Immuno-Informatics for the Rational Design of Multi-Epitope Vaccine Against Leishmania donovani

Parasite Immunol. 2025 Sep;47(9):e70030. doi: 10.1111/pim.70030.

Abstract

Trypanothione reductase (TryR) is a unique and key redox protein of Leishmania donovani, the causative agent of visceral Leishmaniasis. In this work, we have developed a promising multiepitope vaccine using TryR. Multiple epitopes from TryR were identified using different bioinformatics tools to stimulate both humoral and cellular immune responses. An adjuvant was also included to enhance the antigen presentation and immune activation. Using bioinformatics tools, immunodominant T-cell and B-cell epitopes of TryR were predicted, and based on the findings, a chimeric multi-epitope vaccine construct was designed. The structural stability of the final construct was validated using different bioinformatics tools. Furthermore, a docking study was conducted with the human TLR4 receptor to assess the affinity of the multi-epitope construct. The Ramachandran plot analysis, Z score, and ERRAT support the stability of the multi-epitope vaccine candidate. Furthermore, in silico analysis showed that the multi-epitope vaccine candidate has high affinity with the human TLR4 receptor and has broad efficacy based on the population coverage. Immune stimulation confirmed the pro-inflammatory response with T- and B-cell activation.

Keywords: immunology modelling; leishmaniasis; multi‐epitope vaccine.

MeSH terms

  • Animals
  • Computational Biology
  • Epitopes, B-Lymphocyte* / genetics
  • Epitopes, B-Lymphocyte* / immunology
  • Epitopes, T-Lymphocyte* / genetics
  • Epitopes, T-Lymphocyte* / immunology
  • Humans
  • Leishmania donovani* / enzymology
  • Leishmania donovani* / genetics
  • Leishmania donovani* / immunology
  • Leishmaniasis Vaccines* / genetics
  • Leishmaniasis Vaccines* / immunology
  • Leishmaniasis, Visceral* / immunology
  • Leishmaniasis, Visceral* / prevention & control
  • Molecular Docking Simulation
  • NADH, NADPH Oxidoreductases* / chemistry
  • NADH, NADPH Oxidoreductases* / genetics
  • NADH, NADPH Oxidoreductases* / immunology
  • Toll-Like Receptor 4 / immunology
  • Toll-Like Receptor 4 / metabolism

Substances

  • Epitopes, B-Lymphocyte
  • Epitopes, T-Lymphocyte
  • Leishmaniasis Vaccines
  • NADH, NADPH Oxidoreductases
  • trypanothione reductase
  • Toll-Like Receptor 4