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

Leishmaniasis is a chronic inflammatory zoonotic illness caused by protozoan flagellates belonging to the <i>Leishmania</i> genus. Current data suggest that over 1 billion people worldwide are susceptible to infection, primarily in tropical and subtropical countries, where up to 2 million new cases are reported annually. Therefore, the development of a vaccine is crucial to combating this disease. This study employed immunoinformatics approaches to design a multiepitope anti-<i>Leishmania</i> vaccine, GH₁₈-cp<i>Leish</i>, based on a cluster of six glycosyl hydrolases 18. We identified six helper T lymphocyte (HTL) epitopes and twenty-six cytotoxic T lymphocyte (CTL) epitopes with IC₅₀ values <50 nM, indicating high affinity. Additionally, we also identified 20 continuous and twenty-six discontinuous B-cell epitopes. Analysis for allergenicity and toxicity showed no potential to induce these phenomena. All data obtained from in silico tools suggest that physicochemical and biological studies indicate that the GH₁₈-cp<i>Leish</i> chimeric protein is a promising candidate for an anti-<i>Leishmania</i> vaccine. Docking analysis showed that the Pep₁-cp<i>Leish</i>::TLR₁, Pep₁-cp<i>Leish</i>::TLR₂, Pep₁-cp<i>Leish</i>::/TLR₃, and Pep₁-cp<i>Leish</i>::/TLR₄ complexes maintained a stable form. The best interaction cluster score was observed in the complex Pep₁-cp<i>Leish</i>::TLR₂ (center = -622.6 and lowest energy = -841.7 kcal.mol^-1) followed by the complexes Pep₁-cp<i>Leish</i>::TLR₄ (center = -590.3 and lowest energy = -590.3 kcal.mol^-1), Pep₁-cp<i>Leish</i>::TLR₃ (center = -589.1 and lowest energy = -657.0 kcal.mol^-1), and Pep₁-cp<i>Leish</i>::TLR₁ (center = -504.1 and lowest energy = -602.9 kcal.mol^-1), respectively. This study suggests that GH₁₈-cp<i>Leish</i> may be suitable for constructing second-generation anti-<i>Leishmania</i> and even third-generation vaccines, given that its gene sequence is optimized for this purpose.