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The efficacy of NP11-4-derived immunotoxin scFv-artesunate in reducing hepatic fibrosis inducedby Schistosoma japonicum in mice

查看全文 作  者:Hong [1,2]Li;Chunyan [1,2]Gu;Yongya [1,2]Ren;Yang [3]Dai;Xiaojuan [1,2]Zhu;Jing [1]Xu;Yuhua [2]Li;Zhenning [1]Qiu;Jin [1,4]Zhu;Yinchang [3]Zhu;Xiaohong [1]Guan;Zhenqing [1,2]Feng 高影响力作者 机构地区:[1]Key Labortary of Antibody Technique of Ministry of Health, Nanjing Medical University, Nanjing, Jiangsu 210029, China;[2]Pathology Department, Nanjing Medmal University, Nanjing, Jiangsu 210029, China;[3]Jiangsu Institute of Parasitic Diseases, Wuxi, Jiangsu 214000, China;[4]Huadong Medical Institute of Bioteehniques, Nanjing, Jiangsu 210002, China高影响力机构 出  处:《The Journal of Biomedical Research》索引2011年第25卷第2期,共7页高影响力期刊 基  金:supported by a grant from the National High Technology Research and Development Program of China ('863'ProgramNo.2006AA02Z415) 摘  要:Schistosomiasis is one of the most prevalent parasitic diseases in China,and hepatic fibrosis caused by schistosome infection is the principal cause of death.The aim of this study was to evaluate the efficacy of NP11-4derived immunotoxin scFv-artesunate on Schistosoma japonicum-induced hepatic fibrosis.A single-chain variable fragment (scFv) was generated from the murine anti-Schistosoma japonicum (S.japanicum) monoclonal antibody NP11-4.The scFv was expressed as a soluble protein and purified by Ni-affinity chromatography.After conjugation 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.After 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 animal 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. 关 键 词:肝纤维化 免疫毒素 单链抗体 青蒿琥酯 血吸虫病 疗效 小鼠 酶联免疫吸附试验
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