Designing a Recombinant Vaccine against Providencia rettgeri Using Immunoinformatics Approach

Antibiotic resistance (AR) is the resistance mechanism pattern in bacteria that evolves over some time, thus protecting the bacteria against antibiotics. AR is due to bacterial evolution to make itself fit to changing environmental conditions in a quest for survival of the fittest. AR has emerged due to the misuse and overuse of antimicrobial drugs, and few antibiotics are now left to deal with these superbug infections. To combat AR, vaccination is an effective method, used either therapeutically or prophylactically. In the current study, an in silico approach was applied for the design of multi-epitope-based vaccines against Providencia rettgeri, a major cause of traveler's diarrhea. A total of six proteins: fimbrial protein, flagellar hook protein (FlgE), flagellar basal body L-ring protein (FlgH), flagellar hook-basal body complex protein (FliE), flagellar basal body P-ring formation protein (FlgA), and Gram-negative pili assembly chaperone domain proteins, were considered as vaccine targets and were utilized for B- and T-cell epitope prediction. The predicted epitopes were assessed for allergenicity, antigenicity, virulence, toxicity, and solubility. Moreover, filtered epitopes were utilized in multi-epitope vaccine construction. The predicted epitopes were joined with each other through specific GPGPG linkers and were joined with cholera toxin B subunit adjuvant via another EAAAK linker in order to enhance the efficacy of the designed vaccine. Docking studies of the designed vaccine construct were performed with MHC-I (PDB ID: 1I1Y), MHC-II (1KG0), and TLR-4 (4G8A). Findings of the docking study were validated through molecular dynamic simulations, which confirmed that the designed vaccine showed strong interactions with the immune receptors, and that the epitopes were exposed to the host immune system for proper recognition and processing. Additionally, binding free energies were estimated, which highlighted both electrostatic energy and van der Waals forces to make the complexes stable. Briefly, findings of the current study are promising and may help experimental vaccinologists to formulate a novel multi-epitope vaccine against P. rettgeri.