2017年，全球范围内再次暴发汉坦病毒引起的肾综合征出血热（HFRS），使人们对这一再发传染病的防治引起重视。目前，我国上市的疫苗仅针对汉坦病毒的I型（汉滩病毒，HTNV）和II型（汉城病毒，SEOV），为全病毒灭活疫苗，其引起机体的免疫应答偏弱、保护效价偏低，并存在一定副作用及生物安全隐患。本课题拟根据HTNV和SEOV的M基因的高度同源性等优势，运用生物信息学方法，选择每种病毒共同保守区域为基础设计亚单位蛋白疫苗，通过去除基因滞留信号，使用S2果蝇表达系统，达到增加蛋白表达量、可溶性和免疫原性的作用；随后开展小鼠水平的疫苗免疫原性检测、抗病毒保护实验及免疫学机制研究；并最终在非人灵长类动物进行疫苗初步评价。本研究不仅可以验证一种新型HFRS通用疫苗研发策略，而且有可能获得一种保护性和安全性更高的HFRS预防疫苗，在探索关键科学问题和解决传染病防控重大需求两方面都具有十分重要的意义。

In 2017, the recurrence of global outbreak of hemorrhagic fever with renal syndrome has drawn renewed attention to this old disease which seriously threaten human health. At present, only the whole virus inactivated vaccine against type I Hantan virus or type II Seoul virus popular are available in China. The vaccines elicit suboptimal immune responses, confer inadequate protection, and cause safety concerns. To resolve the above problems, we propose to construct a universal genetic engineering novel subunit protein vaccine against HTNV and SEOV by combining bioinformatics methods, viral surface protein structure biology knowledge, and molecular biology tools. Specific aims are: 1) to design the vaccine based on consensus sequences between the two viruses, with a removal to retention signals to increase the solubility of expressed protein; 2) to examine the immunogenicity, antiviral protective efficacy, and epitope recognition in vaccinated mice; and 3) if Aims 1 & 2 were successful, the vaccine will be further evaluated in non-human primates for immunogenicity and protection. This project explores a novel scientific strategy for developing a universal HFRS vaccine; and it evaluates a vaccine prototype which has potential to be developed into an innovative, high-efficiency, broad-spectrum universal HFRS vaccine.