Successful topical respiratory tract immunization of primates against ebola virus
Successful topical respiratory tract immunization of primates against ebola virus
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DOI：
10.1128/jvi.00105-07
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发表时间：
2007-06-01
影响因子：
5.4
通讯作者：
Sanchez, Anthony
中科院分区：
文献类型：
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作者：
Bukreyev, Alexander;Rollin, Pierre E.;Sanchez, Anthony
埃博拉病毒引起严重病毒性出血热暴发，人类死亡率高。该病毒具有高度传染性，可通过接触和气溶胶途径传播。这些特征使埃博拉病毒成为生物恐怖主义和生物战的潜在武器。因此，在呼吸道中诱导全身和局部免疫反应的疫苗将是非常有益的。我们评估了一种常见的儿童呼吸道病原体，人类副流感病毒3型（HPIV3），作为埃博拉病毒的疫苗载体。将表达埃博拉病毒（扎伊尔种）表面糖蛋白（GP）的HPIV3重组体单独或与核衣壳蛋白NP或细胞因子辅助粒细胞-巨噬细胞集落刺激因子联合使用，通过呼吸道途径给予感染HPIV3的恒河猴，评估其免疫原性和对埃博拉病毒腹腔内高致命性攻击的保护效果。任何表达GP结构的单次免疫对埃博拉病毒具有中等免疫原性，保护88%的动物免受埃博拉病毒引起的严重出血热和死亡。两剂具有高度免疫原性，所有动物都在攻击中存活下来，没有疾病迹象和可检测到的埃博拉病毒攻击病毒。这些数据说明了通过呼吸道免疫预防埃博拉病毒引起的出血热的可行性。据我们所知，这是第一个通过呼吸道局部免疫在灵长类动物模型中预防病毒性出血热感染的研究。
Ebola virus causes outbreaks of severe viral hemorrhagic fever with high mortality in humans. The virus is highly contagious and can be transmitted by contact and by the aerosol route. These features make Ebola virus a potential weapon for bioterrorism and biological warfare. Therefore, a vaccine that induces both systemic and local immune responses in the respiratory tract would be highly beneficial. We evaluated a common pediatric respiratory pathogen, human parainfluenza virus type 3 (HPIV3), as a vaccine vector against Ebola virus. HPIV3 recombinants expressing the Ebola virus (Zaire species) surface glycoprotein (GP) alone or in combination with the nucleocapsid protein NP or with the cytokine adjuvant granulocyte-macrophage colony-stimulating factor were administered by the respiratory route to rhesus monkeys-in which HPIV3 infection is mild and asymptomatic-and were evaluated for immunogenicity and protective efficacy against a highly lethal intraperitoneal challenge with Ebola virus. A single immunization with any construct expressing GP was moderately immunogenic against Ebola virus and protected 88% of the animals against severe hemorrhagic fever and death caused by Ebola virus. Two doses were highly immunogenic, and all of the animals survived challenge and were free of signs of disease and of detectable Ebola virus challenge virus. These data illustrate the feasibility of immunization via the respiratory tract against the hemorrhagic fever caused by Ebola virus. To our knowledge, this is the first study in which topical immunization through respiratory tract achieved prevention of a viral hemorrhagic fever infection in a primate model.