Geisbert Thomas W, Daddario-Dicaprio Kathleen M, Geisbert Joan B, Reed Douglas S, Feldmann Friederike, Grolla Allen, Ströher Ute, Fritz Elizabeth A, Hensley Lisa E, Jones Steven M, Feldmann Heinz
National Emerging Infectious Diseases Laboratories Institute, Boston University School of Medicine, Boston, MA, USA.
Vaccine. 2008 Dec 9;26(52):6894-900. doi: 10.1016/j.vaccine.2008.09.082. Epub 2008 Oct 18.
Considerable progress has been made over the last decade in developing candidate preventive vaccines that can protect nonhuman primates against Ebola and Marburg viruses. A vaccine based on recombinant vesicular stomatitis virus (VSV) seems to be particularly robust as it can also confer protection when administered as a postexposure treatment. While filoviruses are not thought to be transmitted by aerosol in nature the inhalation route is among the most likely portals of entry in the setting of a bioterrorist event. At present, all candidate filoviral vaccines have been evaluated against parenteral challenges but none have been tested against an aerosol exposure. Here, we evaluated our recombinant VSV-based Zaire ebolavirus (ZEBOV) and Marburg virus (MARV) vaccines against aerosol challenge in cynomolgus macaques. All monkeys vaccinated with a VSV vector expressing the glycoprotein of ZEBOV were completely protected against an aerosol exposure of ZEBOV. Likewise, all monkeys vaccinated with a VSV vector expressing the glycoprotein of MARV were completely protected against an aerosol exposure of MARV. All control animals challenged by the aerosol route with either ZEBOV or MARV succumbed. Interestingly, disease in control animals appeared to progress slower than previously seen in macaques exposed to comparable doses by intramuscular injection.
在过去十年中,在开发能够保护非人灵长类动物免受埃博拉病毒和马尔堡病毒感染的候选预防性疫苗方面取得了相当大的进展。一种基于重组水泡性口炎病毒(VSV)的疫苗似乎特别有效,因为它在暴露后治疗时也能提供保护。虽然丝状病毒在自然情况下不被认为是通过气溶胶传播的,但在生物恐怖事件中,吸入途径是最有可能的进入门户之一。目前,所有候选丝状病毒疫苗都已针对肠胃外攻击进行了评估,但没有一种针对气溶胶暴露进行过测试。在这里,我们在食蟹猕猴中评估了我们基于重组VSV的扎伊尔埃博拉病毒(ZEBOV)和马尔堡病毒(MARV)疫苗对气溶胶攻击的效果。所有接种表达ZEBOV糖蛋白的VSV载体疫苗的猴子都完全受到保护,免受ZEBOV气溶胶暴露的影响。同样,所有接种表达MARV糖蛋白的VSV载体疫苗的猴子都完全受到保护,免受MARV气溶胶暴露的影响。所有通过气溶胶途径用ZEBOV或MARV攻击的对照动物都死亡了。有趣的是,对照动物中的疾病进展似乎比以前在通过肌肉注射接触相当剂量病毒的猕猴中看到的要慢。