抗日本血吸虫未成熟卵单链抗体与IL-18融合基因对虫卵肉芽肿形成的影响

Schistosome eggs is the main cause of schistosomiasis and also is the only factor as the transmission of schistosomiasis. Studies have shown that praziquantel therapy has little effect on either the immature eggs or the formed egg granulomas, while it aims at schistosoma adults. As a result, these immature eggs can continue developing to mature in the liver and intestine tissue and induce the egg granuloma response. The pathological changes causing mature egg couldn’t terminate after treatment by praziquantel. As we known, the formation of egg granulomas plays a pivotal role in the process of schistosomiasis. Therefore, if the intervention against the immature eggs could be performed at the earliest stage, and the formation of egg granuloma could be directly inhibited or blocked. Then, praziquantel therapy can be compensated at the same time, the effects of irradiation and transmission from mature eggs maybe also blocked. Based on the constructing and screening of immature eggs single-chain Fv antibody (scFv) library of Schistosoma japonicum, we confirmed that the immature egg scFv can specifically recognize the female adults and immature eggs as well as inhibit the development of embryonation and female fecundity. This study is based on the high specificity of immature egg scFv for targeting immune recognition to female and immature eggs, therefore the scFv-IL-18 fusion gene could be targeting carried by scFv into the local area around the immature egg and egg granuloma. We shall observe its effect on formation of granuloma and reveal the immunomodulatory molecular mechanisms of scFv-IL18 fusion gene against Schistosoma japonicum egg granuloma formation in vivo and in vitro.

血吸虫卵既是血吸虫病致病的主要因素，又是造成血吸虫病传播的惟一因子。研究证明，吡喹酮杀虫治疗主要针对成虫，而对未成熟阶段及已经形成的虫卵肉芽肿效果不理想，治后病人肝肠组织内的未成熟卵仍可继续发育成熟，虫卵肉芽肿形成与发展所致的免疫病理变化并不因杀虫治疗而终止。虫卵肉芽肿的形成是血吸虫病发生发展的关键。因此，如能针对未成熟卵进行早期干预，直接抑制或阻断虫卵肉芽肿的形成，既可弥补吡喹酮杀虫治疗的不足，又可阻断虫卵传染源的扩散与传播。基于成功构建日本血吸虫未成熟卵单链抗体库、筛选获得抗日本血吸虫未成熟卵单链抗体的研究基础，我们发现未成熟卵单链抗体不但具有对血吸虫雌虫和未成熟虫卵特异的免疫识别能力，并能抑制雌虫生殖产卵和虫卵胚胎发育与成熟。本研究拟进一步通过体内外实验，观察未成熟卵单链抗体与IL-18融合基因靶向免疫识别、早期干预虫卵肉芽肿形成的效果，并揭示其抗虫卵肉芽肿形成的免疫调节的分子机制。