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

Alharbi, Metab; Alshammari, Abdulrahman; Alasmari, Abdullah F.; Alharbi, Salman Mansour; Qamar, Muhammad Tahir ul; Ullah, Asad; Ahmad, Sajjad; Irfan, Muhammad

doi:10.3390/ijerph19063729

Cited by 31 publications

(26 citation statements)

References 67 publications

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“…Targets were identified that could be part of the pathogen core proteome and nonredundant. Extracellular proteins being surface proteins were used and subjected to different vaccine filters to obtain the potential targets [ 76 ]. Proteins were examined for the presence of transmembrane helices, allergenicity, antigenicity, and physicochemical properties to screen experimental, feasible, and effective vaccine targets [ 77 ].…”

Section: Discussionmentioning

confidence: 99%

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Design of a Multi-Epitope Vaccine against Tropheryma whipplei Using Immunoinformatics and Molecular Dynamics Simulation Techniques

et al. 2022

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Whipple’s disease is caused by T. whipplei, a Gram-positive pathogenic bacterium. It is considered a persistent infection affecting various organs, more likely to infect males. There is currently no licensed vaccination available for Whipple’s disease; thus, the development of a chimeric peptide-based vaccine against T. whipplei has the potential to be tremendously beneficial in preventing Whipple’s disease in the future. The present study aimed to apply modern computational approaches to generate a multi-epitope-based vaccine that expresses antigenic determinants prioritized from the core proteome of two T. whipplei whole proteomes. Using an integrated computational approach, four immunodominant epitopes were found from two extracellular proteins. Combined, these epitopes covered 89.03% of the global population. The shortlisted epitopes exhibited a strong binding affinity for the B- and T-cell reference set of alleles, high antigenicity score, nonallergenic nature, high solubility, nontoxicity, and excellent binders of DRB1*0101. Through the use of appropriate linkers and adjuvation with a suitable adjuvant molecule, the epitopes were designed into a chimeric vaccine. An adjuvant was linked to the connected epitopes to boost immunogenicity and efficiently engage both innate and adaptive immunity. The physiochemical properties of the vaccine were observed favorable, leading toward the 3D modeling of the construct. Furthermore, the vaccine’s binding confirmation to the TLR-4 critical innate immune receptor was also determined using molecular docking and molecular dynamics (MD) simulations, which shows that the vaccine has a strong binding affinity for TLR4 (−29.4452 kcal/mol in MM-GBSA and −42.3229 kcal/mol in MM-PBSA). Overall, the vaccine described here has a promising potential for eliciting protective and targeted immunogenicity, subject to further experimental testing.

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Section: Discussionmentioning

confidence: 99%

“…Epitope mapping of the selected core proteins was performed via immunoinformatic tools/server, and ten led to epitope prioritization [ 76 ]. B-cell-derived T-cell epitopes were predicted and selected on the basis of their antigenicity, nonallergenicity, solubility, and nontoxicity potential to be a part of the MEPTWV.…”

Section: Discussionmentioning

confidence: 99%

Design of a Multi-Epitope Vaccine against Tropheryma whipplei Using Immunoinformatics and Molecular Dynamics Simulation Techniques

et al. 2022

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“…Afterward, several filters were applied on the selected outer membrane, extracellular and periplasmic proteins to perform selection of potential vaccine targets. Proteins that play a significant role in pathogenesis are prime targets for vaccine design ( Ahmad et al, 2019 ; Alharbi et al, 2022a ). A BLASTp search was conducted against the core virulent factor database (VFDB) ( Liu et al, 2019 ) using output proteins from the subcellular localization step, and those with sequence identities of ≥ 30% and bit scores ≥ 100 were selected ( Qamar et al, 2021 ).…”

Section: Methodsmentioning

confidence: 99%

Reverse Vaccinology and Immunoinformatic Assisted Designing of a Multi-Epitopes Based Vaccine Against Nosocomial Burkholderia cepacia

2022

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Burkholderia cepacia is a Gram-negative nosocomial pathogen and is considered as a troublesome bacterium due to its resistance to many common antibiotics. There is no licensed vaccine available to prevent the pathogen infections, thus making the condition more alarming and warrant the search for novel therapeutic and prophylactic approaches. In order to identify protective antigens from pathogen proteome, substantial efforts are put forth to prioritized potential vaccine targets and antigens that can be easily evaluated experimentally. In this vaccine design investigation, it was found that B. cepacia completely sequenced proteomes available in NCBI genome database has a total of 28,966 core proteins. Out of total, 25,282 proteins were found redundant while 3,684 were non-redundant. Subcellular localization revealed that 18 proteins were extracellular, 31 were part of the outer membrane, 75 proteins were localized in the periplasm, and 23 were virulent proteins. Five proteins namely flagellar hook protein (FlgE), fimbria biogenesis outer membrane usher protein, Type IV pilus secretin (PilQ), cytochrome c4, flagellar hook basal body complex protein (FliE) were tested for positive for antigenic, non-toxic, and soluble epitopes during predication of B-cell derived T-cell epitopes. A vaccine peptide of 14 epitopes (joined together via GPGPG linkers) and cholera toxin B subunit (CTBS) adjuvant (joined to epitopes peptide via EAAAK linker) was constructed. Binding interaction of the modeled vaccine with MHC-I, MHC-II, and Toll-like receptor 4 (TLR-4) immune receptors was studied using molecular docking studies and further analyzed in molecular dynamics simulations that affirms strong intermolecular binding and stable dynamics. The maximum root mean square deviation (RMSD) score of complexes in the simulation time touches to 2 Å. Additionally, complexes binding free energies were determined that concluded robust interaction energies dominated by van der Waals. The total energy of each complex is < −190 kcal/mol. In summary, the designed vaccine showed promising protective immunity against B. cepacia and needs to be examined in experiments.

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“…The linkers used prevent epitopes from folding over one another and keep the epitopes separated so they can be easily presented to the host immune system [35]. After the construction of the vaccine construct, the physicochemical properties were analyzed for the designed vaccine construct using Protparam [41].…”

Section: Multi-epitope-based Vaccine Designing and Processing Phasementioning

confidence: 99%

Computer-Aided Multi-Epitope Vaccine Design against Enterobacter xiangfangensis

Alshammari

Alharbi

Al-Ghamdi

et al. 2022

IJERPH

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Antibiotic resistance is a global public health threat and is associated with high mortality due to antibiotics’ inability to treat bacterial infections. Enterobacter xiangfangensis is an emerging antibiotic-resistant bacterial pathogen from the Enterobacter genus and has the ability to acquire resistance to multiple antibiotic classes. Currently, there is no effective vaccine against Enterobacter species. In this study, a chimeric vaccine is designed comprising different epitopes screened from E. xiangfangensis proteomes using immunoinformatic and bioinformatic approaches. In the first phase, six fully sequenced proteomes were investigated by bacterial pan-genome analysis, which revealed that the pathogen consists of 21,996 core proteins, 3785 non-redundant proteins and 18,211 redundant proteins. The non-redundant proteins were considered for the vaccine target prioritization phase where different vaccine filters were applied. By doing so, two proteins; ferrichrome porin (FhuA) and peptidoglycan-associated lipoprotein (Pal) were shortlisted for epitope prediction. Based on properties of antigenicity, allergenicity, water solubility and DRB*0101 binding ability, three epitopes (GPAPTIAAKR, ATKTDTPIEK and RNNGTTAEI) were used in multi-epitope vaccine designing. The designed vaccine construct was analyzed in a docking study with immune cell receptors, which predicted the vaccine’s proper binding with said receptors. Molecular dynamics analysis revealed that the vaccine demonstrated stable binding dynamics, and binding free energy calculations further validated the docking results. In conclusion, these in silico results may help experimentalists in developing a vaccine against E. xiangfangensis in specific and Enterobacter in general.

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

Cited by 31 publications

References 67 publications

Design of a Multi-Epitope Vaccine against Tropheryma whipplei Using Immunoinformatics and Molecular Dynamics Simulation Techniques

Design of a Multi-Epitope Vaccine against Tropheryma whipplei Using Immunoinformatics and Molecular Dynamics Simulation Techniques

Reverse Vaccinology and Immunoinformatic Assisted Designing of a Multi-Epitopes Based Vaccine Against Nosocomial Burkholderia cepacia

Computer-Aided Multi-Epitope Vaccine Design against Enterobacter xiangfangensis

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