Zika virus (ZIKV) and Japanese encephalitis virus (JEV) are closely related flaviviruses, ZIKV circulates in the population that has been JEV vaccinated in Southeast Asian countries. This alerts that a pre-existing immunity to JEV would impact ZIKV infection and/or pathogenesis. Herein we showed that the pre-existing immunity to JEV SA14-14-2 vaccination provided an ample protection against non-lethal or lethal dose of ZIKV infection in mice. This was in sharp contrast to the passive immunization of JEV antibodies, which failed to affect ZIKV infection or pathogenesis in mice, albeit these antibodies exhibited cross-reactivity and antibody dependent enhancement (ADE) of ZIKV infection in vitro. Furthermore, we determined that JEV vaccine-elicited CD8⁺ T cells were required to mediate the heterotypic protection of ZIKV infection, which cross-reacted to ZIKV E and NS5 antigens (E_294-302 and NS5_2839-2848). Adoptive transfer of these CD8⁺T cells could partially protected the mice from ZIKV challenge. Therefore, although short of epidemiological evidence, these results suggested that cross-reactive CD8⁺ T cells activated by JEV vaccination could protect potential ZIKV infection in human populations.

寨卡病毒（ZIKV）和日本脑炎病毒（JEV）是密切相关的黄病毒，ZIKV在东南亚国家接种过JEV的人群中流行。这提醒人们，对 JEV 的预先存在的免疫力会影响 ZIKV 感染和/或发病机制。在此我们表明，对 JEV SA14-14-2 疫苗接种的预先存在的免疫力为小鼠提供了针对非致死或致死剂量的 ZIKV 感染的充分保护。这与 JEV 抗体的被动免疫形成鲜明对比，后者未能影响小鼠的 ZIKV 感染或发病机制，尽管这些抗体在体外表现出 ZIKV 感染的交叉反应和抗体依赖性增强 (ADE) 。此外，我们确定 JEV 疫苗引发的 CD8 ⁺需要 T 细胞来介导 ZIKV 感染的异型保护，它与 ZIKV E 和 NS5 抗原（E _294-302和 NS5 _2839-2848）发生交叉反应。^{这些 CD8 +} T 细胞的过继转移可以部分保护小鼠免受 ZIKV 攻击。因此，尽管缺乏流行病学证据，但这些结果表明，由 JEV 疫苗接种激活的交叉反应性 CD8 ⁺ T 细胞可以保护人群中潜在的 ZIKV 感染。