An Integrated Comparative Genomics, Subtractive Proteomics and Immunoinformatics Framework for the Rational Design of a Pan-SalmonellaMulti-Epitope Vaccine

Abstract

AbstractSalmonellainfections are a global public health issue due to the high cost of illness surveillance, prevention, and treatment. In this study, we explored the core proteome inSalmonellato design a multi-epitope vaccine through Subtractive Proteomics and immunoinformatics approaches. A total of 2395 core proteins presents in 30 different strains ofSalmonella(reference strain-NZ CP014051) were curated. Utilizing the subtractive proteomics approach on theSalmonellacore proteome, Curlin major subunit A (CsgA) was selected as the vaccine candidate.csgAis a conserved gene that is related with biofilm formation. Immunodominant B and T cell epitopes from CsgA were predicted using numerous immunoinformatics tools. T lymphocyte epitopes had adequate population coverage and their corresponding MHC alleles showed significant binding scores after peptide-protein based molecular docking. Afterward, a multiepitope vaccine was constructed with peptide linkers and Human Beta Defensin-2 (as an adjuvant). The vaccine was found to be highly antigenic, non-toxic, non-allergic, and had physicochemical properties. Additionally, Molecular Dynamics Simulation and Immune Simulation demonstrated that the vaccine can bind with Toll Like Receptor 4 and elicit robust immune response. Usingin vitro,in vivo, and clinical trials, our results would yield a Pan-Salmonellavaccine that will provide protection against variousSalmonellaspecies.