發(fā)布時間：2018-02-23 19:42

  本文關(guān)鍵詞： 日本腦炎病毒 GM-CSF 佐劑 pCAG-JEGM 共表達(dá)　出處：《第三軍醫(yī)大學(xué)》2006年碩士論文　論文類型：學(xué)位論文

【摘要】： 日本腦炎病毒(Japaneses encephalitis virus, JEV)又稱乙型腦炎病毒,為黃病毒科單股正鏈RNA病毒,基因組約為11 kb,僅有一個開放閱讀框(open reading frame, ORF ),從5’到3’端排列著3個結(jié)構(gòu)基因(C、prM和E)和7個非結(jié)構(gòu)基因(NS1、NS2A、NS2B、NS3、NS4A、NS4B和NS5),分別編碼相應(yīng)的蛋白。JEV是流行性乙型腦炎(簡稱乙腦)的病原體,經(jīng)蚊蟲叮咬傳播。乙腦主要流行于亞洲東南亞各國及遠(yuǎn)東地區(qū)。JEV感染后往往引發(fā)嚴(yán)重的中樞神經(jīng)系統(tǒng)的癥狀,死亡率較高,幸存者亦有半數(shù)以上發(fā)展為永久的神經(jīng)系統(tǒng)后遺癥。 乙腦尚無有效的治療手段,因此免疫接種是控制其流行、保護(hù)易感人群的重要措施,并且預(yù)防接種對于人類對抗JEV感染已發(fā)揮了良好的保護(hù)作用。目前使用的JEV疫苗主要有三種:一種是由日本研發(fā)的滅活疫苗,采用JEV感染的成年鼠腦經(jīng)福爾馬林滅活純化制成;另外兩種由我國開發(fā)研制,分別為原代地鼠腎細(xì)胞滅活疫苗和經(jīng)SA14-14-2減毒株感染地鼠腎細(xì)胞反復(fù)傳代研制而成的減毒活疫苗,由于生產(chǎn)標(biāo)準(zhǔn)的原因,后兩者僅局限在中國境內(nèi)使用。然而三種疫苗均有其局限性:滅活疫苗存在高生產(chǎn)成本、免疫力不持久、需多次注射及存在變態(tài)反應(yīng)等缺陷;而減毒活疫苗則存在毒力回復(fù)的危險。因此亟待發(fā)展一種安全、有效、質(zhì)優(yōu)價廉的新型疫苗用于對抗JEV引發(fā)的世界范圍內(nèi)的感染。 近年來,核酸DNA疫苗的出現(xiàn)的是替代傳統(tǒng)疫苗的新興策略,與傳統(tǒng)疫苗相比,DNA疫苗具有較多的優(yōu)點,主要在于:(1)在機(jī)體內(nèi)以類似病毒感染的方式合成抗原,從而介導(dǎo)持久的細(xì)胞免疫和體液免疫;(2)DNA疫苗安全穩(wěn)定,易于制備,成本低廉。業(yè)已證明JEV的結(jié)構(gòu)蛋白prM-E和非結(jié)構(gòu)蛋白NS1是保護(hù)性抗原位點集中的部位,將表達(dá)JEV的prM、E或是NS1的質(zhì)粒免疫小鼠后,能夠產(chǎn)生特異性的保護(hù)性免疫,因此認(rèn)為prM-E-NS1基因是JEV DNA疫苗首選靶點。但是單純的DNA疫苗尚不足以引發(fā)良好的免疫效果,為此近年來出現(xiàn)一個較新的策略,即在基因水平將細(xì)胞因子與核酸疫苗共同表達(dá),利用細(xì)胞因子上調(diào)機(jī)體免疫水平的作用,進(jìn)而顯著增強(qiáng)核酸疫苗的效果。粒細(xì)胞-巨噬細(xì)胞集落刺激因子(granulocyte-macrophage colony-stimulating
[Abstract]:Japanese encephalitis virus (Japaneses encephalitis, virus, JEV) and Japanese encephalitis virus family, single strand RNA virus genome was about 11 KB, only one open reading frame (open reading frame, ORF), from the 5 'to 3' end is lined with 3 structural genes (C, prM and E) and 7 non structural genes (NS1, NS2A, NS2B, NS3, NS4A, NS4B and NS5), respectively, the corresponding encoding protein.JEV is Japanese encephalitis (JE) pathogens, the spread of mosquito bites. JE is popular mainly in Southeast Asia and the Far East Asian.JEV infection often causes central nervous serious symptoms, high mortality, there are more than half of survivors for permanent neurological sequelae.
There is no effective treatment for JE vaccination, so is the control of the epidemic, the important measures to protect vulnerable populations, and vaccination against JEV infection in humans has played a good protective effect. There are three main types of currently used JEV vaccine: a vaccine by the Japanese research, formalin inactivated live purification made of JEV infected adult rat brain; the other two by China's development, respectively, primary hamster kidney cell inactivated vaccine and virus infection of hamster kidney cell passaged repeatedly to develop into a live attenuated vaccine by SA14-14-2 reduction, due to production standards, which are only used in the territory of China however. Three kinds of vaccine has its limitations: the inactivated vaccine has high production cost, the lack of long-term immunity, multiple injections and the risk of allergic reactions.; and the live attenuated vaccine is dangerous because of virulence reversion. This is an urgent need to develop a safe, effective, quality and inexpensive new vaccine to fight the worldwide infection caused by JEV.
In recent years, there is a new nucleic acid vaccine DNA strategy to replace the traditional vaccine, compared with the traditional vaccines, DNA vaccines have many advantages, mainly lies in: (1) infection in a similar virus in vivo synthesis of antigen, which mediates cellular immunity and humoral immunity lasting stability; (2) DNA vaccine safety, easy preparation and low cost. It has been proved that the structure of JEV prM-E protein and non structural protein NS1 is a protective antigen site concentration sites, JEV expression of prM, E or immunized mice were NS1, can produce specific protective immunity, so that the prM-E-NS1 gene is JEV DNA the preferred vaccine target. But it is not enough to trigger a DNA vaccine immune effect is good, so in recent years the emergence of a new strategy, which is in the level of gene expression of cytokines and the common use of nucleic acid vaccine, cytokine upregulated immune The effect of the nucleic acid vaccine was significantly enhanced by the effect of the level, and the granulocyte macrophage colony stimulating factor (granulocyte-macrophage colony-stimulating)

【學(xué)位授予單位】：第三軍醫(yī)大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2006
【分類號】：Q789;R392

【引證文獻(xiàn)】

相關(guān)碩士學(xué)位論文 前1條

1 戚龍霞;乙型腦炎病毒E蛋白在桿狀病毒表面的展示及其免疫原性研究[D];西北農(nóng)林科技大學(xué);2010年

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本文編號：1527384