本文選題：HBV + HBcAg��； 參考：《吉林大學(xué)》2006年博士論文

【摘要】：乙肝是一種嚴(yán)重威脅人類(lèi)健康的傳染病,目前臨床治療仍沒(méi)有特效藥物。許多研究證實(shí),細(xì)胞免疫和體液免疫在阻止HBV感染和病毒清除方面起到了關(guān)鍵的作用。因此,開(kāi)發(fā)能特異增強(qiáng)機(jī)體細(xì)胞免疫和/或體液免疫的乙肝治療性藥物是該領(lǐng)域研究的熱點(diǎn)。 乙肝核心抗原(HBcAg)由于其獨(dú)特的物理結(jié)構(gòu)和免疫學(xué)性質(zhì)而被人們認(rèn)為是一種良好的分子載體。本研究利用基因工程技術(shù)對(duì)HBcAg基因e1區(qū)進(jìn)行了修飾,使其變?yōu)槟軌蛄己眠f呈外源基因的分子載體。將前S1表位基因插入該區(qū),構(gòu)建了含有HBcAg和前S1表位融合基因的原核表達(dá)載體pBTcs1。在大腸桿菌中表達(dá)后,融合蛋白BTcs1經(jīng)蔗糖密度梯度超速離心純化。蛋白鑒定結(jié)果顯示,融合蛋白BTcs1分子量約為28 kDa,能夠與抗-preS1抗體和抗-HBc抗體特異雜交,且能夠自主組裝成病毒樣顆粒(VLPs)結(jié)構(gòu),顆粒直徑約為30-34 nm。融合蛋白BTcs1免疫Balb/c小鼠后,能夠誘導(dǎo)出高滴度的保護(hù)抗體和Th1型免疫反應(yīng),表明BTcs1可能發(fā)展成為一種兼有預(yù)防和治療作用的新型HBV疫苗。
[Abstract]:Hepatitis B is a serious threat to human health infectious disease, the current clinical treatment is still no special drugs. Many studies have confirmed that cellular and humoral immunity play a key role in preventing HBV infection and virus clearance. Therefore, the development of hepatitis B therapeutic drugs that can specifically enhance cellular and / or humoral immunity is a hot topic in this field. Hepatitis B core antigen (HBcAg) is considered to be a good molecular carrier because of its unique physical structure and immunological properties. In this study, the gene engineering technique was used to modify the e1 region of HBcAg gene so that it could be transformed into a molecular vector capable of presenting foreign genes well. The prokaryotic expression vector pBTcs1 containing HBcAg and preS1 epitope fusion gene was constructed by inserting preS1 epitope gene into the region. After expression in E. coli, the fusion protein BTcs1 was purified by sucrose density gradient ultracentrifugation. The results of protein identification showed that the molecular weight of the fusion protein BTcs1 was about 28kDa. the fusion protein could be hybridized with anti-preS1 antibody and anti-HBc antibody. The fusion protein could be assembled into virus-like particles with a diameter of about 30-34 nm. The fusion protein BTcs1 immunized Balb/c mice could induce high titers of protective antibody and Th1 type immune response, indicating that BTcs1 might develop into a novel HBV vaccine with both preventive and therapeutic effects.
【學(xué)位授予單位】：吉林大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2006
【分類(lèi)號(hào)】：R392

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相關(guān)期刊論文 前3條

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本文編號(hào)：1917253