In vivo protection against ZIKV infection and pathogenesis through passive antibody transfer and active immunisation with a prMEnv DNA vaccine.
In vivo protection against ZIKV infection and pathogenesis through passive antibody transfer and active immunisation with a prMEnv DNA vaccine.
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DOI：
10.1038/npjvaccines.2016.21
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发表时间：
2016
期刊：
影响因子：
9.2
通讯作者：
Weiner DB
中科院分区：
文献类型：
--
作者：
Muthumani K;Griffin BD;Agarwal S;Kudchodkar SB;Reuschel EL;Choi H;Kraynyak KA;Duperret EK;Keaton AA;Chung C;Kim YK;Booth SA;Racine T;Yan J;Morrow MP;Jiang J;Lee B;Ramos S;Broderick KE;Reed CC;Khan AS;Humeau L;Ugen KE;Park YK;Maslow JN;Sardesai NY;Joseph Kim J;Kobinger GP;Weiner DB
由于蚊子传播的寨卡病毒（ZIKV）引起的感染和疾病在全球迅速蔓延，引起了人们的严重关切。最近的研究表明，ZIKV也可以通过性传播，进一步增加了这种病毒的暴露风险。与这种传播相关的是ZIKV感染母亲的婴儿中小头畸形和其他先天性异常病例的急剧增加，以及感染成人中格林巴利综合征的发生率上升。重要的是，没有针对ZIKV感染的许可疗法或疫苗。在这项研究中，我们产生并评估了靶向ZIKV的前膜+包膜蛋白（prME）的新型合成DNA疫苗的体内功效。在质粒构建体的初始体外开发和评估研究之后，通过电穿孔介导的增强的DNA递送，用这种基于prME DNA的免疫原免疫小鼠和非人灵长类动物。发现接种疫苗的动物产生抗原特异性细胞和体液免疫以及中和活性。在缺乏干扰素（IFN）-α/β受体（命名为IFNAR−/−）的小鼠中，用这种DNA疫苗免疫诱导，在体内病毒攻击后，除了防止脑组织中的病毒病理外，还可100%防止感染相关的体重减轻或死亡。此外，非人灵长类动物抗ZIKV免疫血清的被动转移保护了IFNAR−/−小鼠免受随后的病毒攻击。在NHP和致病性小鼠模型中的这项研究支持靶向prME的免疫应答在ZIKV感染中的重要性，并表明对这种疫苗方法的额外研究可能与人类的ZIKV控制和疾病预防相关。
Significant concerns have been raised owing to the rapid global spread of infection and disease caused by the mosquito-borne Zika virus (ZIKV). Recent studies suggest that ZIKV can also be transmitted sexually, further increasing the exposure risk for this virus. Associated with this spread is a dramatic increase in cases of microcephaly and additional congenital abnormalities in infants of ZIKV-infected mothers, as well as a rise in the occurrence of Guillain Barre’ syndrome in infected adults. Importantly, there are no licensed therapies or vaccines against ZIKV infection. In this study, we generate and evaluate the in vivo efficacy of a novel, synthetic, DNA vaccine targeting the pre-membrane+envelope proteins (prME) of ZIKV. Following initial in vitro development and evaluation studies of the plasmid construct, mice and non-human primates were immunised with this prME DNA-based immunogen through electroporation-mediated enhanced DNA delivery. Vaccinated animals were found to generate antigen-specific cellular and humoral immunity and neutralisation activity. In mice lacking receptors for interferon (IFN)-α/β (designated IFNAR−/−) immunisation with this DNA vaccine induced, following in vivo viral challenge, 100% protection against infection-associated weight loss or death in addition to preventing viral pathology in brain tissue. In addition, passive transfer of non-human primate anti-ZIKV immune serum protected IFNAR−/− mice against subsequent viral challenge. This study in NHP and in a pathogenic mouse model supports the importance of immune responses targeting prME in ZIKV infection and suggests that additional research on this vaccine approach may have relevance for ZIKV control and disease prevention in humans.
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影响因子：
64.8
作者：
Larocca, Rafael A.;Abbink, Peter;Peron, Jean Pierre S.;Zanotto, Paolo M. de A.;Iampietro, M. Justin;Badamchi-Zadeh, Alexander;Boyd, Michael;Ng'ang'a, David;Kirilova, Marinela;Nityanandam, Ramya;Mercado, Noe B.;Li, Zhenfeng;Moseley, Edward T.;Bricault, Christine A.;Borducchi, Erica N.;Giglio, Patricia B.;Jetton, David;Neubauer, George;Nkolola, Joseph P.;Maxfield, Lori F.;De La Barrera, Rafael A.;Jarman, Richard G.;Eckels, Kenneth H.;Michael, Nelson L.;Thomas, Stephen J.;Barouch, Dan H.
通讯作者：
Barouch, Dan H.
DOI：
10.1016/s0140-6736(15)00239-1
发表时间：
2015-11-21
期刊：
Lancet (London, England)
影响因子：
--
作者：
Trimble CL;Morrow MP;Kraynyak KA;Shen X;Dallas M;Yan J;Edwards L;Parker RL;Denny L;Giffear M;Brown AS;Marcozzi-Pierce K;Shah D;Slager AM;Sylvester AJ;Khan A;Broderick KE;Juba RJ;Herring TA;Boyer J;Lee J;Sardesai NY;Weiner DB;Bagarazzi ML
通讯作者：
Bagarazzi ML
DOI：
10.1038/mtna.2012.1
发表时间：
2012-02-14
期刊：
Molecular therapy. Nucleic acids
影响因子：
--
作者：
通讯作者：
--
DOI：
10.4269/ajtmh.16-0111
发表时间：
2016-06-01
期刊：
The American journal of tropical medicine and hygiene
影响因子：
--
作者：
Rossi SL;Tesh RB;Azar SR;Muruato AE;Hanley KA;Auguste AJ;Langsjoen RM;Paessler S;Vasilakis N;Weaver SC
通讯作者：
Weaver SC
DOI：
10.1126/science.aah6157
发表时间：
2016-09-09
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Abbink P;Larocca RA;De La Barrera RA;Bricault CA;Moseley ET;Boyd M;Kirilova M;Li Z;Ng'ang'a D;Nanayakkara O;Nityanandam R;Mercado NB;Borducchi EN;Agarwal A;Brinkman AL;Cabral C;Chandrashekar A;Giglio PB;Jetton D;Jimenez J;Lee BC;Mojta S;Molloy K;Shetty M;Neubauer GH;Stephenson KE;Peron JP;Zanotto PM;Misamore J;Finneyfrock B;Lewis MG;Alter G;Modjarrad K;Jarman RG;Eckels KH;Michael NL;Thomas SJ;Barouch DH
通讯作者：
Barouch DH