汉滩病毒新型疫苗--免疫增强型VLPs疫苗的构建、免疫学特性和免疫保护作用的研究

项目名称： 汉滩病毒新型疫苗--免疫增强型VLPs疫苗的构建、免疫学特性和免疫保护作用的研究

项目编号： No.31470890

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 生物科学

项目作者： 吴兴安

作者单位： 中国人民解放军第四军医大学

项目金额： 85万元

中文摘要： 汉滩病毒（HTNV）在我国主要引起肾综合征出血热（HFRS），该病危害极为严重，且缺乏特效的治疗药物，目前主要使用疫苗进行预防。使用最多的是灭活疫苗，虽有一定的免疫保护作用，但尚存在刺激机体产生免疫应答能力弱等不足。因此，急需研制免疫效果好、安全有效的HTNV新型疫苗。病毒样颗粒（VLPs）疫苗是一种新的候选疫苗，已被广泛用于新型疫苗的研制，但其免疫原性尚待进一步提高。本课题组前期已在哺乳动物细胞中成功包装出HTNV VLPs，在此基础上本项目拟将免疫刺激分子GM-CSF和CD40L与HTNV 结构蛋白融合，包装出HTNV嵌合VLPs，以期提高其免疫原性。将构建的嵌合VLPs疫苗免疫小鼠，通过系列体、内外实验对其免疫学特性和动物保护作用进行系统研究，评价其免疫应答能力和免疫保护效果；同时对HTNV嵌合VLPs的免疫机制和安全性进行初步探讨，从而为HTNV新型疫苗的研制奠定基础。

中文关键词： 汉滩病毒；疫苗；嵌合病毒样颗粒；粒细胞巨噬细胞集落刺激因子；CD40配体

英文摘要： Hantaan virus is the causative agent of hemorrhagic fever with renal syndrome with high mortality in China, but with no specific antiviral therapeutics. The control and prevention of HTNV infection is relied on vaccination. However, the effect of immune response induced by the currently applied vaccines is not good enough. Thus, there is an urgent need for developing an effective and safe vaccine. As a new form of vaccine candidate, virus-like particles (VLPs) has been reported to be potent vaccines for a variety of pathogenic viruses. Although VLPs are a promising candidate vaccines, it is highly desirable to develop approaches to enhance the immunogenicity of VLPs such that both efficacious humoral and cellular immune responses can be in induced. To develop a more effective hantaan virus vaccine, we design a chimeric HTNV VLP vaccine by incorporating GM-CSF or CD40L, which have been extensively used as effective genetic and protein adjuvants to enhance immunogenicity of antigens, into VLP as a molecular adjuvant. In this project, we express a glycosylphosphatidylinositol (GPI)-anchored form GM-CSF and CD40L for production of chimeric HTNV VLPs.We then investigate their immunological characteristics, their ability of protection against hantaan virus in mouse model, the mechanism of immune response and their safety, laying the groundwork for the development of HTNV vaccine.

英文关键词： Hantaan virus;vaccine;chimeric VLPs;GM-CSF;CD40L