大容量天然人源Fab抗體庫的構(gòu)建及日本血吸蟲抗獨特型抗體的篩
發(fā)布時間:2018-09-19 07:30
【摘要】:血吸蟲病是一種嚴(yán)重危害人民身體健康的人畜共患寄生蟲病。以往的研究證明,以化療為主的血吸蟲病防治策略難以達到阻斷傳播的目的。因此,疫苗成為血吸蟲病防治一項優(yōu)先發(fā)展的策略。血吸蟲本身有多個發(fā)育期,抗原成分復(fù)雜多樣,且日本血吸蟲80%的保護性抗原為多糖或糖蛋白性質(zhì),這些糖類抗原表位在血吸蟲保護性免疫及其調(diào)節(jié)方面起著重要作用,但難以用基因工程方法制備。根據(jù)Jerne的免疫網(wǎng)絡(luò)學(xué)說,抗獨特型抗體(anti-id)可通過其可變區(qū)中的獨特型表位模擬抗原,誘導(dǎo)出與抗原相似的免疫應(yīng)答。管曉虹等根據(jù)此學(xué)說制備了一株日本血吸蟲單克隆抗獨特型抗體NP30,主動免疫小鼠、山羊,具有較好的抗感染免疫和抗病免疫功效。但由于NP30為鼠源性抗體,作為異種蛋白用于人體可產(chǎn)生人抗小鼠抗體(human anti-mouse antibody,HAMA),,從而限制了它在人體的應(yīng)用。本文應(yīng)用噬菌體抗體庫技術(shù),構(gòu)建大容量天然人源Fab抗體庫,從中富集、篩選全人源日本血吸蟲抗獨特型抗體并進行初步鑒定,為研制可用于人體血吸蟲病免疫預(yù)防的抗獨特型抗體疫苗奠定基礎(chǔ)。 材料與方法
[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
【學(xué)位授予單位】:南京醫(yī)科大學(xué)
【學(xué)位級別】:碩士
【學(xué)位授予年份】:2006
【分類號】:R392
本文編號: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
【學(xué)位授予單位】:南京醫(yī)科大學(xué)
【學(xué)位級別】:碩士
【學(xué)位授予年份】:2006
【分類號】:R392
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相關(guān)期刊論文 前4條
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本文編號:2249449
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