An integrated comparative genomics, subtractive proteomics and immunoinformatics framework for the rational design of a Pan-Salmonella multi-epitope vaccine

• Published in: PloS one Vol. 19; no. 7; p. e0292413
• Main Authors: Bhattacharjee, Arittra, Hosen, Md Rakib, Lamisa, Anika Bushra, Ahammad, Ishtiaque, Chowdhury, Zeshan Mahmud, Jamal, Tabassum Binte, Sohag, Md Mehadi Hasan, Hossain, Mohammad Uzzal, Das, Keshob Chandra, Keya, Chaman Ara, Salimullah, Md
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 03.07.2024
• Subjects: Amino acids; Animals; Antibiotics; Antigenic determinants; Bacterial Proteins - chemistry; Bacterial Proteins - genetics; Bacterial Proteins - immunology; Biocompatibility; Biofilms; Bioinformatics; Biology and Life Sciences; Clinical trials; Comparative analysis; Computational Biology - methods; Contamination; Defensins; Epitopes; Epitopes, B-Lymphocyte - immunology; Epitopes, T-Lymphocyte - immunology; Fatalities; Fever; Fourier transforms; Gastroenteritis; Genomes; Genomics; Genomics - methods; Health aspects; Humans; Immune response; Immune system; Immunoinformatics; Infection; Infections; Localization; Lymphocytes; Lymphocytes T; Major histocompatibility complex; Medical research; Medicine and Health Sciences; Medicine, Experimental; Metabolism; Molecular docking; Molecular Docking Simulation; Molecular dynamics; Molecular Dynamics Simulation; Multidrug resistant organisms; Pathogens; Physicochemical properties; Population genetics; Protein binding; Proteins; Proteomes; Proteomics; Proteomics - methods; Public health; Salmonella; Salmonella - genetics; Salmonella - immunology; Salmonella food poisoning; Salmonella Infections - immunology; Salmonella Infections - microbiology; Salmonella Infections - prevention & control; Salmonella Vaccines - immunology; T cells; Toll-like receptors; Typhoid; Vaccines; Wildlife conservation
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0292413

Salmonella infections pose a significant global public health concern due to the substantial expenses associated with monitoring, preventing, and treating the infection. In this study, we explored the core proteome of Salmonella to design a multi-epitope vaccine through Subtractive Proteomics and immunoinformatics approaches. A total of 2395 core proteins were curated from 30 different isolates of Salmonella (strain NZ CP014051 was taken as reference). Utilizing the subtractive proteomics approach on the Salmonella core proteome, Curlin major subunit A (CsgA) was selected as the vaccine candidate. csgA is a conserved gene that is related to 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 multi-epitope vaccine was constructed with peptide linkers and Human Beta Defensin-2 (as an adjuvant). The vaccine could be highly antigenic, non-toxic, non-allergic, and have suitable physicochemical properties. Additionally, Molecular Dynamics Simulation and Immune Simulation demonstrated that the vaccine can bind with Toll Like Receptor 4 and elicit a robust immune response. Using in vitro, in vivo, and clinical trials, our findings could yield a Pan-Salmonella vaccine that might provide protection against various Salmonella species.