A recombinant VSV-vectored MERS-CoV vaccine induces neutralizing antibody and T cell responses in rhesus monkeys after single dose immunization.
A recombinant VSV-vectored MERS-CoV vaccine induces neutralizing antibody and T cell responses in rhesus monkeys after single dose immunization.
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DOI：
10.1016/j.antiviral.2017.12.007
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发表时间：
2018-03
影响因子：
7.6
通讯作者：
Bu Z
中科院分区：
文献类型：
--
作者：
Liu R;Wang J;Shao Y;Wang X;Zhang H;Shuai L;Ge J;Wen Z;Bu Z
中东呼吸综合征冠状病毒（MERS-CoV）自2012年爆发以来一直是一种高度威胁的人畜共患病原体。与SARS-CoV类似，MERS-CoV属于冠状病毒家族，可在人类中引起严重的呼吸道症状，根据世界卫生组织的数据，平均病死率为35%。MERS-CoV S蛋白具有免疫原性，可诱导产生中和抗体，是疫苗开发的重要靶点。本研究以水泡性口炎病毒（VSV）为基础，将其G基因替换为MERS-CoV S基因，构建了一种嵌合病毒（VSVΔG-MERS）。S蛋白有效地整合到病毒包膜中，并通过结合其受体人DPP 4介导细胞进入。通过siRNA敲低网格蛋白表达显著消除了VSVΔG-MERS在Vero细胞中的感染。此外，在动物研究中，重组病毒在单次肌内或鼻内免疫剂量后在恒河猴中诱导中和抗体和T细胞应答。我们的研究结果表明嵌合VSVΔG-MERS作为针对新兴MERS-CoV疾病的快速应答疫苗候选物的潜力。构建表达MERS-CoV S基因的VSV嵌合病毒。嵌合病毒改变了进入模式，需要DPP 4作为其受体。嵌合病毒在猴子中诱导中和抗体和T细胞应答。
Middle East respiratory syndrome coronavirus (MERS-CoV) has been a highly threatening zoonotic pathogen since its outbreak in 2012. Similar to SARS-CoV, MERS-CoV belongs to the coronavirus family and can induce severe respiratory symptoms in humans, with an average case fatality rate of 35% according to the World Health Organization. Spike (S) protein of MERS-CoV is immunogenic and can induce neutralizing antibodies, thus is a potential major target for vaccine development. Here we constructed a chimeric virus based on the vesicular stomatitis virus (VSV) in which the G gene was replaced by MERS-CoV S gene (VSVΔG-MERS). The S protein efficiently incorporated into the viral envelope and mediated cell entry through binding its receptor, human DPP4. Knockdown of clathrin expression by siRNA drastically abrogated the infection of VSVΔG-MERS in Vero cells. Furthermore, in animal studies, the recombinant virus induced neutralizing antibodies and T cell responses in rhesus monkeys after a single intramuscular or intranasal immunization dose. Our findings indicate the potential of the chimeric VSVΔG-MERS as a rapid response vaccine candidate against emerging MERS-CoV disease. Constructing two chimeric virus based on VSV which express MERS-CoV S gene. The chimeric virus changed the entry mode and required DPP4 as its receptor. The chimeric virus induced neutralizing antibodies and T cell responses in monkeys.
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DOI：
10.1038/nrmicro.2016.81
发表时间：
2016-08
期刊：
Nature reviews. Microbiology
影响因子：
--
作者：
de Wit E;van Doremalen N;Falzarano D;Munster VJ
通讯作者：
Munster VJ
影响因子：
3.7
作者：
Kong, Dongni;Wen, Zhiyuan;Bu, Zhigao
通讯作者：
Bu, Zhigao
影响因子：
6.7
作者：
Falzarano D;de Wit E;Feldmann F;Rasmussen AL;Okumura A;Peng X;Thomas MJ;van Doremalen N;Haddock E;Nagy L;LaCasse R;Liu T;Zhu J;McLellan JS;Scott DP;Katze MG;Feldmann H;Munster VJ
通讯作者：
Munster VJ
DOI：
10.1073/pnas.1407087111
发表时间：
2014-10-21
影响因子：
11.1
作者：
Millet, Jean Kaoru;Whittaker, Gary R.
通讯作者：
Whittaker, Gary R.
影响因子：
5.4
作者：
Jaume, Martial;Yip, Ming S.;Peiris, J. S. Malik
通讯作者：
Peiris, J. S. Malik