Yarosh O K, Wandeler A I, Graham F L, Campbell J B, Prevec L
Department of Biology, McMaster University, Hamilton, ON, Canada.
Vaccine. 1996 Sep;14(13):1257-64. doi: 10.1016/s0264-410x(96)00012-6.
The prevalence of wildlife rabies throughout the world and the continued spread of this disease in North America highlights the need for oral vaccines which may be used safely and effectively to vaccinate a number of species that are reservoirs or vectors of rabies. We have previously shown that AdRG1, a replication competent recombinant human adenovirus type 5 (Ad5) expressing a rabies glycoprotein (RG), can induce immunity to rabies in rodent, canine, and skunk model systems. To improve the Ad5 vector system as a potential oral vaccine, we have constructed additional Ad5 recombinant vectors and compared RG expression in cell culture and immunogenicity in animals. Two new replication competent vectors are compared. AdRG1.3, which carries RG with accompanying SV40 poly A addition sequences within an E3 deletion, and AdRG4, which has RG in the E3 deletion but under the control of an exogenous Ad2 major late promoter, both express higher levels of RG in permissive cell culture than did AdRG1 and both elicit high levels of serum anti-rabies antibodies by parenteral or oral routes in animals. AdRG1.3 may be a more effective vaccine vector in species which are non-permissive for the replication of human Ad5.
野生动物狂犬病在全球的流行以及该疾病在北美的持续传播凸显了口服疫苗的必要性，这种疫苗可安全有效地用于为多种作为狂犬病宿主或传播媒介的物种进行接种。我们之前已经表明，AdRG1是一种表达狂犬病糖蛋白（RG）的具有复制能力的重组人5型腺病毒（Ad5），它能在啮齿动物、犬类和臭鼬模型系统中诱导产生对狂犬病的免疫力。为了改进Ad5载体系统作为一种潜在的口服疫苗，我们构建了额外的Ad5重组载体，并比较了它们在细胞培养中的RG表达以及在动物体内的免疫原性。对两种新的具有复制能力的载体进行了比较。AdRG1.3在E3缺失区域携带RG并伴有SV40聚腺苷酸添加序列，AdRG4在E3缺失区域有RG但受外源Ad2主要晚期启动子的控制，二者在允许性细胞培养中表达的RG水平均高于AdRG1，并且通过肠胃外或口服途径在动物体内均能引发高水平的血清抗狂犬病抗体。在对人Ad5复制不允许的物种中，AdRG1.3可能是一种更有效的疫苗载体。
