Assessment of protection induced by heterologous DNA-Live prime-boost encoding Leishmania MHC class I restricted epitopes against L. major challenge in BALB/c mice

CD8+-T-cells’ role in the control of L. major infection has recently attracted full attention in vaccine design. A new strategy has been proposed called T-cell-vaccine to present a number of immunogenic peptides from different proteins of a pathogen to the immune system and to induce specific T-CD8+ and T-CD4+ responses. Regarding the role of heterologous prime boost strategy to stimulate multi-functional CD8+-T-cells, the protective efficacy of Leishmania tarentolae as a live vector encoding four immunogenic H2Kd restricted peptides (PT) from 4 different L. major proteins was assessed as DNA-Live strategy against L. major high dose challenge in BALB/c mice. We hypothesized that CD8+-T-cell’s stimulation by polytope constructs diverts primary Th2 responses into Th1 resulting in disease control. Protective effect was evaluated by footpad swelling, parasite burden and immunological assays (IFN-γ/IL-5 ELISA, IFN-γ ICCS and CFSE) after L. majorEGFP infectious challenge of Balb/c mice. pcDNA-PT priming and live L. tarPT-EGFP boosting conferred a short term Th1 induced partial protection up to 3 weeks by CD8+-T-cell stimulation which was further potentiated by one extra DNA booster and CpG oligonucleotide complementation of live inoculum. Overally, it was concluded that the polytope structure (4 H2Kd restricted peptides), in DNA/Live regimen succeeded to confer partial protection by stimulation of CD8+-T-cells responses. It is highly supposed that substituting higher avidity peptides can further potentiate the construct by stimulating more potent CD8+-T-cells and longer effectiveness of the vaccine. This point is very important in vaccine design since CD8+-T-cells induce long memory responses of CD4+-T-cells.

کلیدواژه ها:

Leishmania major ، CD8+ T cells ، peptide vaccine