An In-depth Genomic Investigation to Design a Multi-Epitope Based Vaccine against Brucellosis

Abstract Brucella melitensis is a gram-negative coccobacillus that causes brucellosis in humans when they come into contact with infected animal meat or consumed raw milk. The lack of effective treatment and increasing antibiotic resistant patterns shown by B. melitensis warrant the search for novel therapeutic targets. In this study, comprehensive bioinformatics, reverse vaccinology, and biophysics techniques were employed to design a novel multi-epitopes-based vaccine (MEBV) against B. melitensis. Pan-genomics, 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, are antigenic, and are adhesin. Furthermore, B and T cell epitopes were predicted from these target proteins. Highly antigenic, immunogenic, and non-allergenic epitopes were shortlisted and used in the MEBV vaccine design. The designed MEBV also showed stable docked conformation with different immune receptors such as MHC-I, MHC-II, and TLR-4. It was found that all three 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 to be the stabilizing factors of complexes. The designed vaccine contains antigenic epitopes that were filtered using stringent criteria. The vaccine was also predicted to generate promising immunological responses and thus could be an attractive candidate for evaluation in experimental studies.