Use of parvovirus-like particles for vaccination and induction of multiple immune responses.

Abstract

Expression of the VP2 gene of autonomous parvoviruses in insect cells with the use of the baculovirus system has led to the production of virus-like particles (VLPs) formed by the self-assembly of VP2. These VLPs are expressed at high levels and can easily be purified by salt fractionation. They are highly immunogenic in the corresponding host, being fully protective at doses as low as 1-2 microg of purified material per animal. No special adjuvants are required. An interesting property of these particles is their usefulness as a diagnostic reagent for ELISA kits, which have successfully replaced conventional methods for parvovirus diagnostics based on haemagglutination. Another application of the hybrid recombinant parvovirus-like particles of pig parvovirus (PPV) and canine parvovirus (CPV) is its use as an antigen delivery system. PPV:VLPs containing a CD8(+) epitope from the lymphocytic choriomeningitis virus (LCMV) nucleoprotein are able to evoke a potent cytolytic T-lymphocyte response and to protect mice against a lethal infection with LCMV. Also, PPV:VLPs containing the C3:T epitope from poliovirus elicited a T helper response in mice. These T-cell epitopes were inserted into the N-terminus of the VP2 protein. Unfortunately, the N-terminus is not adequate for antibody responses because it is inside the particle. Recent findings have shown that fine tailoring of the point of insertion around the tip of loop 2 of the surface of CPV allowed the elicitation of a potent antibody response. Thus mice immunized with chimaeric C3:B CPV:VLPs were able to elicit a strong neutralizing antibody response (>3 log10 units) against poliovirus. We now have the possibility of using these particles to elicit different immune responses against single or multiple pathogens in a simple and economic way.