Development of recombinant vaccine for lassa fever using replication-incompetent rabies viral vector.

拉沙热是一种急性病毒性疾病，目前还没有有效的候选疫苗。据报道，细胞免疫在预防拉沙热中起主要作用。无复制能力的活病毒疫苗将是拉沙热有希望的候选疫苗。为评价无复制能力的弹状病毒载体用于拉沙热疫苗的免疫原性，我们构建了缺失狂犬病病毒P基因、基因组中含有淋巴细胞性脉络丛脑膜炎病毒（LCMV）GPC基因的重组狂犬病病毒--delta-P-GPC株。我们用免疫荧光法和western blot法证实了在delta-P-GPC株感染的表达狂犬病P蛋白的BHK细胞中GPC蛋白的表达。80%的小鼠通过i.m.和i. p.途径，抵抗LCMV WE株的致死性攻击存活。

Lassa fever is an acute viral illness, and there is no effective vaccine candidate available. It has been reported that cellular immunity plays the major roles in the prevention against lassa fever. Replication-incompetent live viral vaccine would be a promising vaccine candidate for lassa fever. To evaluate the immunogenicity of the replication-incompetent rhabdovirus vector for vaccine against lassa fever, we newly generated the recombinant rabies virus, delta-P-GPC strain, which lacks rabies P gene and possesses lymphocytic choriomeningitis virus (LCMV) GPC gene in its genome. We confirmed the GPC protein expression in delta-P-GPC strain infected rabies P protein expressing BHK cells by immunofluorescence assay and western blot. 80% of mice immunized twice with delta-P-GPC by i.m. and i.p. route, survived against lethal challenge with LCMV WE strain.