AUTHOR=Flórez Magda Melissa , Rodríguez Rocío , Cabrera José Antonio , Robledo Sara M. , Delgado Gabriela 

TITLE=Leishmania spp Epitopes in Humans Naturally Resistant to the Disease: Working Toward a Synthetic Vaccine

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=Volume 11 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2021.631019

DOI=10.3389/fcimb.2021.631019

ISSN=2235-2988

ABSTRACT=Vaccines are one of the most effective strategies to fight infectious diseases. Reverse vaccinology strategies provide tools to perform in silico screening and a rational selection of potential candidates on a large scale before reaching in vitro and in vivo evaluations. Leishmania infection in humans produces clinical symptoms in less than 20%, reflecting that about 80% of the population is naturally resistant to the disease, and therefore their immune response control parasite replication. By the identification of epitopes directly in humans, especially in those Resistant to the disease, the probabilities of designing an effective vaccine are higher. The aim of this work was the identification of Leishmania epitopes in resistant humans. To achieve that, 11 peptide sequences (from Leishmania antigenic proteins) were selected using epitope prediction tools, and then, PBMCs were isolated from human volunteers with previous divided into four clinical groups: Susceptible, Resistant, Exposed and NO Exposed to the parasite. The induction of inflammatory cytokines and lymphoproliferation was assessed using monocyte-derived Dendritic Cells as Antigen Presenting cells were evaluated after exposing volunteer cells to each peptide. As result, we obtained that STI41 and STI46 peptides induced IL-8 and IL-12 in moDCs, plus the induction of lymphoproliferation and low levels of IL-10 in lymphocytes differentially in Resistant volunteers, similar behavior than the observed in those individuals to L. panamensis lysate antigens.  We conclude that, In silico analysis, allowed the identification of Leishmania natural epitopes in humans, and also STI41 and STI46 peptides could be epitopes that lead to a cellular immune response directed to parasite control.