大容量天然人源Fab抗体库的构建及日本血吸虫抗独特型抗体的筛
发布时间：2018-09-19 07:30
【摘要】：血吸虫病是一种严重危害人民身体健康的人畜共患寄生虫病。以往的研究证明，以化疗为主的血吸虫病防治策略难以达到阻断传播的目的。因此，疫苗成为血吸虫病防治一项优先发展的策略。血吸虫本身有多个发育期，抗原成分复杂多样，且日本血吸虫80％的保护性抗原为多糖或糖蛋白性质，这些糖类抗原表位在血吸虫保护性免疫及其调节方面起着重要作用，但难以用基因工程方法制备。根据Jerne的免疫网络学说，抗独特型抗体(anti-id)可通过其可变区中的独特型表位模拟抗原，诱导出与抗原相似的免疫应答。管晓虹等根据此学说制备了一株日本血吸虫单克隆抗独特型抗体NP30，主动免疫小鼠、山羊，具有较好的抗感染免疫和抗病免疫功效。但由于NP30为鼠源性抗体，作为异种蛋白用于人体可产生人抗小鼠抗体(human anti-mouse antibody，HAMA)，，从而限制了它在人体的应用。本文应用噬菌体抗体库技术，构建大容量天然人源Fab抗体库，从中富集、筛选全人源日本血吸虫抗独特型抗体并进行初步鉴定，为研制可用于人体血吸虫病免疫预防的抗独特型抗体疫苗奠定基础。 材料与方法
[Abstract]:Schistosomiasis is a zoonotic parasitic disease that seriously endangers people's health. Previous studies have proved that chemotherapy-based schistosomiasis control strategies are difficult to block transmission. Therefore, vaccine has become a priority development strategy for schistosomiasis control. Schistosoma japonicum has many developmental stages, complex and diverse antigenic components, and 80% of the protective antigens of Schistosoma japonicum are polysaccharides or glycoproteins. These carbohydrate epitopes play an important role in the protective immunity and regulation of Schistosoma japonicum. But it is difficult to prepare by genetic engineering. According to Jerne's immune network theory, anti-idiotypic antibodies (anti-id) can induce antigen-like immune responses by mimicking the idiotypic epitopes in their variable regions. According to this theory, Guan Xiaohong prepared a monoclonal anti-idiotypic antibody (NP30,) from Schistosoma japonicum to immunize mice and goats. However, the application of NP30 in human body is limited because it is a mouse antibody and is used as a xenogeneic protein to produce human anti-mouse antibody (human anti-mouse antibody,HAMA). In this paper, a large capacity natural human Fab antibody library was constructed by using phage antibody library technology, from which human Schistosoma japonicum anti-idiotypic antibody was screened and preliminarily identified. It lays a foundation for the development of anti-idiotypic antibody vaccine which can be used to prevent human schistosomiasis. Materials and methods
【学位授予单位】：南京医科大学
【学位级别】：硕士
【学位授予年份】：2006
【分类号】：R392
本文编号：2249449
[Abstract]:Schistosomiasis is a zoonotic parasitic disease that seriously endangers people's health. Previous studies have proved that chemotherapy-based schistosomiasis control strategies are difficult to block transmission. Therefore, vaccine has become a priority development strategy for schistosomiasis control. Schistosoma japonicum has many developmental stages, complex and diverse antigenic components, and 80% of the protective antigens of Schistosoma japonicum are polysaccharides or glycoproteins. These carbohydrate epitopes play an important role in the protective immunity and regulation of Schistosoma japonicum. But it is difficult to prepare by genetic engineering. According to Jerne's immune network theory, anti-idiotypic antibodies (anti-id) can induce antigen-like immune responses by mimicking the idiotypic epitopes in their variable regions. According to this theory, Guan Xiaohong prepared a monoclonal anti-idiotypic antibody (NP30,) from Schistosoma japonicum to immunize mice and goats. However, the application of NP30 in human body is limited because it is a mouse antibody and is used as a xenogeneic protein to produce human anti-mouse antibody (human anti-mouse antibody,HAMA). In this paper, a large capacity natural human Fab antibody library was constructed by using phage antibody library technology, from which human Schistosoma japonicum anti-idiotypic antibody was screened and preliminarily identified. It lays a foundation for the development of anti-idiotypic antibody vaccine which can be used to prevent human schistosomiasis. Materials and methods
【学位授予单位】：南京医科大学
【学位级别】：硕士
【学位授予年份】：2006
【分类号】：R392
【参考文献】
相关期刊论文 前4条
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本文编号：2249449
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