ORAL IMMUNIZATION OF RABBITS WITH VP60 PARTICLES CONFERS PROTECTION AGAINST RABBIT HEMORRHAGIC-DISEASE

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 promot ers 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 a ssemble into virus-like particles (VLPs). RHDV VLPs were successfully used to protect rabbits against the disease even at doses as low as 0. 5 mu g when injected intramuscularly or sub-cutaneously. The ability t o elicit an immune response was independent of the adjuvant or the rou te of immunization. Remarkably, oral administration of RHDV VLPs effic iently induced protecting antibodies to RHD at doses as low as 3 mu g. 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 a nd opens the door to the use of these capsids for the prevention of th e disease in wild animals. Therefore, a new. and potentially important application of recombinant VLPs in the induction of protective immuni ty by the oral route is foreseen.