合 IgG1 水平高，表明抗体可能参与疫苗诱导的蠕虫驱出。
