Design of multi-epitope peptides containing HLA class-I and class-II-restricted epitopes derived from immunogenic Leishmania proteins, and evaluation of CD4+ and CD8+ T cell responses induced in cured cutaneous leishmaniasis subjects

摘要

The control of leishmaniasis, a neglected tropical disease of public health importance, caused by protozoan parasites of the genus Leishmania, mainly relies on chemotherapy, which is highly toxic. Currently, there is no vaccine against human leishmaniasis. Peptide-based vaccines consisting of T cell epitopes identified within proteins of interest by epitope predictive algorithms are a promising strategy for vaccine development. Here, we identified multi-epitope peptides composed of HLA-I and -II-restricted epitopes, using immunoinformatic tools, within Leishmania proteins previously described as potential vaccine candidates. We showed that multi-epitope peptides used as pools were able to activate IFN producing CD4+ as well as CD8+ T cells, both required for parasite elimination. In addition, granzyme B-producing CD4+ T cells, bifunctional CD4+ IFN+/TNF-+ and/or TNF-+/IL-2+ T cells as well as CD4+ and CD8+ central memory T cells, all involved in Leishmania infection control, were significantly increased in response to multi-epitope peptide stimulation. As far as we know, no study has described the detection of both CD4+ and CD8+ T cell populations in response to stimulation by both HLA-I and II-restricted peptides in humans. The immunogenic HLA-I and -II-restricted multi-epitope peptides identified in this study could constitute potential vaccine candidates against human leishmaniasis.