Assessment of a vesicular stomatitis virus-based vaccine by use of the mouse model of Ebola virus hemorrhagic fever
Assessment of a vesicular stomatitis virus-based vaccine by use of the mouse model of Ebola virus hemorrhagic fever
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DOI：
10.1086/520591
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发表时间：
2007-11-15
影响因子：
6.4
通讯作者：
Feldmann, Heinz
中科院分区：
文献类型：
--
作者：
Jones, Steven M.;Stroeher, Ute;Feldmann, Heinz
背景在人类和非人类灵长类动物中，埃博拉病毒引起致命的病毒性出血热，目前还没有获得许可的疫苗或治疗药物。在本研究中，我们使用埃博拉出血热的小鼠模型来评估基于表达扎伊尔埃博拉病毒（ZEBOV）糖蛋白的减毒水泡性口炎病毒的疫苗的安全性和有效性。健康小鼠接种不同剂量的疫苗，从2 × 10（4）减少到2个空斑形成单位（pfu），采用全身和粘膜接种途径。用10（3）至10（6）致死剂量的小鼠适应性ZEBOV攻击小鼠。将2 × 10（5）pfu（比正常免疫剂量大10倍）注射到严重免疫功能低下的小鼠，以测试疫苗的安全性。两个空斑形成单位的疫苗保护免受致命的挑战，粘膜免疫被认为是作为全身注射的保护。在免疫动物中从未检测到复制型疫苗，免疫后也没有临床体征。用200，000 pfu的疫苗免疫严重免疫功能低下的小鼠未导致临床疾病。我们的数据表明，该疫苗是高度有效和安全的，它非常迅速地诱导小鼠的“无菌”免疫。如果在非人灵长类动物中得到证实，粘膜递送的潜力使其成为在爆发期间或在故意释放的情况下进行大规模免疫的极好候选者。
Background. In humans and nonhuman primates, Ebola virus causes a virulent viral hemorrhagic fever for which no licensed vaccines or therapeutic drugs exist. In the present study, we used the mouse model for Ebola hemorrhagic fever to assess the safety and efficacy of a vaccine based on a live attenuated vesicular stomatitis virus expressing the Zaire ebolavirus (ZEBOV) glycoprotein.Methods. Healthy mice were given the vaccine in various doses, decreasing from 2 X 10(4) to 2 plaque-forming units (pfu), with both systemic and mucosal vaccination routes used. Mice were challenged with to 10(3) to 10(6) lethal doses of mouse-adapted ZEBOV. Severely immunocompromised mice were injected with 2 X 10(5) pfu, which is 10 times greater than the immunization dose normally used, to test vaccine safety.Results. Two plaque-forming units of the vaccine protected against lethal challenge, and mucosal immunization was found to be as protective as systemic injection. The replicating vaccine was never detected in the immunized animals, nor were there clinical signs after immunization. Immunization of severely immunocompromised mice with 200,000 pfu of vaccine resulted in no clinical symptoms.Conclusions. Our data suggest that the vaccine is highly potent and safe and that it very rapidly induces "sterile" immunity in mice. The potential for mucosal delivery, if confirmed in nonhuman primates, makes it an excellent candidate for mass immunization during outbreaks or in the event of intentional release.