【摘要】：只有疫苗才能有效的控制艾滋病的流行。同時(shí)誘導(dǎo)有效的細(xì)胞免疫和體液免疫是研制艾滋病疫苗的目標(biāo)。為了產(chǎn)生更好的細(xì)胞免疫應(yīng)答,近期進(jìn)入臨床試驗(yàn)的疫苗多采用DNA疫苗或重組病毒載體疫苗。而重組病毒載體疫苗主要包括修飾型安卡拉株痘病毒Modified VacciniaAnkara(MVA)載體疫苗以及腺病毒載體疫苗。 但是,活病毒載體疫苗的熱穩(wěn)定性問題阻礙了疫苗的推廣和使用。只有徹底解決疫苗的穩(wěn)定性問題才能保證達(dá)到100%預(yù)防人或動(dòng)物疫苗可預(yù)防疾病的目標(biāo)。解決這個(gè)問題的一個(gè)行之有效的手段就是將疫苗凍干。凍干劑型的疫苗可以在常溫下運(yùn)輸、儲(chǔ)存,有較長(zhǎng)的有效期,質(zhì)量穩(wěn)定。 因此,本研究構(gòu)建了表達(dá)HIV-1主要結(jié)構(gòu)基因的重組MVA病毒載體疫苗和重組腺病毒載體疫苗,首次獲得了熱穩(wěn)定性與免疫原性良好的HIV重組MVA病毒載體疫苗和重組腺病毒載體疫苗的凍干制劑及其制備工藝,并首次提出病毒載體疫苗凍干制劑“Prime-Boost”的聯(lián)合免疫策略,得出先以兩針HIV重組腺病毒載體疫苗凍干制劑免疫小鼠,再用一針HIV重組MVA病毒載體疫苗凍干制劑加強(qiáng)免疫能激發(fā)小鼠產(chǎn)生更強(qiáng)大的免疫應(yīng)答,從而獲得更好的免疫效果的結(jié)論。 該研究將為HIV疫苗研究增加新的免疫策略,為今后艾滋病疫苗免疫程序的改進(jìn)提供理論依據(jù),也為將來在非人靈長(zhǎng)類動(dòng)物模型中的實(shí)驗(yàn)奠定了基礎(chǔ)。
[Abstract]:Only vaccines can effectively control the AIDS epidemic. Inducing effective cellular and humoral immunity at the same time is the goal of AIDS vaccine development. In order to produce better cellular immune response, DNA vaccine or recombinant virus vector vaccine are used in clinical trials recently. The recombinant virus vector vaccine mainly includes modified vaccina Ankara (MVA) vector vaccine and adenovirus vector vaccine. However, the thermal stability of live virus vector vaccine hinders the promotion and use of the vaccine. Only by solving the problem of vaccine stability can the goal of 100% prevention of human or animal vaccine be achieved. One effective way to solve this problem is to freeze the vaccine. The lyophilized vaccine can be transported and stored at room temperature, with a long period of validity and stable quality. Therefore, recombinant MVA vector vaccine and recombinant adenovirus vector vaccine expressing HIV-1 major structural genes were constructed in this study. The freeze-dried preparation of recombinant MVA virus vaccine and recombinant adenovirus vector vaccine with good thermal stability and immunogenicity were obtained for the first time, and the combined immunization strategy of "Prime-Boost" was put forward for the first time. The results showed that mice were immunized with two doses of HIV recombinant adenovirus vector vaccine freeze-dried vaccine, and then one injection of HIV recombinant MVA vector vaccine freeze-dried preparation could stimulate a stronger immune response in mice. In order to obtain a better immune effect of the conclusion. This study will provide a new immune strategy for HIV vaccine research, provide a theoretical basis for the improvement of AIDS vaccine immunization procedures in the future, and lay a foundation for future experiments in non-human primate models.
【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
【分類號(hào)】：R392

【引證文獻(xiàn)】

相關(guān)博士學(xué)位論文 前1條

1 賈立軍;牛源犬新孢子蟲NcSRS2-NcGRA7復(fù)合基因核酸疫苗與重組腺病毒疫苗的研究[D];延邊大學(xué);2012年

相關(guān)碩士學(xué)位論文 前2條

1 曹峰;納豆活性成分冷凍干燥工藝條件及儲(chǔ)存穩(wěn)定性的研究[D];山東輕工業(yè)學(xué)院;2008年

2 胡玉玫;特異性抗體定量檢測(cè)葡聚糖方法的研究[D];廣西大學(xué);2012年

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本文編號(hào)：2124450