A recombinant virus-like particle system derived from parvovirus as an efficient antigen carrier to elicit a polarized Th1 immune response without adjuvant
✍ Scribed by Richard Lo-Man; Paloma Rueda; Christine Sedlik; Edith Deriaud; Ignacio Casal; Claude Leclerc
- Publisher
- John Wiley and Sons
- Year
- 1998
- Tongue
- English
- Weight
- 159 KB
- Volume
- 28
- Category
- Article
- ISSN
- 0014-2980
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✦ Synopsis
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.