Japanese Encephalitis Vaccine Generates Cross-Reactive Memory T Cell Responses to Zika Virus in Humans.

Japanese Encephalitis Vaccine Generates Cross-Reactive Memory T Cell Responses to Zika Virus in Humans.
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DOI:
10.1155/2022/8379286
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发表时间:
2022
影响因子:
2.2
通讯作者:
Xie, Zhengde
Xie, Zhengde
中科院分区:
医学4区
文献类型:
--
作者:
Wang, Ran;Zhang, Meng;Zhang, Linlin;Liu, Mengjia;Shan, Chao;An, Jing;Xie, Zhengde

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寨卡病毒(ZIKV)和日本脑炎病毒(JEV)是具有序列同源性的蚊媒黄病毒。ZIKV在JEV也传播的一些地区传播,或者在使用JE疫苗接种的地区传播。黄病毒之间存在交叉免疫,但确切的机制尚不清楚。我们先前证明,由减毒活日本脑炎(JE)SA 14 -14-2疫苗诱导的T细胞免疫赋予小鼠针对ZIKV感染的保护性免疫,这甚至可以绕过抗体依赖性增强。然而,T细胞免疫,特别是记忆T细胞亚群在人类中JE疫苗和ZIKV之间的交叉反应性免疫应答中的作用尚未报道。 我们分别检测了JEV和ZIKV存在下的中枢和效应记忆CD 4+和CD 8 + T细胞(TCM和TEM)应答(包括脱粒、细胞因子和趋化因子),方法是使用来自18名最近接受过两剂疗程JE疫苗SA 14 -14-2的儿童以及7名未接种JE疫苗的儿童的合格外周血单核细胞样本。 响应于ZIKV的交叉反应性CD 8 + TCM的特征在于分泌IFN-γ,而CD 8 + TEM未显示功能因子的显著上调。在ZIKV存在的情况下,CD 4 + TEM上调了IFN-γ和TNF-α的表达,并且CD 4 + TCM的表达特征更具细胞毒性潜力。 我们分析了JE疫苗接受者中对ZIKV的交叉反应性记忆T细胞应答。这些数据将为JEV和ZIKV之间的交叉反应性记忆T细胞免疫应答机制提供证据,并为二价疫苗设计策略提供更精细的观点。
Zika virus (ZIKV) and Japanese encephalitis virus (JEV) are mosquito-borne flaviviruses with sequence homology. ZIKV circulates in some regions where JEV also circulates, or where JE vaccination is used. Cross-immunity between flaviviruses exists, but the precise mechanisms remain unclear. We previously demonstrated that T cell immunity induced by the live-attenuated Japanese encephalitis (JE) SA14-14-2 vaccine conferred protective immunity against ZIKV infection in mice, which could even bypass antibody-dependent enhancement. However, the role of T cell immune, especially memory T cell subsets, in cross-reactive immune responses between JE vaccine and ZIKV in humans has not been reported. We examined central and effector memory CD4+ and CD8+ T cell (TCM and TEM) responses (including degranulation, cytokines, and chemokines) in the presence of JEV and ZIKV, respectively, by using qualified peripheral blood mononuclear cell samples from 18 children who had recently received a two-dose course of JE vaccine SA14-14-2 as well as seven children without JE vaccination. Cross-reactive CD8+ TCM in response to ZIKV was characterized by secretion of IFN-γ, whereas CD8+ TEM did not show significant upregulation of functional factors. In the presence of ZIKV, IFN-γ and TNF-α expression was upregulated by CD4+ TEM, and the expression signature of CD4+ TCM is more cytotoxic potential. We profiled the cross-reactive memory T cell responses to ZIKV in JE vaccine recipients. These data will provide evidence for the mechanism of cross-reactive memory T cell immune responses between JEV and ZIKV and a more refined view of bivalent vaccine design strategy.
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