Abstract
Many vaccine candidates against visceral leishmaniasis (VL) have been proposed; however, to date, none of them have been efficacious for the human or canine disease. On this basis, the design of leishmaniasis vaccines has been constantly changing, and the use of approaches to select specific epitopes seems to be crucial in this scenario. The ability to predict T cell-specific epitopes makes immunoinformatics an even more necessary approach, as in VL an efficient immune response against the parasite is triggered by T lymphocytes in response to Leishmania spp. immunogenic antigens. Moreover, the success of vaccines depends on the capacity to generate long-lasting memory and polyfunctional cells that are able to eliminate the parasite. In this sense, our study used a combination of different approaches to develop potential chimera candidate vaccines against VL. The first point was to identify the most immunogenic epitopes of Leishmania infantum proteins and construct chimeras composed of Major histocompatibility complex (MHC) class I and II epitopes. For this, we used immunoinformatics features. Following this, we validated these chimeras in a murine model in a thorough memory study and multifunctionality of T cells that contribute to a better elucidation of the immunological protective mechanisms of polyepitope vaccines (chimera A and B) using multicolor flow cytometry. Our results showed that in silico-designed chimeras can elicit polyfunctional T cells producing T helper (Th)1 cytokines, a strong immune response against Leishmania antigen, and the generation of central and effector memory T cells in the spleen cells of vaccinated animals that was able to reduce the parasite burden in this organ. These findings contribute two potential candidate vaccines against VL that can be used in further studies, and help in this complex field of vaccine development against this challenging parasite.
Highlights
During the last decades, the way in which the immune system works and the protective mechanisms related to vaccination for complex parasites has been extensively interpreted, and the central dogma of vaccination has been mounted [1]
The epitopes were repeated in tandem to enhance the immunogenicity, and GPGPG sequence was used as a linker
For predictions based on BLAST analyses, no hits were found for both chimera sequences and they did not contain experimentally proven Immunoglobulin E
Summary
The way in which the immune system works and the protective mechanisms related to vaccination for complex parasites has been extensively interpreted, and the central dogma of vaccination has been mounted [1]. Some studies support the idea that an antigen is capable of inducing long-lasting immunological memory and protective immunity against re-challenge with the same pathogen This concept has been successful in generating potent vaccines for many diseases, leishmaniasis caused by the protozoan parasite Leishmania remains a threatening exception. In light of this, seeking to expand the antigenic repertoire of vaccines, the authors of [3] constructed a multiepitope DNA vaccine that encoded four protein-fused peptides, lipophosphoglycan (LPG)-3, Leishmania major stress inducible protein (LmSTI)-1, cysteine peptidase B (CPB), and cysteine peptidase C (CPC). They evaluated the cytotoxic activity of lymphocytes and IFN-γ production in transgenic mouse
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