Ebola virus glycoprotein Fc fusion protein confers protection against lethal challenge in vaccinated mice.
Ebola virus glycoprotein Fc fusion protein confers protection against lethal challenge in vaccinated mice.
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DOI：
10.1016/j.vaccine.2011.01.113
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发表时间：
2011-04-05
期刊：
影响因子：
5.5
通讯作者：
Kaplan, Gerardo G.
中科院分区：
文献类型：
--
作者：
Konduru, Krishnamurthy;Bradfute, Steven B.;Jacques, Jerome;Manangeeswaran, Mohanraj;Nakamura, Siham;Morshed, Sufi;Wood, Steven C.;Bavari, Sina;Kaplan, Gerardo G.
关键词：
埃博拉病毒是一种丝状病毒科病毒，可引起人类出血热并导致高发病率和死亡率。丝状病毒被归类为“A 类生物恐怖制剂”，目前尚无获得许可的疗法或疫苗来治疗和预防感染。丝状病毒糖蛋白（GP）足以保护个体免受感染，基于GP的多种疫苗正在开发中，包括重组腺病毒、副流感病毒、委内瑞拉马脑炎病毒、水泡性口炎病毒（VSV）和病毒样颗粒。在这里，我们描述了 GP Fc 融合蛋白作为候选疫苗的开发。我们在哺乳动物细胞中表达了与人 IgG1 Fc 片段 (ZEBOVGP-Fc) 融合的扎伊尔埃博拉病毒 (ZEBOV) GP 的胞外结构域，并表明 GP 经历了在天然膜结合 GP 中观察到的复杂的弗林蛋白酶裂解和加工。用ZEBOVGP-Fc免疫的小鼠产生了针对ZEBOV GP的T细胞免疫和针对具有复制能力的VSV-G删除的含有ZEBOV GP的重组VSV的中和抗体。接种 ZEBOVGP-Fc 疫苗的小鼠可免受致死剂量 ZEBOV 的攻击。这些结果表明，仅用ZEBOVGP-Fc融合蛋白进行疫苗接种，无需病毒载体或组装成病毒样颗粒，就足以在小鼠中诱导针对ZEBOV的保护性免疫。我们的数据表明，丝状病毒 GP Fc 融合蛋白可以开发为一种简单、安全、有效且具有成本效益的人类丝状病毒感染疫苗。
Ebola virus is a Filoviridae that causes hemorrhagic fever in humans and induces high morbidity and mortality rates. Filoviruses are classified as "Category A bioterrorism agents", and currently there are no licensed therapeutics or vaccines to treat and prevent infection. The Filovirus glycoprotein (GP) is sufficient to protect individuals against infection, and several vaccines based on GP are under development including recombinant adenovirus, parainfluenza virus, Venezuelan equine encephalitis virus, vesicular stomatitis virus (VSV) and virus-like particles. Here we describe the development of a GP Fc fusion protein as a vaccine candidate. We expressed the extracellular domain of the Zaire Ebola virus (ZEBOV) GP fused to the Fc fragment of human IgG1 (ZEBOVGP-Fc) in mammalian cells and showed that GP undergoes the complex furin cleavage and processing observed in the native membrane-bound GP. Mice immunized with ZEBOVGP-Fc developed T-cell immunity against ZEBOV GP and neutralizing antibodies against replication-competent VSV-G deleted recombinant VSV containing ZEBOV GP. The ZEBOVGP-Fc vaccinated mice were protected against challenge with a lethal dose of ZEBOV. These results show that vaccination with the ZEBOVGP-Fc fusion protein alone without the need of a viral vector or assembly into virus-like particles is sufficient to induce protective immunity against ZEBOV in mice. Our data suggested that Filovirus GP Fc fusion proteins could be developed as a simple, safe, efficacious, and cost effective vaccine against Filovirus infection for human use.
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影响因子：
3.3
作者：
Chen, Hongying;Xu, Xiaodong;Jones, Ian M.
通讯作者：
Jones, Ian M.
DOI：
10.1073/pnas.92.10.4477
发表时间：
1995-05-09
影响因子：
11.1
作者：
LAWSON, ND;STILLMAN, EA;ROSE, JK
通讯作者：
ROSE, JK
影响因子：
5.4
作者：
Hood, Chantelle L.;Abraham, Jonathan;Nabel, Gary J.
通讯作者：
Nabel, Gary J.
影响因子：
5.4
作者：
Bukreyev, Alexander;Rollin, Pierre E.;Sanchez, Anthony
通讯作者：
Sanchez, Anthony
影响因子：
6.7
作者：
Geisbert, Thomas W.;Daddario-DiCaprio, Kathleen M.;Jahrling, Peter B.
通讯作者：
Jahrling, Peter B.