Computational design of a multi-epitope vaccine against Helicobacter pylori targeting CagA, FliD, urease, and OipA with cholera toxin B subunit (CTB) adjuvant

Helicobacter pylori, a Gram-negative, microaerophilic bacterium with a characteristic spiral morphology, inhabits the stomachs of approximately half of the world’s population. This study aimed to design a multi-epitope vaccine against H. pylori using immunoinformatics approaches, targeting key virulence factors including FliD, CagA, OipA, and urease. A multi-epitope vaccine was constructed by linking nine immunodominant epitopes from FliD, urease, CagA, and OipA and the cholera toxin B subunit (CTB) adjuvant. The resulting construct was rigorously evaluated through computational analyses to assess its physicochemical properties, structural stability, molecular docking with TLR2/TLR4, molecular dynamics (MD) simulations, and immune response profiling. Nine immunodominant epitopes from FliD, urease, CagA, and OipA, selected based on overlapping predictions of B and T cell epitopes, were linked with CTB. Structural modeling and validation predicted a stable tertiary structure, while molecular docking revealed strong interactions with TLR2 and TLR4, key receptors of innate immunity. Molecular dynamics simulations over 100 nanoseconds (ns) demonstrated structural stability for both complexes, with the vaccine-TLR4 complex showing higher stability than TLR2. Immune simulations predicted robust humoral and cellular responses, indicating sustained immunity. This study successfully designed a novel multi-epitope vaccine candidate against Helicobacter pylori using a comprehensive immunoinformatics approach. These comprehensive in silico analyses suggest that the proposed vaccine is a highly promising candidate for combating Helicobacter pylori infections; however, further in vitro and in vivo studies are essential to validate its efficacy and safety.