缺失突变HCV核蛋白DNA免疫效果的初步评价

发布时间：2018-06-19 03:57

本文选题：丙型肝炎病毒 + 核蛋白　；参考：《第四军医大学》2005年博士论文

【摘要】：丙型肝炎病毒(hepatitis C virus,HCV)感染已成为困扰全球人口健康的一大问题,超过1.7亿人有HCV感染。HCV感染后85%将发展为慢性,约20%最终发展为终末期肝病。到目前为止尚无切实有效的预防和治疗方法。因此,迫切需要开发切实有效的疫苗来预防感染和寻求新的治疗途径。长期以来,HCV核蛋白作为抗HCV疫苗的备选抗原一直受到关注。DNA免疫研究揭示编码HCV核蛋白的DNA疫苗能够诱导特异性抗体产生和Th1类细胞免疫反应,然而由于完整的核蛋白基因疫苗免疫原性十分有限,促使研究者寻求多种策略进行优化,但仍然未达到理想的效果。核蛋白DNA疫苗在细胞内表达量不足和核蛋白本身对免疫功能的抑制作用可能是影响提高核蛋白特异性免疫的两个重要因素。本研究着眼于对核蛋白自身结构的改造,试图通过提高核蛋白在真核细胞内的表达水平、去除影响免疫细胞对核蛋白有效识别的肽段,达到增强核蛋白特异性免疫反应的目的。实验方法和结果: 1.通过RT-PCR方法从西安地区慢性丙型肝炎患者血清中扩增了HCV C区及部分E1区cDNA,将其插入pGEM-Teasy载体中,采用酶切
[Abstract]:Hepatitis C virus (HCV) infection has become a major health problem in the world. More than 170 million people have HCV infection. 85% of them will become chronic after infection, and about 20% will eventually develop into end-stage liver disease. So far, there are no effective prevention and treatment methods. Therefore, there is an urgent need to develop effective vaccines to prevent infection and seek new ways of treatment. For a long time, HCV nucleoprotein as an alternative antigen of anti-HCV vaccine has been concerned. DNA immunological studies have revealed that the DNA vaccine encoding HCV nucleoprotein can induce specific antibody production and Th1 cell immune response. However, due to the limited immunogenicity of the complete nucleoprotein gene vaccine, many strategies have been sought for optimization, but the desired results have not been achieved. The insufficient expression of nucleoprotein DNA vaccine in cells and the inhibition of nuclear protein itself on immune function may be two important factors affecting the enhancement of specific immunity of nucleoprotein. The aim of this study is to improve the expression level of nucleoprotein in eukaryotic cells and to remove the peptides that affect the effective recognition of nucleoprotein in order to enhance the specific immune response of nucleoprotein. Experimental methods and results: 1. The HCV C region and some E1 region cDNAs were amplified by RT-PCR from the serum of patients with chronic hepatitis C in Xi'an area. They were inserted into pGEM-T easy vector and digested by enzyme.
【学位授予单位】：第四军医大学
【学位级别】：博士
【学位授予年份】：2005
【分类号】：R392

【引证文献】