We propose to develop genetically engineered candidate vaccine for Bovine Leukemia Virus (BLV) that can serve as a model system to develop strategies to prevent diseases induced by human T-cell lymphotropic virus (HTLV). Known B and T cell epitopes as well as overlapping fragments of BLV external glycoprotein gp5l will be presented in a 68 nm particulate structure formed by VP7 and VP3 proteins of bluetongue virus (BTV). The VP7 protein which is layered onto the scaffold of VP3 can accommodate, in- frame, an end addition of at least 50 amino acids residues. The inserted foreign epitope is not only exposed in the surface, recognized by the host immune system, but has no negative effect on the formation of the core- like particles (CLPs). In addition, a number of regions on the VP7, the surface protein of CLPs have now been identified (due to the availability of the three-dimensional crystallographic structure of VP7), that can be manipulated for insertion of additional BLV epitopes. CLPs of bluetongue virus are synthesized, at high level, by the baculovirus expression system. The chimeric particles will be tested for their protective efficacy against BLV infection and/or against BLV disease in sheep and rabbits. If positive, the approach based on HCA analysis will be extended to HTLV-1 gp46 in rabbits and to STLV-1 gp46 in primates.
