Plana-Duran J, Bastons M, Rodriguez M J, Climent I, Cortés E, Vela C, Casal I
Laboratorios Sobrino-Cyanamid, Vall de Bianya, Madrid, Spain.
Arch Virol. 1996;141(8):1423-36. doi: 10.1007/BF01718245.
Rabbit hemorrhagic disease virus (RHDV) causes more than 90% mortality in adult rabbits. In this study, the cDNA of the VP60 coding sequence of RHDV was cloned under the control of the polyhedrin and p10 promoters of baculovirus to be expressed in insect cells. The expression of RHDV VP60 under the control of the p10 promoter was 5-10 times higher than using the polyhedrin promoter. The p10-derived VP60 was able to assemble into virus-like particles (VLPs). RHDV VLPs were successfully used to protect rabbits against the disease even at doses as low as 0.5 micrograms when injected intramuscularly or subcutaneously. The ability to elicit an immune response was independent of the adjuvant or the route of immunization. Remarkably, oral administration of RHDV VLPs efficiently induced protecting antibodies to RHD at doses as low as 3 micrograms. The use of binary ethylenimine for the stabilization of the VLPs was decisive for eliciting a good oral immunity. This report demonstrates the potential use of these procapsids in obtaining RHD oral vaccines and opens the door to the use of these capsids for the prevention of the disease in wild animals. Therefore, a new, and potentially important application of recombinant VLPs in the induction of protective immunity by the oral route is foreseen.
兔出血症病毒（RHDV）可导致90%以上的成年兔死亡。在本研究中，RHDV的VP60编码序列的cDNA在杆状病毒的多角体蛋白和p10启动子控制下进行克隆，以便在昆虫细胞中表达。在p10启动子控制下RHDV VP60的表达比使用多角体蛋白启动子高5至10倍。源自p10的VP60能够组装成病毒样颗粒（VLP）。即使以低至0.5微克的剂量肌肉注射或皮下注射，RHDV VLP也成功用于保护兔子免受该疾病侵害。引发免疫反应的能力与佐剂或免疫途径无关。值得注意的是，口服低至3微克剂量的RHDV VLP能有效诱导针对兔出血症的保护性抗体。使用双乙撑亚胺稳定VLP对于引发良好的口服免疫起决定性作用。本报告证明了这些原衣壳在获得兔出血症口服疫苗方面的潜在用途，并为使用这些衣壳预防野生动物疾病打开了大门。因此，预计重组VLP在通过口服途径诱导保护性免疫方面将有新的、潜在重要的应用。
