Design of a novel multi-epitopes based vaccine against brucellosis

• Published in: Informatics in medicine unlocked Vol. 39; p. 101276
• Main Authors: Hameed, Alaa R., Mohammed, Bassam Qasim, Jassim, Tabarak Sabah, Alharbi, Metab, Ahmad, Sajjad
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 2023; Elsevier
• Subjects: Brucella melitensis; Brucellosis; Core proteomics; Molecular dynamics simulation; Vaccine; Brucellosis; Vaccine; Core proteomics; Molecular dynamics simulation; Brucella melitensis
• ISSN: 2352-9148; 2352-9148
• DOI: 10.1016/j.imu.2023.101276

Brucella melitensis is a gram-negative coccobacillus that causes brucellosis in humans. The lack of effective treatment and increasing antibiotic-resistant patterns shown by B. melitensis, warrant the search for novel therapeutics. In this study, comprehensive bioinformatics, reverse vaccinology, and biophysics techniques were employed to design a novel multi-epitopes based vaccine (MEBV) against B. melitensis. Core proteomics, subtractive proteomics and immunoinformatic studies revealed three core proteins: Flagellar hook protein (FlgE), TonB-dependent receptor, and Porin family protein as promising vaccine targets. The proteins have exposed topology, and are antigenic, and adhesive. Furthermore, B and T cell epitopes were predicted from these proteins. Highly antigenic, immunogenic, non-toxic and non-allergenic epitopes were shortlisted and used in the MEBV design. The designed MEBV also showed stable docked conformation with different immune receptors such as MHC-I, MHC-II, and TLR-4. The global energy of selected docked complexes was as; solution 4 of MEBV-TLR-4 (−45.73 kJ/mol), solution 5 of MEBV-MHC-I (−20.94 kJ/mol), and solution 1 of MEBV-MHC-II (−3.45 kJ/mol). Molecular dynamics simulation studies unveiled a steady root mean square deviation (RMSD) pattern for the systems. However, all of them were stable in terms of intermolecular binding conformation and chemical interactions. Further, the systems showed robust binding energies with net binding energy < −300 kcal/mol. The van der Waals and electrostatic energies were the dominating energies and were found as intermolecular stabilizing factors. The vaccine was also predicted to generate promising immunological responses and thus could be an attractive candidate to be evaluated in experimental studies. [Display omitted] •Flagellar hook protein, TonB-dependent receptor, and Porin family protein as promising vaccine targets.•Designed vaccine showed stable docking conformation with MHC-I, MHC-II, and TLR-4.•The vaccine showed strong electrostatic and van der Waals interactions with receptors.