Ebola virus-like particles protect from lethal Ebola virus infection
Ebola virus-like particles protect from lethal Ebola virus infection
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DOI：
10.1073/pnas.2237038100
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发表时间：
2003-12-23
影响因子：
11.1
通讯作者：
Bavari, S
中科院分区：
文献类型：
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作者：
Warfield, KL;Bosio, CM;Bavari, S
丝状病毒埃博拉会引起出血热，造成 70-80% 的人类死亡率。高的。病死率以及已知的气溶胶传染性使埃博拉病毒成为潜在的全球健康威胁和可能的生物战剂。开发用于自然疫情爆发、应对生物攻击和保护实验室工作人员的有效疫苗是比以往任何时候都更加重要的国家优先事项。埃博拉病毒糖蛋白（GP）和基质蛋白（VP40）在哺乳动物细胞中的共表达会导致病毒样颗粒（VLP）的自发产生和释放，这些颗粒类似于独特的丝状传染性病毒粒子。 VLP 已经过测试，发现作为多种病毒的疫苗是有效的，包括乳头瘤病毒、艾滋病毒、细小病毒和轮状病毒。在此，我们报道了埃博拉VLP（eVLP）在体外具有免疫原性，因为eVLF成熟并激活了小鼠骨髓来源的树突状细胞，通过细胞表面标志物CD40、CD80、CD86和MHC I和II类的增加以及树突状细胞分泌IL-6、IL-10、巨噬细胞炎症蛋白（MIP）-1α和肿瘤坏死因子a来评估。此外，给小鼠接种 eVLP 可以激活 CD4(+) 和 CD8(+) T 细胞以及 CD19(+) B 细胞。接种 eVLP 疫苗后，小鼠产生了高滴度的埃博拉病毒特异性抗体，包括中和抗体。重要的是，接种 eVLP 的小鼠可以 100% 免受致命的埃博拉病毒接种。总之，我们的数据表明，eVLP 代表了一种有前途的预防埃博拉病毒感染的候选疫苗，也是检查埃博拉病毒免疫反应的起源和性质急需的工具。
The filovirus Ebola causes hemorrhagic fever with 70-80% human mortality. High. case-fatality rates, as well as known aerosol infectivity, make Ebola virus a potential global health threat and possible biological warfare agent. Development of an effective vaccine for use in natural outbreaks, response to biological attack, and protection of laboratory workers is a higher national priority than ever before. Coexpression of the Ebola virus glycoprotein (GP) and matrix protein (VP40) in mammalian cells results in spontaneous production and release of virus-like particles (VLPs) that resemble the distinctively filamentous infectious virions. VLPs have been tested and found efficacious as vaccines for several viruses, including papillomavirus, HIV, parvovirus, and rotavirus. Herein, we report that Ebola VLPs (eVLPs) were immunogenic in vitro as eVLFs matured and activated mouse bone marrow-derived dendritic cells, assessed by increases in cell-surface markers CD40, CD80, CD86, and MHC class I and II and secretion of IL-6, IL-10, macrophage inflammatory protein (MIP)-1alpha, and tumor necrosis factor a by the dendritic cells. Further, vaccinating mice with eVLPs activated CD4(+) and CD8(+) T cells, as well as CD19(+) B cells. After vaccination with eVLPs, mice developed high titers of Ebola virus-specific antibodies, including neutralizing antibodies. Importantly, mice vaccinated with eVLPs were 100% protected from an otherwise lethal Ebola virus inoculation. Together, our data suggest that eVLPs represent a promising vaccine candidate for protection against Ebola virus infections and a much needed tool to examine the genesis and nature of immune responses to Ebola virus.