Towards A Novel Multi-Epitopes Chimeric Vaccine for Simulating Strong Immune Responses and Protection against Morganella morganii

Abstract

Morganella morganii is one of the main etiological agents of hospital-acquired infections and no licensed vaccine is available against the pathogen. Herein, we designed a multi-epitope-based vaccine against M. morganii. Predicted proteins from fully sequenced genomes of the pathogen were subjected to a core sequences analysis, followed by the prioritization of non-redundant, host non-homologous and extracellular, outer membrane and periplasmic membrane virulent proteins as vaccine targets. Five proteins (TonB-dependent siderophore receptor, serralysin family metalloprotease, type 1 fimbrial protein, flagellar hook protein (FlgE), and pilus periplasmic chaperone) were shortlisted for the epitope prediction. The predicted epitopes were checked for antigenicity, toxicity, solubility, and binding affinity with the DRB*0101 allele. The selected epitopes were linked with each other through GPGPG linkers and were joined with the cholera toxin B subunit (CTBS) to boost immune responses. The tertiary structure of the vaccine was modeled and blindly docked with MHC-I, MHC-II, and Toll-like receptors 4 (TLR4). Molecular dynamic simulations of 250 nanoseconds affirmed that the designed vaccine showed stable conformation with the receptors. Further, intermolecular binding free energies demonstrated the domination of both the van der Waals and electrostatic energies. Overall, the results of the current study might help experimentalists to develop a novel vaccine against M. morganii.

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

“…In the multi-epitope vaccine construction phase, a total of 10 epitopes (GPADGRIAS, TTINHGGAQA, SERTALSVTT, GDGGNGGGEV, GIKEPDLEK, KQADDRIEA, QAIGGDTSN, EPLDEQTASR, AQWEPQSIEA, and QPLKFSDFEL) were screened as probable antigenic, non-allergic, non-toxic, and good water-soluble predicted epitopes were joined with each other via “GPGPG” linkers to make a multi-epitope vaccine construct. The designed vaccine construct was additionally linked with CTBS adjuvant to make the construct more potent to stimulate strong immunological responses [ 16 ]. The above mentioned linkers are rigid and avoid folding of the epitopes [ 54 ].…”

“…For further validation of a dynamic behavior of docked molecules, molecular dynamics simulations were applied in which a RMSD, RMSF, and hydrogen binding analysis were conducted [ 68 ]. Previously, [ 16 ] also conducted a molecular dynamics simulation analysis in order to check the dynamic behavior of the docked complexes. Free binding energies also suggested strong binding energies.…”

“…The surface localized proteins are exposed to the host immune system and contain antigenic determinants, thus being considered as the best candidate for vaccine designing. Moreover, they play a vital role in the attachment to host cells, infection, and survival of the pathogen [ 16 ]. In the VFDB analysis, virulent proteins were predicted with a bit score ≥ 100 and sequence identity ≥ 30%.…”

“…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 ].…”

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 .…”