Recombinant VP2 paraviral pseudo-particles encoding CTL or T-helper cell epitopes

摘要

Attempts to generate modified viral pseudo-particles that are capable of stably incorporating heterologous antigenic determinants has encountered a number of difficulties including inhibition of pseudo-particle formation following epitope insertion and failure of the epitope to retain its native configuration. The present invention is directed toward recombinant viral pseudo-particles of the family Parvoviridae that stably encode heterologous epitopes. Hybrid virus-like particles (VLP) were prepared by self-assembly of a modified porcine parvovirus (PPV) VP2 capsid protein carrying a CD8+ or CD4+ T cell epitope in the amino terminus. Immunization of mice with hybrid pseudo-particles carrying a lymphocytic choriomeningitis virus (LCMV) nucleoprotein CTL epitope, without adjuvant, induced strong cytotoxic T lymphocyte (CTL) responses against both peptide-coated- or virus-infected-target cells. Immunization of mice with hybrid pseudo-particles carrying a hepatitis B virus (HBV) T helper cell epitope, without adjuvant, induced strong T helper lymphocyte responses against the reporter epitope. These recombinant viral pseudo-particles are easily produced by the baculovirus expression system and, therefore, represent a promising and safe strategy to induce strong CTL and T-helper cell responses for the elimination of virus-infected cells.