Immunoinformatics design of a novel multiepitope vaccine candidate against non-typhoidal salmonellosis caused by Salmonella Kentucky using outer membrane proteins A, C, and F

The global public health risk posed by Salmonella Kentucky (S. Kentucky) is rising, particularly due to the dissemination of antimicrobial resistance genes in human and animal populations. This serovar, widespread in Africa, has emerged as a notable cause of non-typhoidal gastroenteritis in humans. In this study, we used a bioinformatics approach to develop a peptide-based vaccine targeting epitopes from the outer membrane proteins A, C, and F of S. Kentucky. Additionally, we employed flagellin protein (fliC) from Salmonella Typhimurium (S. Typhimurium) as an adjuvant to enhance the vaccine's effectiveness. Through this approach, we identified 14 CD8+ and 7 CD4+ T-cell epitopes, which are predicted to be restricted by various MHC class I and MHC class II alleles. The predicted epitopes are expected to achieve a population coverage of 94.91% when used in vaccine formulations. Furthermore, we identified seven highly immunogenic linear B-cell epitopes and three conformational B-cell epitopes. These T-cell and B-cell epitopes were then linked using appropriate linkers to create a multi-epitope vaccine (MEV). To boost the immunogenicity of the peptide construct, fliC from S. Typhimurium was included at the N-terminal. The resulting MEV construct demonstrated high structural quality and favorable physicochemical properties. Molecular docking studies with Toll-like receptors 1, 2, 4, and 5, followed by molecular dynamic simulations, suggested that the vaccine-receptor complexes are energetically feasible, stable, and robust. Immune simulation results showed that the MEV elicited significant responses, including IgG, IgM, CD8+ T-cells, CD4+ T-cells, and various cytokines (IFN-γ, TGF-β, IL-2, IL-10, and IL-12), along with a noticeable reduction in antigen levels. Despite these promising in-silico findings, further validation through preclinical and clinical trials is required to confirm the vaccine's efficacy and safety.