Molecular and Immunological\nProperties of a Chimeric\nGlycosyl Hydrolase 18 Based on Immunoinformatics Approaches: A Design\nof a New Anti-<i>Leishmania</i> Vaccine

Leishmaniasis is\na chronic inflammatory zoonotic illness\ncaused\nby protozoan flagellates belonging to the <i>Leishmania</i> genus. Current data suggest that over 1 billion people worldwide\nare susceptible to infection, primarily in tropical and subtropical\ncountries, where up to 2 million new cases are reported annually.\nTherefore, the development of a vaccine is crucial to combating this\ndisease. This study employed immunoinformatics approaches to design\na multiepitope anti-<i>Leishmania</i> vaccine, GH<sub>18</sub>-cp<i>Leish</i>, based on a cluster of six glycosyl hydrolases\n18. We identified six helper T lymphocyte (HTL) epitopes and twenty-six\ncytotoxic T lymphocyte (CTL) epitopes with IC<sub>50</sub> values\n<50 nM, indicating high affinity. Additionally, we also identified\n20 continuous and twenty-six discontinuous B-cell epitopes. Analysis\nfor allergenicity and toxicity showed no potential to induce these\nphenomena. All data obtained from in silico tools suggest that physicochemical\nand biological studies indicate that the GH<sub>18</sub>-cp<i>Leish</i> chimeric protein is a promising candidate for an anti-<i>Leishmania</i> vaccine. Docking analysis showed that the Pep<sub>1</sub>-cp<i>Leish</i>::TLR<sub>1</sub>, Pep<sub>1</sub>-cp<i>Leish</i>::TLR<sub>2</sub>, Pep<sub>1</sub>-cp<i>Leish</i>::/TLR<sub>3</sub>, and Pep<sub>1</sub>-cp<i>Leish</i>::/TLR<sub>4</sub> complexes maintained a stable form. The best interaction\ncluster score was observed in the complex Pep<sub>1</sub>-cp<i>Leish</i>::TLR<sub>2</sub> (center = −622.6 and lowest\nenergy = −841.7 kcal.mol<sup>–1</sup>) followed by the\ncomplexes Pep<sub>1</sub>-cp<i>Leish</i>::TLR<sub>4</sub> (center = −590.3 and lowest energy = −590.3 kcal.mol<sup>–1</sup>), Pep<sub>1</sub>-cp<i>Leish</i>::TLR<sub>3</sub> (center = −589.1 and lowest energy = −657.0\nkcal.mol<sup>–1</sup>), and Pep<sub>1</sub>-cp<i>Leish</i>::TLR<sub>1</sub> (center = −504.1 and lowest energy = −602.9\nkcal.mol<sup>–1</sup>), respectively. This study suggests that\nGH<sub>18</sub>-cp<i>Leish</i> may be suitable for constructing\nsecond-generation anti-<i>Leishmania</i> and even third-generation\nvaccines, given that its gene sequence is optimized for this purpose.