A RECOMBINANT VIRUS-LIKE PARTICLE SYSTEM DERIVED FROM PARVOVIRUS AS AN EFFICIENT ANTIGEN CARRIER TO ELICIT A POLARIZED TH1 IMMUNE-RESPONSE WITHOUT ADJUVANT

Hybrid virus-like particles (VLP) were prepared by self-assembly of th e modified porcine parvovirus (PPV) VP2 capsid protein carrying a CD8( +) or CD4(+) T cell epitope. Immunization of mice with a single dose o f these hybrid pseudo-particles, without adjuvant, induced strong cyto toxic T lymphocyte and T helper (Th) responses against the reporter ep itope. The Th response was characterized by a Th1 phenotype. We also a nalyzed in vitro the uptake mechanism of these parvovirus-like particl es and the processing requirements associated with presentation by MHC molecules. Although previously shown to be presented by MHC class I m olecules, these particles also enter very efficiently the MHC class II endocytic pathway, and behave as conventional exogenous antigens. Ind eed, the processing of chimeric PPV:VLP was performed in endosomal/lys osomal acidic vesicles and the presentation of the foreign epitope car ried by these particles was sensitive to brefeldin A and cycloheximide , showing that the foreign peptide was loaded on nascent MHC class II molecules. These results give some indication of how PPV:VLP can be pr esented by MHC class I and class II molecules, and underscore the wide potency of such VLP system to deliver foreign antigens for vaccine de sign.