A live-attenuated Zika virus vaccine candidate induces sterilizing immunity in mouse models.
A live-attenuated Zika virus vaccine candidate induces sterilizing immunity in mouse models.
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DOI：
10.1038/nm.4322
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发表时间：
2017-06
期刊：
影响因子：
82.9
通讯作者：
Shi PY
中科院分区：
文献类型：
--
作者：
Shan C;Muruato AE;Nunes BTD;Luo H;Xie X;Medeiros DBA;Wakamiya M;Tesh RB;Barrett AD;Wang T;Weaver SC;Vasconcelos PFC;Rossi SL;Shi PY
寨卡病毒(Zika Virus，ZIKV)感染孕妇可引起多种先天性畸形(包括小头畸形)，现在统称为先天性ZIKV综合征。需要一种疫苗来预防或显著减轻孕妇和前往疫区/流行地区的旅行者的病毒血症，以避免先天性ZIKV综合征，并可能有助于抑制疫情传播。在这里，我们报道了一种在ZIKV基因组3‘非翻译区(10-del ZIKV)含有10个核苷酸缺失的减毒活疫苗候选。在A129小鼠模型中，10-del ZIKV具有高度减毒、免疫原性和保护性。关键的是，单剂10-del ZIKV诱导了高水平的中和抗体的无菌免疫，并完全防止了攻击后的病毒血症。免疫的小鼠也产生了强大的T细胞反应。用1×104IFU的10-del ZIKV脑内接种1日龄CD1小鼠，未发现可检测到的疾病，而用10IFU的野生型ZIKV感染则是致命的。在机制上，10-del ZIKV通过减少病毒RNA合成和增加对I型干扰素抑制的敏感性来减弱其毒力。减毒的10-del ZIKV在口服添加血粉后不能感染蚊子，这代表了在非流行地区使用的另一个安全特征。总而言之，安全性和有效性结果保证了这种有前途的减毒ZIKV候选疫苗的进一步开发。
Zika virus (ZIKV) infection of pregnant patients could cause a wide range of congenital abnormalities (including microcephaly) now collectively known as congenital ZIKV syndrome. A vaccine to prevent or significantly attenuate viremia in pregnant women and travelers to epidemic/endemic regions is needed to avert congenital ZIKV syndrome, and could also be useful to suppress epidemic transmission. Here we report a live-attenuated vaccine candidate that contains a 10-nucleotide deletion in the 3’ untranslated region of ZIKV genome (10-del ZIKV). The 10-del ZIKV is highly attenuated, immunogenic, and protective in the A129 mouse model. Critically, a single dose of 10-del ZIKV induced sterilizing immunity with a high level of neutralizing antibodies and completely prevented viremia after challenge. The immunized mice also developed a robust T cell response. Intracranial inoculation of one-day-old CD1 mice with 1×104 IFU of 10-del ZIKV caused no detectable disease, whereas infections with 10 IFU of wild-type ZIKV were lethal. Mechanistically, the 10-del ZIKV attenuated its virulence through decreased viral RNA synthesis and increased sensitivity to type-I interferon inhibition. The attenuated 10-del ZIKV was incompetent in infecting mosquitoes after oral feeding of spiked blood meals, representing an additional safety feature for use in non-endemic regions. Collectively, the safety and efficacy results warrant further development of this promising live-attenuated ZIKV vaccine candidate.
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影响因子：
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