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腹泻是全球范围内引起5岁以下幼童死亡的第二大病因,而产肠毒素大肠杆菌(ETEC)是引起腹泻的最常见病原菌,其产生的细菌定植因子(CFs)和肠毒素是关键的毒力因子。CFs介导细菌黏附宿主小肠上皮细胞并完成定植,产生热敏肠毒素(LT)和热稳定肠毒素(ST)破坏宿主上皮细胞内的体液平衡,使体液和电介质过量分泌从而导致腹泻。预防ETEC腹泻的首选方法是使用能激发宿主产生抗黏附素免疫力和抗肠毒素免疫力的疫苗,阻断ETEC黏附和定植并中和肠毒素。目前一种名为Dukoral~的霍乱疫苗因能刺激机体产生抗热敏毒素免疫,已经被一些国家批准用于短期保护和预防旅行者腹泻。新型试验性ETEC候选疫苗正在研发中,旨在提供保护期长、反应谱广的抗ETEC感染免疫保护力。本文针对疫苗研发的关键问题和研究现状作一综述,并对未来的研究作出展望。
Diarrhea is the second leading cause of death among young children under the age of 5 worldwide, and Enterotoxigenic Escherichia coli (ETEC) is the most common cause of diarrhea and produces bacterial colonization factors (CFs) and enterotoxins that are key Virulence factors. CFs mediate bacterial adhesion to host small intestine epithelial cells and colonization, producing heat-sensitive enterotoxins (LTs) and heat-stable enterotoxins (STs) that disrupt the body fluid balance within host epithelial cells, causing excessive secretion of body fluids and electrolytes resulting in diarrhea. The preferred method of preventing ETEC diarrhea is to use a vaccine that stimulates the host to produce both anti-adhesin and anti-toxin immunity, blocking ETEC adhesion and colonization and neutralizing enterotoxins. Currently a cholera vaccine called Dukoral ~ can stimulate the body to produce heat-sensitive toxin immunity, has been approved by some countries for short-term protection and prevention of traveler’s diarrhea. A new pilot ETEC candidate vaccine is being developed to provide long-term protection and broad-spectrum immunoprotective against ETEC infection. This article reviews the key issues and research status of vaccine development, and looks forward to the future research.