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 the modified porcine parvovirus (PPV) VP2 capsid protein carrying a CD8+ or CD4+ T cell epitope. Immunization of mice with a single dose of these hybrid pseudo-particles, without adjuvant, induced strong cytotoxic T lymphocyte and T helper (Th) responses against the reporter epitope. The Th response was characterized by a Th1 phenotype. We also analyzed in vitro the uptake mechanism of these parvovirus-like particles and the processing requirements associated with presentation by MHC molecules. Although previously shown to be presented by MHC class I molecules, these particles also enter very efficiently the MHC class II endocytic pathway, and behave as conventional exogenous antigens. Indeed, the processing of chimeric PPV:VLP was performed in endosomal/lysosomal acidic vesicles and the presentation of the foreign epitope carried 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 presented by MHC class I and class II molecules, and underscore the wide potency of such VLP system to deliver foreign antigens for vaccine design.
Lo-Man
R
R
Unité de Biologie des Régulations Immunitaires, Institut Pasteur, Paris, France. rloman@pasteur.fr
Rueda
P
P
Sedlik
C
C
Deriaud
E
E
Casal
I
I
Leclerc
C
C
D000276:Adjuvants, Immunologic; D000818:Animals; D000956:Antigens, Viral / Q000008:administration & dosage / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D017992:Parvovirus / Q000235:genetics / Q000276:immunology*; D011995:Recombination, Genetic; D018417:Th1 Cells / Q000276:immunology*; D014771:Virion / Q000276:immunology*
D000276:Adjuvants, Immunologic; D000956:Antigens, Viral