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<p>The adaptable nature of <i>Escherichia coli</i>, shifting from benign to virulent forms, poses a major healthcare challenge due to rising multidrug resistance and hypervirulence. In this study, using an <i>in silico</i> reverse vaccinology approach, we designed a multiepitope mRNA vaccine candidate targeting the Shiga toxin 1 (<i>Stx1</i>) of <i>Shiga toxin-producing E. coli</i> (STEC). Two cytotoxic T-Lymphocyte (CTL), three Helper T-Lymphocyte (HTL), and two Linear B-Lymphocyte (LBL) epitopes were identified and selected through stringent computational filtering based on high antigenicity, non-allergenicity, and non-toxicity. These epitopes were joined using optimized linkers (EAAK, AAY, GPGPG, KK) and the adjuvant PefE to form a stable 184-residue multi-epitope construct. Physicochemical profiling predicted a molecular weight of 19969.45 Da, an antigenicity score of 0.9278 (VaxiJen v.2.0), a basic isoelectric point (pI) of 10.31, and structural stability. Structural analysis revealed 21.74% alpha-helical content. Molecular docking exhibited strong binding with human Toll-like receptor 2 TLR2 and TLR4, with weighted energy scores of − 1096.2 and − 1110.5&#xa0;kcal/mol, respectively, mediated by extensive hydrogen-bonding and salt-bridge networks. <i>In silico</i> immune simulation projected a strong clonal expansion of B-cells, active T-helper and cytotoxic T-cells, and higher cytokine production (IFN-γ, IL-10). Codon Adaptation Index (CAI) of 0.87 and a stable mRNA secondary structure were predicted with a minimum free energy (MFE) of − 204.10&#xa0;kcal/mol. While these computational findings provide immunogenic potential, they represent a predictive hypothesis. Subsequent in vitro synthesis and in vivo testing in animal models are essential to validate its safety, immunogenicity, and protective efficacy.</p>

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A novel multi-epitope mRNA vaccine against Escherichia coli using an in silico reverse vaccinology approach

  • 期刊论文

  • 发表日期：

    2026年7月30日

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  • Shakeela Parveen,
  • Javeria Abbasi,
  • Muhammad Hussain,
  • Muhammad Farhan Khan,
  • Muhammad Tayyab,
  • Amina Parveen,
  • Laiba Shafique

摘要

The adaptable nature of Escherichia coli, shifting from benign to virulent forms, poses a major healthcare challenge due to rising multidrug resistance and hypervirulence. In this study, using an in silico reverse vaccinology approach, we designed a multiepitope mRNA vaccine candidate targeting the Shiga toxin 1 (Stx1) of Shiga toxin-producing E. coli (STEC). Two cytotoxic T-Lymphocyte (CTL), three Helper T-Lymphocyte (HTL), and two Linear B-Lymphocyte (LBL) epitopes were identified and selected through stringent computational filtering based on high antigenicity, non-allergenicity, and non-toxicity. These epitopes were joined using optimized linkers (EAAK, AAY, GPGPG, KK) and the adjuvant PefE to form a stable 184-residue multi-epitope construct. Physicochemical profiling predicted a molecular weight of 19969.45 Da, an antigenicity score of 0.9278 (VaxiJen v.2.0), a basic isoelectric point (pI) of 10.31, and structural stability. Structural analysis revealed 21.74% alpha-helical content. Molecular docking exhibited strong binding with human Toll-like receptor 2 TLR2 and TLR4, with weighted energy scores of − 1096.2 and − 1110.5 kcal/mol, respectively, mediated by extensive hydrogen-bonding and salt-bridge networks. In silico immune simulation projected a strong clonal expansion of B-cells, active T-helper and cytotoxic T-cells, and higher cytokine production (IFN-γ, IL-10). Codon Adaptation Index (CAI) of 0.87 and a stable mRNA secondary structure were predicted with a minimum free energy (MFE) of − 204.10 kcal/mol. While these computational findings provide immunogenic potential, they represent a predictive hypothesis. Subsequent in vitro synthesis and in vivo testing in animal models are essential to validate its safety, immunogenicity, and protective efficacy.