Vaccine protection against Zika virus from Brazil.
Vaccine protection against Zika virus from Brazil.
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DOI：
10.1038/nature18952
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发表时间：
2016-08-25
期刊：
影响因子：
64.8
通讯作者：
Barouch, Dan H.
中科院分区：
文献类型：
--
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.
寨卡病毒(ZIKV)是一种黄病毒，目前在巴西和美洲引发了前所未有的疫情。ZIKV与人类和小鼠的胎儿小头畸形、宫内生长受限和其他出生缺陷有因果关系。快速开发安全有效的ZIKV疫苗是全球卫生优先事项，但目前对ZIKV免疫学和免疫保护机制知之甚少。在这里，我们表明，对来自巴西东北部的ZIKV暴发毒株的攻击，一次免疫质粒DNA疫苗或纯化的灭活病毒疫苗可为易感小鼠提供完全保护。这种ZIKV毒株最近被证明可以穿过胎盘，并在小鼠中导致胎儿小头畸形和其他先天性畸形。我们制备了表达ZIKV全长前膜和包膜的DNA疫苗(PRM-Env)以及一系列缺失突变体。全长PRM-Env DNA疫苗，而不是缺失突变体，提供了对ZIKV的完全保护，这是因为攻击后没有检测到病毒血症，保护效果与Env特异性抗体效价相关。过继转移免疫小鼠纯化的免疫球蛋白具有被动保护作用，而免疫小鼠体内的CD4和CD8T淋巴细胞缺失并不能消除免疫保护作用。这些数据表明，单次注射亚单位疫苗和灭活病毒疫苗可以在小鼠中实现对ZIKV攻击的保护，环境特异性抗体效价是保护的关键免疫学相关因素。我们的发现表明，为人类开发ZIKV疫苗很可能是容易实现的。
Zika virus (ZIKV) is a flavivirus that is responsible for an unprecedented current epidemic in Brazil and the Americas. ZIKV has been causally associated with fetal microcephaly, intrauterine growth restriction, and other birth defects in both humans and mice. The rapid development of a safe and effective ZIKV vaccine is a global health priority, but very little is currently known about ZIKV immunology and mechanisms of immune protection. Here we show that a single immunization of a plasmid DNA vaccine or a purified inactivated virus vaccine provides complete protection in susceptible mice against challenge with a ZIKV outbreak strain from northeast Brazil. This ZIKV strain has recently been shown to cross the placenta and to induce fetal microcephaly and other congenital malformations in mice. We produced DNA vaccines expressing full-length ZIKV pre-membrane and envelope (prM-Env) as well as a series of deletion mutants. The full-length prM-Env DNA vaccine, but not the deletion mutants, afforded complete protection against ZIKV as measured by absence of detectable viremia following challenge, and protective efficacy correlated with Env-specific antibody titers. Adoptive transfer of purified IgG from vaccinated mice conferred passive protection, and CD4 and CD8 T lymphocyte depletion in vaccinated mice did not abrogate protective efficacy. These data demonstrate that protection against ZIKV challenge can be achieved by single-shot subunit and inactivated virus vaccines in mice and that Env-specific antibody titers represent key immunologic correlates of protection. Our findings suggest that the development of a ZIKV vaccine for humans will likely be readily achievable.
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DOI：
10.1126/science.aaf5036
发表时间：
2016-04-15
期刊：
Science (New York, N.Y.)
影响因子：
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