日本血吸虫RNA疫苗探索及Sj23抗原对宿主免疫调节机制的研究

发布时间：2018-04-05 08:40

本文选题：日本血吸虫　切入点：RNA疫苗　出处：《吉林大学》2009年博士论文

【摘要】： 血吸虫病是世界上严重危害人类和动物健康的人兽共患寄生虫病之一,流行于我国的日本血吸虫病是所有血吸虫病中防治难度最大的一种。近百年来人们在日本血吸虫弱毒苗、亚单位苗、DNA疫苗研究方向上进行了大量尝试,但进展不明显,效果均不理想。为了进一步探索新的疫苗途径和日本血吸虫对宿主的免疫调节机制,本研究从虫体的主要疫苗候选分子中选取了编码日本血吸虫主要抗原:谷胱甘肽-S-转移酶(GST)和日本血吸虫23kD膜蛋白(Sj23)的基因,制备了含有日本血吸虫GST抗原、Sj23抗原及GST-Sj23嵌合体抗原mRNA的假病毒颗粒,并对其免疫原性和保护作用进行了试验研究。研究发现经上述抗原免疫小鼠后所获得的保护作用与抗体应答无正相关。进一步研究发现Sj23抗原是虫体早期反应抗原,具有很高的抗原性,但机体产生的抗Sj23抗体无保护作用。其主要原因是Sj23本身是一种免疫调节抗原。Sj23是日本血虫四次跨膜蛋白质家族成员之一,具有独特分子结构特征,对人体IgG分子具有亲合力,激发宿主产生以IgG2为主的非细胞嗜性抗体,同时抑制机体对其他抗原的应答反应,进而逃避机体的免疫清除。本研究认为Sj23很可能是日本血吸虫的一种免疫调节抗原,其作为疫苗候选抗原的可行性有待于深入研究。研究结果对揭示日本血吸虫的致病及免疫逃避机理具有重要的意义。
[Abstract]:Schistosomiasis japonicum is one of the most serious human and animal parasitic diseases in the world. Schistosomiasis japonicum which is prevalent in China is one of the most difficult to control schistosomiasis.A lot of attempts have been made in the research direction of Schistosoma japonicum attenuated vaccine and subunit vaccine in the past century, but the progress is not obvious and the effect is not satisfactory.In order to further explore the new vaccine pathway and the immune regulatory mechanism of Schistosoma japonicum to the host,In this study, the genes encoding the main antigens of Schistosoma japonicum, glutathione--Stransferase (GST) and Schistosoma japonicum 23kD membrane protein (Sj23), were selected from the main vaccine candidate molecules of Schistosoma japonicum.Pseudoviral particles containing Schistosoma japonicum GST antigen Sj23 and GST-Sj23 chimeric antigen mRNA were prepared and their immunogenicity and protective effect were studied.It was found that the protective effects of the above-mentioned antigens were not positively correlated with the antibody response.It was further found that Sj23 antigen is the early reaction antigen of parasite and has high antigenicity, but the anti Sj23 antibody produced by the body has no protective effect.The main reason is that Sj23 itself is a kind of immunomodulatory antigen. Sj23 is a member of the four-time transmembrane protein family of Haemonema japonicus, which has unique molecular structure and affinity to human IgG molecule.The host was stimulated to produce non-cellular antibodies, which were mainly IgG2, and the response to other antigens was inhibited, and then immune clearance was avoided.This study suggests that Sj23 is probably an immunomodulatory antigen of Schistosoma japonicum, and its feasibility as a vaccine candidate antigen needs further study.The results are of great significance to reveal the pathogenesis and immune escape mechanism of Schistosoma japonicum.
【学位授予单位】：吉林大学
【学位级别】：博士
【学位授予年份】：2009
【分类号】：R392

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