寨卡病毒（ZIKV）可经垂直传播导致不良妊娠结局，母体预存的异种黄病毒交叉免疫力在该途径中具重要作用。我国健康人群大多具有乙脑病毒（JEV）免疫力，而母体JEV免疫力在ZIKV垂直传播中扮演的角色尚未明确。我们和同行均发现，小鼠接种JEV减毒活疫苗后，尽管免疫血清对ZIKV存在抗体依赖感染增强（ADE）作用，但交叉T细胞反应仍可保护小鼠以抵抗ZIKV感染。故我们推测母体预存的交叉T细胞可阻断ZIKV垂直传播，但当其功能衰减甚至耗竭时，交叉IgG抗体可增强胎盘感染使胚胎异常。本项目拟利用小鼠模型首先从母婴双方综合评价母体因接种JEV疫苗而预存的免疫力在孕早期ZIKV感染中发挥的交叉保护作用；再通过疫苗接种小鼠的T细胞或IgG抗体过继转移、T细胞耗竭或ADE关键受体FcRn封闭，明确二者在ZIKV垂直传播中的作用及其机制。结果将对相关孕妇感染ZIKV后的妊娠风险评估和转归预测具有重要参考价值。

Zika virus (ZIKV) can cause various adverse pregnancy outcomes through vertical transmission. Pre-existing, cross-reactive, heterologous immunity to flaviviruses in pregnant women plays a key role in modulating ZIKV vertical transmission. Most healthy people in China have immunity to Japanese encephalitis (JE) due to vaccination or natural exposure, but it is currently unclear what role pre-existing JE virus (JEV) immunity in pregnant women will play in the vertical transmission of ZIKV. Our research and that of some of our peers have revealed that mice vaccinated with the live attenuated JE vaccine can protect against ZIKV infection, with cross-reactive T cell responses playing an essential role. Conversely, sera from the JE-immunized mice mediate antibody-dependent enhancement (ADE) of ZIKV infection. Therefore, we hypothesize that the cross-reactive T cell response conferred by maternal JE vaccination can block the vertical transmission of ZIKV and protect both the mother and the baby, whereas the cross-reactive IgG antibody response can enhance placental infection with ZIKV, leading to embryo abnormalities or fetal developmental disorders. The final clinical outcome will depend on the balance between these two factors. In this study, we will inoculate female mice with the JE vaccine, mate them, and subsequently challenge them with ZIKV to evaluate the protective effect of JE vaccine-induced cross-immunity against ZIKV infection during early pregnancy. Next, T cells or IgG antibodies from the immunized mice will be adoptively transferred to naïve mice, T cells of the vaccinated mice will be depleted, or FcRn, a key ADE receptor, will be blocked to conclusively show the protective effects of the JE vaccine mediated by cross-reactive T cells, not IgG antibodies, which are harmful in ZIKV vertical transmission through ADE. The results of this study will be important for public health, as they will suggest that the JE vaccine is a tool that can rapidly be deployed to mitigate ZIKV infection during pregnancy to prevent adverse outcomes.