2015年寨卡疫情爆发，蔓延至全球80多个国家和地区，我国既有输入病例也在本土蚊虫中分离到寨卡病毒。寨卡病毒可导致成人格林-巴利综合征和新生儿小头症，严重威胁全球公共卫生安全。尽管寨卡疫苗研发已取得一定进展，但寨卡对登革的抗体依赖感染增强效应（ADE）是大家普遍担忧的疫苗安全性问题，特别是考虑到这两种病毒流行地域高度重叠的现实。有学者通过将寨卡病毒疏水融合环（FL）表位进行突变消除了ADE效应，但疫苗免疫原性也显著降低。基于结构生物学分析，本项目拟选用利于寨卡囊膜蛋白结构稳定的FL突变并引入二硫键进一步稳固抗原天然构象的方法，筛选可消除ADE效应兼具良好免疫原性的寨卡疫苗。使用DNA疫苗平台在细胞和动物水平评价疫苗对寨卡病毒的免疫保护效果和对登革病毒感染的ADE效应。该项目将为研制更安全的寨卡疫苗奠定基础并具有较高的应用潜力，也为寨卡和登革病毒之间的免疫互作规律提供新依据。

The 2015 outbreak of Zika epidemic has explosively spilled over 80 countries and regions worldwide. China has imported cases and also has ZIKV isolation in local vector. Zika virus (ZIKV) infection can cause adult Guillain–Barré syndrome and microcephaly in fetuses and newborns. Zika now is the worldwide threat to the public health. Although progresses have been made in vaccine development against ZIKV, the potential antibody-dependent enhancement (ADE) of infection of dengue virus (DENV) caused by ZIKV vaccine has become a widespread safety concern, especially considering the fact of the high degree of overlap between their epidemic areas. Some scholars eliminated ADE effect by mutating fusion loop (FL) of ZIKV, but immunogenicity was also significantly reduced. Based on analysis of structural biology, this project intends to select FL mutation which is beneficial to structural stability of ZIKV capsule protein and introduce disulfide bond to further stabilize the natural conformation of antigen in aim to screen ZIKV vaccine which can eliminate ADE effect and also has good immunogenicity. DNA vaccine platform was used to evaluate vaccine efficacy against ZIKV and ADE potential on DENV by ex vivo and in vivo experiments. This project will lay the foundation for the development of a safer ZIKV vaccine and have promising application potential. Moreover, this project will also provide new evidence for the immunological interplay between ZIKV and DENV.