Immunoinformatics-based design and in silico evaluation of a PstS-derived multi-epitope vaccine candidate against Salmonella typhimurium

Abstract

Abstract Salmonella typhimurium is a major foodborne pathogen with increasing multidrug resistance and limited vaccine options. This study aimed to design a multi-epitope vaccine targeting the PstS protein using an immunoinformatics approach. B-cell and T-cell epitopes were predicted, screened, and assembled into a chimeric construct with an adjuvant and linkers. The vaccine was evaluated for physicochemical properties, structural stability, and population coverage. Molecular docking with TLR4 and 100 ns molecular dynamics simulations were performed, followed by in silico immune simulation and codon optimization. The designed construct showed high antigenicity, stability, and hydrophilicity with broad population coverage (> 97%). Structural validation confirmed a stable fold. Docking demonstrated strong binding to TLR4, which remained stable during molecular dynamics simulations. Immune simulation predicted robust antibody and T-cell responses with a dominant Th1-type profile. The proposed multi-epitope vaccine shows promising immunological and structural properties, supporting its potential against S. typhimurium , pending experimental validation.