<p>Shiga toxin-producing <i>Escherichia coli</i> (STEC) is a major public health concern due to its association with severe illnesses such as hemorrhagic colitis and hemolytic uremic syndrome. Vaccination offers a promising strategy to mitigate STEC carriage in cattle, thereby reducing human exposure. This study utilized a computational framework to design multi-epitope vaccine candidates targeting Shiga toxins. The key epitopes from Stx1A, Stx1cB, Stx2A, Stx2B, and Stx2f subunits were identified and prioritized based on immunogenicity and allergenicity profiles. Eight vaccine constructs were designed, incorporating diverse epitopes connected via linkers and adjuvants. Physicochemical analyses confirmed the constructs stability, solubility, and antigenicity. Secondary and tertiary structure predictions demonstrated accurate folding and structural reliability. Molecular docking revealed strong interactions with Toll-like receptor 4 (TLR4), with vaccine candidates VC-3 and VC-5 showing the highest binding affinities. Molecular dynamics simulations confirmed the stability and compactness of these complexes and revealed VC5 as the best stable complex. Codon optimization and in silico cloning ensured efficient expression in <i>Escherichia coli.</i> These findings highlight the potential of the proposed vaccine constructs to elicit robust immune responses and provide broad-spectrum protection against STEC infections. Experimental validation and preclinical studies are warranted to advance these candidates toward clinical applications.</p>

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Next-generation T cell-based in-silico multi-epitope vaccines: bridging cross-protection across diverse Shiga toxin variants

  • T. Dhanushkumar,
  • J. Deepika,
  • C. S. Aishwarya,
  • B. G. Sunila,
  • C. George Priya Doss,
  • Karthick Vasudevan

摘要

Shiga toxin-producing Escherichia coli (STEC) is a major public health concern due to its association with severe illnesses such as hemorrhagic colitis and hemolytic uremic syndrome. Vaccination offers a promising strategy to mitigate STEC carriage in cattle, thereby reducing human exposure. This study utilized a computational framework to design multi-epitope vaccine candidates targeting Shiga toxins. The key epitopes from Stx1A, Stx1cB, Stx2A, Stx2B, and Stx2f subunits were identified and prioritized based on immunogenicity and allergenicity profiles. Eight vaccine constructs were designed, incorporating diverse epitopes connected via linkers and adjuvants. Physicochemical analyses confirmed the constructs stability, solubility, and antigenicity. Secondary and tertiary structure predictions demonstrated accurate folding and structural reliability. Molecular docking revealed strong interactions with Toll-like receptor 4 (TLR4), with vaccine candidates VC-3 and VC-5 showing the highest binding affinities. Molecular dynamics simulations confirmed the stability and compactness of these complexes and revealed VC5 as the best stable complex. Codon optimization and in silico cloning ensured efficient expression in Escherichia coli. These findings highlight the potential of the proposed vaccine constructs to elicit robust immune responses and provide broad-spectrum protection against STEC infections. Experimental validation and preclinical studies are warranted to advance these candidates toward clinical applications.