Engineering parvovirus-like particles for the induction of B-cell, CD4(+) and CTL responses

An antigen delivery system based on hybrid recombinant parvovirus-like part icles (VLPs) formed by the self-assembly of the capsid VP2 protein of porci ne (PPV) or canine parvovirus (CPV) expressed in insect cells with the bacu lovirus system has been developed. PPV:VLPs containing a CD8(+) epitope fro m the LCMV nucleoprotein evoked a potent CTL response and were able to prot ect mice against a lethal infection with the virus. Also, PPV:VLPs containi ng the C3:T epitope from poliovirus elicited a CD4(+) response in mice. The se T-cell epitopes were located in the N-terminus of the VP2 protein. Unfor tunately, the N-terminus is not adequate for antibody responses because it is inside the particle. Previous attempts to modify the surface-exposed reg ions of the capsid were unsuccessful. Deletions in the four loops of the su rface resulted in the complete disruption of the particles except those in loop 2. However, preliminary insertions of the C3:B epitope of poliovirus i n VP2 residue 225 of the loop 2 were not able to elicit antibody responses. To optimise the insertion site, the epitope was inserted consecutively in positions 226, 227 and 228, which seem to be more accessible on the capsid. Mice immunised with these chimeric C3:B CPV:VLPs were able to elicit a str ong neutralising antibody response (> 3 log(10) units) against poliovirus. The possibility of combining different types of epitopes in different posit ions of a single particle to stimulate different branches of the immune sys tem paves the way to the production of more potent vaccines in a simple and cheap way. (C) 1999 Elsevier Science Ltd. All rights reserved.