Recombinant RNA replicons derived from attenuated Venezuelan equine encephalitis virus protect guinea pigs and mice from Ebola hemorrhagic fever virus
Recombinant RNA replicons derived from attenuated Venezuelan equine encephalitis virus protect guinea pigs and mice from Ebola hemorrhagic fever virus
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DOI：
10.1016/s0264-410x(00)00113-4
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发表时间：
2000-08-15
期刊：
影响因子：
5.5
通讯作者：
Smith, JF
中科院分区：
文献类型：
--
作者：
Pushko, P;Bray, M;Smith, JF
从甲病毒委内瑞拉马脑炎病毒（VEE）减毒株衍生的RNA复制子被配置为埃博拉出血热的候选疫苗。埃博拉核蛋白（NP）或糖蛋白（GP）基因被引入VEE 26S启动子下游的VEE RNA中，取代VEE结构蛋白基因。将表达NP或GP基因的重组复制子包装到VEE复制子颗粒（分别为NP- vrp和GP- vrp）中，使用双侧辅助系统提供反式VEE结构蛋白，并在包装过程中阻止复制能力VEE的再生。在BALB/c小鼠和两株豚鼠中评价了NP-VRP和GP-VRP的免疫原性及其对埃博拉致死性感染的保护能力。GP-VRP单独或与NP-VRP联合免疫对豚鼠和BALB/c小鼠均有保护作用，而NP-VRP单独免疫对BALB/c小鼠均无保护作用。被动转移vrp免疫动物的血清对致命攻击没有保护作用。然而，VRP主动免疫所实现的完全保护，以及VEE复制子载体的独特特性，有必要在灵长类动物中进一步测试NP-VRP和GP-VRP作为埃博拉出血热候选疫苗的安全性和有效性。Elsevier Science Ltd.出版。
RNA replicons derived from an attenuated strain of Venezuelan equine encephalitis virus (VEE), an alphavirus, were configured as candidate vaccines for Ebola hemorrhagic fever. The Ebola nucleoprotein (NP) or glycoprotein (GP) genes were introduced into the VEE RNA downstream from the VEE 26S promoter in place of the VEE structural protein genes. The resulting recombinant replicons, expressing the NP or GP genes, were packaged into VEE replicon particles(NP-VRP and GP-VRP, respectively) using a bipartite helper system that provided the VEE structural proteins in trans and prevented the regeneration of replication-competent VEE during packaging. The immunogenicity of NP-VRP and GP-VRP and their ability to protect against lethal Ebola infection were evaluated in BALB/c mice and in two strains of guinea pigs. The GP-VRP alone, or in combination with NP-VRP, protected both strains of guinea pigs and BALB/c mice, while immunization with NP-VRP alone protected BALB/c mice, but neither strain of guinea pig. Passive transfer of sera from VRP-immunized animals did not confer protection against lethal challenge. However, the complete protection achieved with active immunization with VRP, as well as the unique characteristics of the VEE replicon vector, warrant further testing of the safety and efficacy of NP-VRP and GP-VRP in primates as candidate vaccines against Ebola hemorrhagic fever. Published by Elsevier Science Ltd.