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<p>The global burden of <i>Mycobacterium tuberculosis (M. tuberculosis)</i> and <i>Mycobacterium bovis (M. bovis)</i>, the rise of drug-resistant strains, necessitates an urgent need for developing more effective vaccines. This study employed an in-silico approach to design a multi-epitope vaccine targeting the PE_PGRS16 protein, a conserved virulence factor found across both species, including drug-resistant strains. PE_PGRS16 was chosen due to its extracellular localization, adhesion properties, and virulence characteristics, making it a promising vaccine target. Epitopes for B-cells, Cytotoxic T Lymphocytes, and Helper T Lymphocytes were selected based on antigenicity, non-toxicity, and immune response potential. The vaccine construct demonstrated favorable properties, including high antigenicity, solubility, and stability, with a low instability index (-31.31) and binding energy (-44.566) when docked to TLR4, suggesting its potential for immune activation. Griselimycin was incorporated as an adjuvant to enhance immunogenicity, as predicted by C-ImmSim simulations. Population coverage analysis for East Africa revealed high applicability, with 98.35% coverage for Class I epitopes, 100% coverage for Class II epitopes, and 100% combined coverage, with average hit values of 8.4, 12.26, and 20.66, respectively. These results suggest broad potential for global vaccine deployment. This study presents a novel multi-epitope vaccine targeting PE_PGRS16, with the potential to combat <i>Mycobacterium tuberculosis</i> and <i>Mycobacterium bovis</i> infections, including drug-resistant forms. Further experimental validation is necessary to confirm its efficacy and safety.</p>

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Design of a multi-epitope vaccine against drug-resistant mycobacterium tuberculosis and mycobacterium bovis using reverse vaccinology

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年7月26日

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  • Eva Akurut,
  • Yahaya Gavamukulya,
  • Julius Mulindwa,
  • Moses Isiagi,
  • Ronald Galiwango,
  • Mudarshiru Bbuye,
  • Ibra Lujumba,
  • Davis Kiberu,
  • Patricia Nabisubi,
  • Grace Kebirungi,
  • Andrew Kambugu,
  • Barbara Castelnuovo,
  • Gyaviira Nkurunungi,
  • Daudi Jjingo,
  • Brenda Oketch,
  • David Patrick Kateete,
  • Gerald Mboowa

摘要

The global burden of Mycobacterium tuberculosis (M. tuberculosis) and Mycobacterium bovis (M. bovis), the rise of drug-resistant strains, necessitates an urgent need for developing more effective vaccines. This study employed an in-silico approach to design a multi-epitope vaccine targeting the PE_PGRS16 protein, a conserved virulence factor found across both species, including drug-resistant strains. PE_PGRS16 was chosen due to its extracellular localization, adhesion properties, and virulence characteristics, making it a promising vaccine target. Epitopes for B-cells, Cytotoxic T Lymphocytes, and Helper T Lymphocytes were selected based on antigenicity, non-toxicity, and immune response potential. The vaccine construct demonstrated favorable properties, including high antigenicity, solubility, and stability, with a low instability index (-31.31) and binding energy (-44.566) when docked to TLR4, suggesting its potential for immune activation. Griselimycin was incorporated as an adjuvant to enhance immunogenicity, as predicted by C-ImmSim simulations. Population coverage analysis for East Africa revealed high applicability, with 98.35% coverage for Class I epitopes, 100% coverage for Class II epitopes, and 100% combined coverage, with average hit values of 8.4, 12.26, and 20.66, respectively. These results suggest broad potential for global vaccine deployment. This study presents a novel multi-epitope vaccine targeting PE_PGRS16, with the potential to combat Mycobacterium tuberculosis and Mycobacterium bovis infections, including drug-resistant forms. Further experimental validation is necessary to confirm its efficacy and safety.