汉滩病毒嵌合疫苗（VLP/DNA）的制备及其免疫学特性的研究

Hantaan virus (HTNV) is the causative agent of hemorrhagic fever with renal syndrome (HFRS) in China. The control and prevention of HTNV infection are relied on vaccination with inactivated vaccine. An effective HTNV vaccine is highly desirable because the immune responses induced by currently applied inactivated vaccine are weak. Previous studies found that virus-like particle (VLP) vaccine could effectively induce strong humoral immune responses, but the ability of which to induce cellular immune responses was weak and could not consistently induce immune responses. DNA vaccine could consistently induce strong cellular immune responses, but the ability of which to induce humoral immune responses was weak and could be easily digested by nucleicacidase. The studies also found that VLP could be used for DNA delivery, which could protect the DNA from digestion by nucleicacidase and transported it into the cells. Based on previous work, our research will use the HTNV VLP package DNA vaccine to generate chimeric HTNV VLP/DNA vaccine and investigate its immunological properties so as to improve the HTNV antigens’ ability to induce specific immune responses in this chimeric vaccine, and lay a foundation for development of HFRS novel vaccines.

汉滩病毒（HTNV）在我国主要引起肾综合征出血热（HFRS），当前主要使用灭活疫苗进行预防。但HTNV灭活疫苗刺激机体产生免疫应答的能力较弱，因此，如何提高疫苗的免疫效果是HTNV疫苗研究中亟需解决的关键问题。既往研究发现，VLP疫苗能够有效地刺激机体产生较强的体液免疫应答，但刺激机体的细胞免疫应答能力较弱且不能持续刺激机体的免疫反应；DNA疫苗能够持续刺激机体产生较强的细胞免疫应答，但刺激机体的体液免疫应答能力较弱且容易被机体的核酸酶降解。研究还发现，VLP可作为DNA的运载工具，能够保护DNA免受机体核酸酶的降解并将其运送至细胞内。本项目拟在前期工作基础上，用HTNV VLP包裹HTNV DNA疫苗，制备嵌合型HTNV疫苗（VLP/ DNA），并研究其免疫学特性，以期提高该嵌合疫苗中HTNV抗原刺激机体特异性免疫应答的能力，从而为研制HTNV新型疫苗奠定基础。

汉滩病毒（HTNV）在我国主要引起肾综合征出血热（HFRS），当前主要使用灭活疫苗进行预防。但HTNV灭活疫苗刺激机体产生免疫应答的能力较弱，因此，如何提高疫苗的免疫效果是HTNV疫苗研究中亟需解决的关键问题。既往研究发现，VLP疫苗能够有效地刺激机体产生较强的体液免疫应答，但刺激机体的细胞免疫应答能力较弱且不能持续刺激机体的免疫反应；DNA疫苗能够持续刺激机体产生较强的细胞免疫应答，但刺激机体的体液免疫应答能力较弱且容易被机体的核酸酶降解。研究还发现，VLP可作为DNA的运载工具，能够保护DNA免受机体核酸酶的降解并将其运送至细胞内。本项目在前期工作基础上，用HTNV VLP包裹HTNV DNA疫苗，制备嵌合型HTNV疫苗（VLP/ DNA），并研究其免疫学特性，结果发现该嵌合疫苗中HTNV抗原刺激机体特异性免疫应答的能力显著提高，并有效保护了实验动物免受HTNV的攻击，为研制HTNV新型疫苗奠定基础。