The efficacy of NP11-4-derived immunotoxin scFv-artesunate in reducing hepatic fibrosis induced by Schistosoma japonicum in mice
Hong Li
Chunyan Gu
Yongya Ren
Yang Dai
Xiaojuan Zhu
Jing Xu
Yuhua Li
Zhenning Qiu
Jin Zhu
Yinchang Zhu
Xiaohong Guan
Zhenqing Feng
摘要：Schistosomiasis is one of the most prevalent parasitic diseases in China, and hepatic fibrosis caused by schis- tosome infection is the principal cause of death. The aim of this study was to evaluate the efficacy of NP11-4- derived immunotoxin scFv-artesunate on Schistosoma japonicum-induced hepatic fibrosis. A single-chain variable fragment (scFv) was generated from the routine anti-Schistosoma japonicum (S.japanicum) monoclonal antibody NP11-4. The scFv was expressed as a soluble protein and purified by Ni-affinity chromatography. After conjuga- tion with artesunate, the binding ability with soluble egg antigens (SEA) was determined by an enzyme-linked immunosorbent assay (ELISA). The biological activity of purified scFv, scFv-artesunate (immunotoxin), and artesunate was detected in vivo. Image-Pro Plus software was used to analyze the size of egg granuloma and the extent of liver fibrosis. The recombinant scFv expession vector was constructed and expressed successfully. Af-ter purification by a His-trap Ni-affinity column, the scFv yield was approximately 0.8 mg/L of culture medium. ELISA results showed that chemical conjugation did not affect the binding activity of the immunotoxin. Our ani- mal experiments indicated that the immunotoxin could significantly reduce the size of egg granuloma in the liver and inhibit hepatic fibrosis. The immunotoxin could be used as a promising candidate in the targeted therapy of S. japonicum-induced hepatic fibrosis.
机标关键词：miceSchistosoma japonicumhepatic fibrosisscFvbiological activitytargeted therapysoluble proteinSchistosomiasis
分类号：R575.2(消化系及腹部疾病)
资助基金：This work was supported by a grant from the National High Technology Research and Development Program of China(2006AA02ZA415)
论文发表日期：2011-01-01
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
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