Design of a novel multi-epitopes vaccine against Escherichia fergusonii: a pan-proteome based in- silico approach

Escherichia fergusonii a gram-negative rod-shaped bacterium in the Enterobacteriaceae family, infect humans, causing serious illnesses such as urinary tract infection, cystitis, biliary tract infection, pneumonia, meningitis, hemolytic uremic syndrome, and death. Initially treatable with penicillin, antibiotic misuse led to evolving resistance, including resistance to colistin, a last-resort drug. With no licensed vaccine, the study aimed to design a multi-epitope vaccine against E. fergusonii. The study started with the retrieval of the complete proteome of all known strains and proceeded to filter the surface exposed virulent proteins. Seventeen virulent proteins (4 extracellular, 4 outer membranes, 9 periplasmic) with desirable physicochemical properties were identified from the complete proteome of known strains. Further, these proteins were processed for B-cell and T-cell epitope mapping. Obtained epitopes were evaluated for antigenicity, allergenicity, solubility, MHC-binding, and toxicity and the filtered epitopes were fused by specific linkers and an adjuvant into a vaccine construct. Structure of the vaccine candidate was predicted and refined resulting in 78.1% amino acids in allowed regions and VERIFY3D score of 81%. Vaccine construct was docked with TLR-4, MHC-I, and MHC-II, showing binding energies of -1040.8 kcal/mol, -871.4 kcal/mol, and -1154.6 kcal/mol and maximum interactions. Further, molecular dynamic simulation of the docked complexes was carried out resulting in a significant stable nature of the docked complexes (high B-factor and deformability values, lower Eigen and high variance values) in terms of intermolecular binding conformation and interactions. The vaccine was also reported to stimulate a variety of immunological pathways after administration. In short, the designed vaccine revealed promising predictions about its immune protective potential against E. fergusonii infections however experimental validation is needed to validate the results.