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日本血吸蟲RNA疫苗探索及Sj23抗原對宿主免疫調(diào)節(jié)機(jī)制的研究

發(fā)布時間:2018-04-05 08:40

  本文選題:日本血吸蟲 切入點(diǎn):RNA疫苗 出處:《吉林大學(xué)》2009年博士論文


【摘要】: 血吸蟲病是世界上嚴(yán)重危害人類和動物健康的人獸共患寄生蟲病之一,流行于我國的日本血吸蟲病是所有血吸蟲病中防治難度最大的一種。近百年來人們在日本血吸蟲弱毒苗、亞單位苗、DNA疫苗研究方向上進(jìn)行了大量嘗試,但進(jìn)展不明顯,效果均不理想。 為了進(jìn)一步探索新的疫苗途徑和日本血吸蟲對宿主的免疫調(diào)節(jié)機(jī)制,本研究從蟲體的主要疫苗候選分子中選取了編碼日本血吸蟲主要抗原:谷胱甘肽-S-轉(zhuǎn)移酶(GST)和日本血吸蟲23kD膜蛋白(Sj23)的基因,制備了含有日本血吸蟲GST抗原、Sj23抗原及GST-Sj23嵌合體抗原mRNA的假病毒顆粒,并對其免疫原性和保護(hù)作用進(jìn)行了試驗研究。 研究發(fā)現(xiàn)經(jīng)上述抗原免疫小鼠后所獲得的保護(hù)作用與抗體應(yīng)答無正相關(guān)。進(jìn)一步研究發(fā)現(xiàn)Sj23抗原是蟲體早期反應(yīng)抗原,具有很高的抗原性,但機(jī)體產(chǎn)生的抗Sj23抗體無保護(hù)作用。其主要原因是Sj23本身是一種免疫調(diào)節(jié)抗原。Sj23是日本血蟲四次跨膜蛋白質(zhì)家族成員之一,具有獨(dú)特分子結(jié)構(gòu)特征,對人體IgG分子具有親合力,激發(fā)宿主產(chǎn)生以IgG2為主的非細(xì)胞嗜性抗體,同時抑制機(jī)體對其他抗原的應(yīng)答反應(yīng),進(jìn)而逃避機(jī)體的免疫清除。本研究認(rèn)為Sj23很可能是日本血吸蟲的一種免疫調(diào)節(jié)抗原,其作為疫苗候選抗原的可行性有待于深入研究。研究結(jié)果對揭示日本血吸蟲的致病及免疫逃避機(jī)理具有重要的意義。
[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.
【學(xué)位授予單位】:吉林大學(xué)
【學(xué)位級別】:博士
【學(xué)位授予年份】:2009
【分類號】:R392

【引證文獻(xiàn)】

相關(guān)博士學(xué)位論文 前2條

1 洪煬;日本血吸蟲童蟲在不同敏感性宿主體內(nèi)差異表達(dá)蛋白的研究[D];南京農(nóng)業(yè)大學(xué);2011年

2 韓凱凱;捻轉(zhuǎn)血矛線蟲甘油醛-3-磷酸脫氫酶DNA疫苗的免疫保護(hù)作用與烯醇化酶特性的研究[D];南京農(nóng)業(yè)大學(xué);2011年

相關(guān)碩士學(xué)位論文 前1條

1 曹仁祺;日本血吸蟲病環(huán)介導(dǎo)等溫擴(kuò)增診斷方法的建立和初步應(yīng)用[D];華中農(nóng)業(yè)大學(xué);2010年



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