Designing a Recombinant Vaccine against Providencia rettgeri Using Immunoinformatics Approach

Abstract

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.

Designing of a Recombinant Multi-Epitopes Based Vaccine against Enterococcus mundtii Using Bioinformatics and Immunoinformatics Approaches

“…The host non-homologous proteins provide the opportunity to avoid autoimmune reactions [ 52 ]. Similarly, a lesser number of transmembrane helices ensures only those proteins should be selected, which can be easily cloned and expressed [ 18 ].…”

“…Furthermore, virulent proteins can stimulate and generate a proper immune response, so virulent proteins were predicted using a VFDB analysis. For an easy experimental analysis and cloning and expression analysis, all the proteins were discarded, having more than one transmembrane helix [ 18 ]. Moreover, an antigenicity, allergenicity, and homology analysis were conducted following the same methodology of Khan et al 2020 [ 46 ].…”

“…Moreover, physicochemical properties of the designed multi-epitope vaccine construct were evaluated using ProtParam Expassy [ 30 ]. Additionally, the designed vaccine model was then subjected to loop modelling, loops refinement, in silico codon optimization, and cloning to check the maximum level of expression [ 18 ].…”

“…Different computational multi-epitope vaccines have been designed against different bacterial pathogens, such as Morganella morganii [ 16 ], Acinetobacter baumannii , Pseudomonas aeruginosa and Providencia rettgeri , etc. [ 17 , 18 ]. An ideal multi-epitope vaccine construct consists of a series of overlapping epitopes.…”

Whole Proteome-Based Therapeutic Targets Annotation and Designing of Multi-Epitope-Based Vaccines against the Gram-Negative XDR-Alcaligenes faecalis Bacterium

“…Furthermore, the MM-GBSA analysis was also performed for both of the docking complexes to curate individual binding free energies, as reported in previous studies [ 64 , 65 , 66 , 67 ]. This included depiction of van der Waals energy, electrostatic energy, Gibbs free energy, surface area, and the total binding energy to evaluate the interaction capacity of the two MEVCs with human TLR-2, as shown in Table S2 .…”