Filovirus Laboratory, INSERM U758, Human Virology Department, Claude Bernard University Lyon-1, Université de Lyon, Ecole Normale Supérieure de Lyon, Lyon, France.
J Infect Dis. 2011 Nov;204 Suppl 3(Suppl 3):S1060-5. doi: 10.1093/infdis/jir347.
Pre- or postexposure treatments against the filoviral hemorrhagic fevers are currently not available for human use. We evaluated, in a guinea pig model, the immunogenic potential of Kunjin virus (KUN)-derived replicons as a vaccine candidate against Ebola virus (EBOV). Virus like particles (VLPs) containing KUN replicons expressing EBOV wild-type glycoprotein GP, membrane anchor-truncated GP (GP/Ctr), and mutated GP (D637L) with enhanced shedding capacity were generated and assayed for their protective efficacy. Immunization with KUN VLPs expressing full-length wild-type and D637L-mutated GPs but not membrane anchor-truncated GP induced dose-dependent protection against a challenge of a lethal dose of recombinant guinea pig-adapted EBOV. The surviving animals showed complete clearance of the virus. Our results demonstrate the potential for KUN replicon vectors as vaccine candidates against EBOV infection.
目前尚无针对丝状病毒出血热的暴露前或暴露后治疗方法。我们在豚鼠模型中评估了 Kunjin 病毒(KUN)衍生的复制子作为埃博拉病毒(EBOV)疫苗候选物的免疫原性。生成了含有 KUN 复制子的病毒样颗粒(VLPs),该复制子表达 EBOV 野生型糖蛋白 GP、膜锚截断 GP(GP/Ctr)和具有增强脱落能力的突变 GP(D637L),并对其保护效力进行了检测。用表达全长野生型和 D637L 突变型 GP 的 KUN VLPs 免疫,而不是用膜锚截断 GP 免疫,可诱导针对重组豚鼠适应型 EBOV 致死剂量的攻击的剂量依赖性保护。存活的动物完全清除了病毒。我们的结果表明 KUN 复制子载体有潜力成为针对 EBOV 感染的疫苗候选物。