A wide proteome analysis to engineer an efficient epitope based vaccine against Salmonella typhi: An immunoinformatic study.

BACKGROUND

Typhoid fever, a potentially fatal disease caused by Salmonella enterica serovar Typhi, requires effective vaccines. This study aimed to design a recombinant subunit vaccine using the most immunogenic proteins from the Salmonella Typhi proteome.

METHODS

Initially, the most antigenic proteins were selected to predict linear T-cell, B-cell, and IFN-γ epitopes. A recombinant construct incorporating these epitopes, peptide linkers, and a molecular adjuvant was designed. Comprehensive evaluation assessed physicochemical properties, solubility, secondary/tertiary structure, antigenicity, and immune stimulation potential. Molecular docking and dynamics simulations investigated binding to the TLR4/MD2 receptor complex.

RESULTS

Seven proteins from 4322 were chosen for epitope prediction, yielding a 655-amino acid construct. Physicochemical analysis showed 40.31 % hydrophobic amino acids, an aliphatic index of 53.66, GRAVY index of -0.712, and instability index of 22.34. Structural composition was 53.53 % alpha-helix, 8.85 % extended strand, and 40.61 % random coil. Immune simulations demonstrated significant enhancement of primary/secondary humoral and cellular immune responses. The vaccine construct effectively bound the TLR4/MD2 receptor via significant hydrogen bonding (affinity: -1019.1 kcal/mol). Molecular dynamics simulations confirmed the stability of this interaction over 200 ns, demonstrating that both the vaccine candidate and receptor remained structurally stable throughout the simulation period.

CONCLUSION

Typhoid vaccine candidate shows immunogenic properties, robust immune responses and stable TLR4/MD2 receptor binding.