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Background <p><i>Mycobacterium tuberculosis</i> infects one-fourth of the global population, and current challenges such as latent infections, multidrug-resistant strains, and the limited efficacy of the BCG vaccine emphasize the urgent need for next-generation vaccines. This study aimed to introduce novel vaccine candidates, immunoreactive epitopes, and a novel multi-epitope vaccine (MEV).</p> Methods <p>New immunogenic targets were identified based on different characteristics, including subcellular localization, antigenicity, non-similarity to the host proteome, sequence conservation, prevalence, and B-cell and T-cell epitopes. In the next step, IFN-γ releasing immunoreactive epitopes with a high similarity to TCR-interacting epitopes were identified. The MEV was generated using shortlisted epitopes and the C-terminal fragment of <i>Clostridium perfringens</i> enterotoxin (CPE). Finally, the interactions of MEV epitopes with human MHC I and MHC II alleles were investigated.</p> Results <p>In the first step, a total of seven proteins with desired immunogenic properties were introduced as novel immunogenic targets. Comparison of surface-exposed proteins to 4718 immunoreactive linear B-cell epitopes of <i>M. tuberculosis</i> resulted in identification of 719 non-redundant immunoreactive epitopes. Finally, seven immunoreactive, IFN-γ releasing epitopes with significant homology to TCR binding epitopes were employed to design a MEV. This MEV showed desirable structural and immunogenic properties. Moreover, it revealed promising interactions with human MHC I and MHC II alleles in molecular docking.</p> Conclusion <p>This study suggests PE/PPE proteins and TCR-recognized immunoreactive peptides as promising vaccine components against tuberculosis. In addition, the designed MEV with the C-terminal fragment of CPE may represent a potential candidate for future development as a mucosal vaccine against <i>M. tuberculosis</i>.</p>

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Design of a multi-epitope vaccine against Mycobacterium tuberculosis using reverse vaccinology and immunoreactive peptides

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月8日

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  • Narjes Noori Goodarzi,
  • Sepideh Fereshteh,
  • Behzad Shahbazi,
  • Niloofar Rezaie,
  • Mahshid Khazani Asforooshani,
  • Farzad Badmasti

摘要

Background

Mycobacterium tuberculosis infects one-fourth of the global population, and current challenges such as latent infections, multidrug-resistant strains, and the limited efficacy of the BCG vaccine emphasize the urgent need for next-generation vaccines. This study aimed to introduce novel vaccine candidates, immunoreactive epitopes, and a novel multi-epitope vaccine (MEV).

Methods

New immunogenic targets were identified based on different characteristics, including subcellular localization, antigenicity, non-similarity to the host proteome, sequence conservation, prevalence, and B-cell and T-cell epitopes. In the next step, IFN-γ releasing immunoreactive epitopes with a high similarity to TCR-interacting epitopes were identified. The MEV was generated using shortlisted epitopes and the C-terminal fragment of Clostridium perfringens enterotoxin (CPE). Finally, the interactions of MEV epitopes with human MHC I and MHC II alleles were investigated.

Results

In the first step, a total of seven proteins with desired immunogenic properties were introduced as novel immunogenic targets. Comparison of surface-exposed proteins to 4718 immunoreactive linear B-cell epitopes of M. tuberculosis resulted in identification of 719 non-redundant immunoreactive epitopes. Finally, seven immunoreactive, IFN-γ releasing epitopes with significant homology to TCR binding epitopes were employed to design a MEV. This MEV showed desirable structural and immunogenic properties. Moreover, it revealed promising interactions with human MHC I and MHC II alleles in molecular docking.

Conclusion

This study suggests PE/PPE proteins and TCR-recognized immunoreactive peptides as promising vaccine components against tuberculosis. In addition, the designed MEV with the C-terminal fragment of CPE may represent a potential candidate for future development as a mucosal vaccine against M. tuberculosis.