Emerging Viral Pathogens Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
J Virol. 2011 Oct;85(20):10605-16. doi: 10.1128/JVI.00558-11. Epub 2011 Aug 17.
The search for a safe and efficacious vaccine for Ebola virus continues, as no current vaccine candidate is nearing licensure. We have developed (i) replication-competent, (ii) replication-deficient, and (iii) chemically inactivated rabies virus (RABV) vaccines expressing Zaire Ebola virus (ZEBOV) glycoprotein (GP) by a reverse genetics system based on the SAD B19 RABV wildlife vaccine. ZEBOV GP is efficiently expressed by these vaccine candidates and is incorporated into virions. The vaccine candidates were avirulent after inoculation of adult mice, and viruses with a deletion in the RABV glycoprotein had greatly reduced neurovirulence after intracerebral inoculation in suckling mice. Immunization with live or inactivated RABV vaccines expressing ZEBOV GP induced humoral immunity against each virus and conferred protection from both lethal RABV and EBOV challenge in mice. The bivalent RABV/ZEBOV vaccines described here have several distinct advantages that may speed the development of inactivated vaccines for use in humans and potentially live or inactivated vaccines for use in nonhuman primates at risk of EBOV infection in endemic areas.
目前尚无接近许可的埃博拉病毒有效安全疫苗，因此，人们仍在继续寻找。我们利用基于 SAD B19 狂犬病病毒（RABV）野生动物疫苗的反向遗传学系统，开发了（i）复制型、（ii）复制缺陷型和（iii）化学灭活的狂犬病病毒（RABV）疫苗，可表达扎伊尔型埃博拉病毒（ZEBOV）糖蛋白（GP）。这些候选疫苗能有效地表达 ZEBOV GP，并将其纳入病毒粒子。候选疫苗在成年小鼠接种后无毒性，在幼鼠脑内接种缺失 RABV 糖蛋白的病毒后，其神经毒性大大降低。用表达 ZEBOV GP 的活疫苗或灭活疫苗免疫，可诱导针对每种病毒的体液免疫，并能保护小鼠免受致死性 RABV 和 EBOV 攻击。本文所述的二价 RABV/ZEBOV 疫苗具有几个明显的优势，可能会加快开发针对人类使用的灭活疫苗，以及针对流行地区有感染 EBOV 风险的非人类灵长类动物使用的活疫苗或灭活疫苗。
