The design of multiepitope vaccines from plasmids of diarrheagenic Escherichia coli against diarrhoea infection: Immunoinformatics approach |
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| Affiliation: | 1. Department of Epidemiology, Emory University Rollins School of Public Health, Atlanta, GA, USA;2. U.S. Food and Drug Administration, Center for Tobacco Products, Office of Science, Washington, DC, USA;3. Hubert Department of Global Health, Emory University Rollins School of Public Health, Atlanta, GA, USA;4. Children''s Global Health Center, Cincinnati Children''s Hospital Medical Center, Cincinnati, OH, USA;5. Kaiser Permanente Center for Health Research, Atlanta, GA, USA;6. Office of Maternal and Child Health Epidemiology, Maternal and Child Health Section, Division of Health Promotion, Georgia Department of Public Health, USA;7. Emory Vaccine Center, Atlanta, GA, USA;8. Department of Pediatrics, Emory University School of Medicine and Children''s Healthcare of Atlanta, Atlanta, GA, USA |
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| Abstract: | Diarrhoea infection is a major global health public problem and is caused by many organisms including diarrheagenic Escherichia coli pathotypes. The common problem with diarrhoea is the drug resistance of pathogenic bacteria, the most promising alternative means of preventing drug resistance is vaccination. However, there has not been any significant success in the prevention of diarrhoea caused by E. coli through vaccination. Epitope-based vaccine is gaining more attention due to its safety and specificity. Sequence variation of protective antigens of the pathogen has posed a new challenge in the development of epitope-based vaccines against the infection, leading to the necessity of multiepitope based design. In this study, immunoinformatics tools were used to design multiepitope vaccine candidates from plasmid genome sequences of multiple pathotypes of E. coli species involved in diarrhoea infections. The ability of the identified epitopes to be used as a cross-protect multiepitope vaccine was achieved by identifying conserved, immunogenic and antigenic peptides that can elicit CD4+ T-cell, CD8+ T-cell and B-cell and bind to MHC I and II HLA alleles. The molecular docking results of T-cell epitopes showed their well binding affinity to receptive protein and with a wider population coverage. The different multiepitope-based vaccines (MEVCs) candidates were constructed and based on the types of epitope linker they contained. The MEVCs exhibited very good binding interactions with the human immune receptor. Among multiepitope vaccines constructed, MEVC6, MEVCA and MEVCB are more promising as potential vaccine candidates for cross-protection against gastrointestinal infections according to the computational study. It is also hoped that after validation and testing, the predicted multiepitope-based vaccine candidates will probably resolve the challenge of immunological heterogeneity facing enteric vaccine development. |
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