HIV多表位重组疫苗的构建及其实验免疫研究

发布时间：2018-11-22 10:09

【摘要】： 本文基于表位识别与递呈的免疫学理论,利用分子生物学、分子病毒学、生物信息学等技术和手段,本着平衡免疫应答、并重点加强CTL诱导的疫苗设计理念,进行了新型HIV重组疫苗抗原基因的分子设计,在HIV非结构蛋白基因与结构蛋白基因中选取了17个优势T细胞表位,插入嵌合抗原基因MEGp24中,获得了新型HIV疫苗多CTL表位嵌合抗原基因MEGNp24。自主构建了基于塞姆利基森林病毒(SFV)RNA复制子的自杀性DNA疫苗载体,并利用安全性真核表达载体质粒pVAX1,将多CTL表位嵌合抗原基因MEGNp24构建了两种DNA候选疫苗;进行了动物实验免疫研究;同时自主构建了新型鸡痘病毒转移载体,进行了候选重组鸡痘病毒疫苗的筛选,为多CTL表位疫苗的联合免疫研究提供了基础。实验免疫研究的特异性CTL检测与Th1/ Th2类细胞因子含量检测分析表明,衍生于SFV的自杀性DNA疫苗具有较强的免疫诱导作用,添加不同佐剂的DNA疫苗的比较结果发现添加佐剂能诱发更强的系统性免疫应答。本研究探讨了新型多表位抗原分子设计的理论和方法,对基于HIV非结构蛋白表位的重组核酸疫苗构建与实验免疫及重组鸡痘病毒疫苗的构建进行了深入研究,为有效HIV重组疫苗的研制与临床前实验研究奠定了基础。
[Abstract]:Based on the immunological theory of epitope recognition and presentation, using molecular biology, molecular virology, bioinformatics and other techniques and means, the immune response was balanced, and the idea of vaccine design induced by CTL was emphasized. The molecular design of novel HIV recombinant vaccine antigen gene was carried out. Seventeen dominant T cell epitopes were selected from HIV non-structural protein gene and inserted into chimeric antigen gene MEGp24. Multiple CTL epitope chimeric antigen gene MEGNp24. of a novel HIV vaccine was obtained. Suicide DNA vaccine vector was constructed based on the (SFV) RNA replicon of Semliki forest virus. Two candidate DNA vaccines were constructed by using the safe eukaryotic expression vector pVAX1, to construct the chimeric antigen gene MEGNp24 of multiple CTL epitopes. At the same time, a novel chicken pox virus transfer vector was constructed, and the candidate recombinant chicken pox virus vaccine was screened, which provided the basis for the combined immunization of multiple CTL epitope vaccines. The detection of specific CTL and Th1/ Th2 cytokines in experimental immunological studies showed that the suicidal DNA vaccine derived from SFV had strong immunogenicity. The comparison of DNA vaccine with different adjuvant showed that the adjuvant could induce a stronger systemic immune response. In this study, the theory and method of novel multiepitope antigen molecular design were discussed. The construction and experimental immunization of recombinant nucleic acid vaccine based on HIV non-structural protein epitope and the construction of recombinant chicken pox virus vaccine were studied. It lays a foundation for the development of effective recombinant HIV vaccine and preclinical experimental research.
【学位授予单位】：吉林大学
【学位级别】：博士
【学位授予年份】：2007
【分类号】：R392

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