Human antibody response to Zika targets type-specific quaternary structure epitopes
Human antibody response to Zika targets type-specific quaternary structure epitopes
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DOI：
10.1172/jci.insight.124588
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发表时间：
2019-04-18
期刊：
影响因子：
8
通讯作者：
de Silva, Aravinda M.
中科院分区：
文献类型：
--
作者：
Collins, Matthew H.;Tu, Huy A.;de Silva, Aravinda M.
最近在美洲爆发的寨卡病毒（ZIKV）疫情显示出罕见但严重的感染表现。 ZIKV 已在登革热病毒 (DENV) 流行地区出现，登革热病毒是一种密切相关的蚊媒黄病毒。交叉反应抗体混淆了 ZIKV 流行病学和发病机制的研究。不同人对 ZIKV 的免疫反应可能有所不同，具体取决于他们的 DENV 免疫状态。在这里，我们重点关注作为原发性黄病毒感染的 ZIKV 的人类 B 细胞和抗体反应，以定义在缺乏对 DENV 的预先存在的免疫力的情况下产生的中和和保护性抗体的特性。血浆抗体和记忆 B 细胞反应具有高度 ZIKV 类型特异性，ZIKV 中和抗体主要针对病毒包膜上的四级结构表位。为了绘制保护性抗体靶向的病毒表位，我们从 ZIKV 病例中分离出 2 种类型特异性单克隆抗体 (mAb)。两种单克隆抗体在体外均具有强中和作用，在体内具有保护作用。 mAb 可识别以包膜蛋白结构域 I 和 II 为中心的不同表位。我们还证明，这些 mAb 的表位定义了来自 ZIKV 感染恢复的流行区和非流行区个体血浆抗体通常靶向的抗原区域。
The recent Zika virus (ZIKV) epidemic in the Americas has revealed rare but serious manifestations of infection. ZIKV has emerged in regions endemic for dengue virus (DENV), a closely related mosquito-borne flavivirus. Cross-reactive antibodies confound studies of ZIKV epidemiology and pathogenesis. The immune responses to ZIKV may be different in people, depending on their DENV immune status. Here, we focus on the human B cell and antibody response to ZIKV as a primary flavivirus infection to define the properties of neutralizing and protective antibodies generated in the absence of preexisting immunity to DENV. The plasma antibody and memory B cell response is highly ZIKV type-specific, and ZIKV-neutralizing antibodies mainly target quaternary structure epitopes on the viral envelope. To map viral epitopes targeted by protective antibodies, we isolated 2 type-specific monoclonal antibodies (mAbs) from a ZIKV case. Both mAbs were strongly neutralizing in vitro and protective in vivo. The mAbs recognize distinct epitopes centered on domains I and II of the envelope protein. We also demonstrate that the epitopes of these mAbs define antigenic regions commonly targeted by plasma antibodies in individuals from endemic and nonendemic regions who have recovered from ZIKV infections.