Evaluation of protection induced by in vitro maturated BMDCs presenting CD8+ T cell stimulating peptides after a heterologous vaccination regimen in BALB/c model against Leishmania major.

Leishmaniasis is a complex vector-borne disease mediated by Leishmania parasite and a strong and long-lasting CD4+ Th1 and CD8+-T cell immunity is required to control the infection. Thus far multivalent subunit vaccines have met this requirement more promisingly. However several full protein sequences cannot be easily arranged in one construct. Instead, new emerging immune-informatics based epitope formulations surpass this restriction. Herein, we aimed to examine the protective potential of a dendritic cell based vaccine presenting epitopes to CD8+ and CD4+-T cells in combination with DNA vaccine encoding the same epitopes against murine cutaneous leishmaniasis. Immature DCs were loaded with epitopes (selected from parasite proteome) in vitro with or without CpG oligonucleotides and were used to immunize BALB/c mice. Peptide coding DNA was used to boost the system and immunological responses were evaluated after Leishmania (L.) major infectious challenge. The pre-challenge response to included epitopes was Th1 polarized which potentially lowered the infection at early time points post-challenge but not at later weeks. Collectively, DC prime-DNA boost was found to be a promising approach for Th1 polarization however the constituent epitopes undoubtedly make a significant contribution in the protection outcome of the vaccine. [Display omitted] • Leishmaniasis is a complex vector-borne disease without effective vaccine. • Multivalent subunit vaccines formulated as recombinant proteins or DNA constructs have generated more promising results. • Multi-epitope peptide-based vaccines have now come into focus to make multivalent vaccines more achievable. • DC prime-DNA boost strategy could be a promising formulation for robust Th1 polarization against immunogenic epitopes. • Constituent epitopes of a multi-epitope peptide-based vaccine play a significant role in vaccine efficacy. [ABSTRACT FROM AUTHOR]