Flt3配体胞外段及HBcAg真核双表达载体的构建与体外表达研究

发布时间：2019-06-15 02:10

【摘要】：全球有超过3.5亿的乙型肝炎病毒(hepatitis B virus,HBV)感染患者,使得HBV感染成为对人类健康造成危害的最严重疾病之一,其中有15-25%的HBV感染患者最终会死于HBV相关性疾病,如:终末期肝硬化、肝癌等,每年死亡人数就达100万以上。因此,治疗HBV持续性感染对人类健康有着重大的意义。HBV感染慢性化的发病机制中,特异性细胞免疫力低下或不足起着至关重要的作用。小鼠和灵长类动物的研究均证实HBV的核酸疫苗有着较好的免疫原性,能有效激发机体产生了细胞免疫应答,但在作为治疗性疫苗时其免疫原性和免疫效果却仍需进一步提高。 Flt3配体(Flt3 ligand,FL)是1993年首先发现并被成功克隆的一种早期造血细胞生长因子,能刺激树突状细胞(dendritic cell,DC)及其祖细胞的增殖与分化。由于DC在免疫应答中摄取加工及递呈抗原起着关键性作用,因此,FL自发现以来就受到了广泛的关注。近来的研究表明,细胞因子作为免疫活性分子能明显提高疫苗的免疫原性和免疫应答效果,在HIV、HCV和肿瘤疫苗的研究中证实FL明显提高了其的免疫应答水平,有效产生了细胞免疫应答。基于以上的最新研究成果,我们拟通过构建HBcAg和FL的双表达型核酸疫苗,以期有效提高HBV核酸疫苗的免疫原性,更好地刺激机体产生细胞免疫应答,为研究治疗型乙肝疫苗进一步打下基础。
[Abstract]:There are more than 350 million patients with hepatitis B virus (hepatitis B virus,HBV) infection in the world, which makes HBV infection one of the most serious diseases harmful to human health. 15% of the patients with HBV infection will eventually die from HBV-related diseases, such as end-stage liver cirrhosis, liver cancer and so on, and the annual death toll is more than 1 million. Therefore, the treatment of persistent HBV infection is of great significance to human health. The low or insufficient immunity of specific cells plays an important role in the pathogenesis of chronic HBV infection. The studies of mice and primates have confirmed that the nucleic acid vaccine of HBV has good immunogenicity and can effectively stimulate the cellular immune response, but its immunogenicity and immune effect still need to be further improved as a therapeutic vaccine. Flt3 ligand (Flt3 ligand,FL) is an early hematopoietic growth factor first discovered and successfully cloned in 1993, which can stimulate the proliferation and differentiation of dendritic cells (dendritic cell,DC) and their progenitor cells. Because DC plays a key role in the uptake, processing and presentation of antigens in immune response, FL has received extensive attention since its discovery. Recent studies have shown that cytokines as immunoactive molecules can significantly improve the immunogenicity and immune response of the vaccine. In the study of HIV,HCV and tumor vaccine, it has been confirmed that FL significantly improves the level of immune response and effectively produces cellular immune response. Based on the above latest research results, we intend to construct the double expression nucleic acid vaccine of HBcAg and FL in order to effectively improve the immunogenicity of HBV nucleic acid vaccine and better stimulate the cellular immune response, so as to lay a further foundation for the study of therapeutic hepatitis B vaccine.
【学位授予单位】：南京医科大学
【学位级别】：硕士
【学位授予年份】：2005
【分类号】：R392

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