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Background <p>Shigellosis and salmonellosis are prominent food-borne illnesses associated with high mortality rates and morbidity, for which, as of now, no licensed vaccine is available. Multiple epitope vaccines offer promising prospects as alternatives to conventional vaccines by combining extremely immunogenic as well as conserved epitopes to overcome weaknesses related to weak antigens as well as serotype specificity.</p> Methods <p>For the first time, this study focused on developing a new protective multiepitope vaccine for dual protection against <i>Salmonella</i> and <i>Shigella</i> by integrating six conserved virulence factors: SpvB, SipD, RcK, SigA, IpaD, and FimA.</p> Results <p>When immunoinformatics tools were applied, highly conserved B- and T-cell epitopes with broad HLA allele coverage and high antigenicity were predicted, while allergenicity and toxicity assessments were used to assess safety. The selected epitopes were conjugated with suitable spacers to maintain structural integrity and increase immune processing. The conserved domain of the <i>Salmonella</i> flagellin protein (FliC) was used as both the scaffold and the TLR5 agonist adjuvant. Secondary and tertiary FliC-based multiepitope construct (FMEC) structures were predicted, refined, and validated; these structures exhibited desirable physicochemical properties, such as stability, hydrophilicity, and thermal resilience, with a molecular weight of 33&#xa0;kDa, which is ideal for vaccine construction. In addition, ProSA and Ramachandran plot validation confirmed the reliability of the FMEC model. Immune simulation demonstrated powerful cellular and humoral immunity, whereas molecular docking and normal mode analysis confirmed the stable interaction of FMEC with the TLR4/5 or MHCI/MHCII receptors.</p> Conclusion <p>Although FMEC shows promise as a safe, nontoxic, nonallergen, and widely immunogenic multiepitope vaccine candidate to combat <i>Salmonella</i> and <i>Shigella</i>, further experimental validation needs to be carried out to ascertain its in vivo protective efficacy.</p> Trial registration <p>Not applicable.</p>

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Innovative multi-epitope vaccine engineering for dual protection against Salmonella and Shigella leveraging FliC flagellin protein adjuvant properties: an immunoinformatics-based approach

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月16日

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  • Elnaz Afshari,
  • Neda Soleimani

摘要

Background

Shigellosis and salmonellosis are prominent food-borne illnesses associated with high mortality rates and morbidity, for which, as of now, no licensed vaccine is available. Multiple epitope vaccines offer promising prospects as alternatives to conventional vaccines by combining extremely immunogenic as well as conserved epitopes to overcome weaknesses related to weak antigens as well as serotype specificity.

Methods

For the first time, this study focused on developing a new protective multiepitope vaccine for dual protection against Salmonella and Shigella by integrating six conserved virulence factors: SpvB, SipD, RcK, SigA, IpaD, and FimA.

Results

When immunoinformatics tools were applied, highly conserved B- and T-cell epitopes with broad HLA allele coverage and high antigenicity were predicted, while allergenicity and toxicity assessments were used to assess safety. The selected epitopes were conjugated with suitable spacers to maintain structural integrity and increase immune processing. The conserved domain of the Salmonella flagellin protein (FliC) was used as both the scaffold and the TLR5 agonist adjuvant. Secondary and tertiary FliC-based multiepitope construct (FMEC) structures were predicted, refined, and validated; these structures exhibited desirable physicochemical properties, such as stability, hydrophilicity, and thermal resilience, with a molecular weight of 33 kDa, which is ideal for vaccine construction. In addition, ProSA and Ramachandran plot validation confirmed the reliability of the FMEC model. Immune simulation demonstrated powerful cellular and humoral immunity, whereas molecular docking and normal mode analysis confirmed the stable interaction of FMEC with the TLR4/5 or MHCI/MHCII receptors.

Conclusion

Although FMEC shows promise as a safe, nontoxic, nonallergen, and widely immunogenic multiepitope vaccine candidate to combat Salmonella and Shigella, further experimental validation needs to be carried out to ascertain its in vivo protective efficacy.

Trial registration

Not applicable.