Pan-Genome Analysis of Oral Bacterial Pathogens to Predict a Potential Novel Multi-Epitopes Vaccine Candidate

Abstract

Porphyromonas gingivalis is a Gram-negative anaerobic bacterium, mainly present in the oral cavity and causes periodontal infections. Currently, no licensed vaccine is available against P. gingivalis and other oral bacterial pathogens. To develop a vaccine against P. gingivalis, herein, we applied a bacterial pan-genome analysis (BPGA) on the bacterial genomes that retrieved a total number of 4908 core proteins, which were further utilized for the identification of good vaccine candidates. After several vaccine candidacy analyses, three proteins, namely lytic transglycosylase domain-containing protein, FKBP-type peptidyl-propyl cis-trans isomerase and superoxide dismutase, were shortlisted for epitopes prediction. In the epitopes prediction phase, different types of B and T-cell epitopes were predicted and only those with an antigenic, immunogenic, non-allergenic, and non-toxic profile were selected. Moreover, all the predicted epitopes were joined with each other to make a multi-epitopes vaccine construct, which was linked further to the cholera toxin B-subunit to enhance the antigenicity of the vaccine. For downward analysis, a three dimensional structure of the designed vaccine was modeled. The modeled structure was checked for binding potency with major histocompatibility complex I (MHC-I), major histocompatibility complex II (MHC-II), and Toll-like receptor 4 (TLR-4) immune cell receptors which revealed that the designed vaccine performed proper binding with respect to immune cell receptors. Additionally, the binding efficacy of the vaccine was validated through a molecular dynamic simulation that interpreted strong intermolecular vaccine–receptor binding and confirmed the exposed situation of vaccine epitopes to the host immune system. In conclusion, the study suggested that the model vaccine construct has the potency to generate protective host immune responses and that it might be a good vaccine candidate for experimental in vivo and in vitro studies.

Bioinformatics and immunoinformatics assisted multiepitope vaccine construct against Burkholderia anthina

“…Next allergenicity analysis was done through the Allertop v.2.0 https://www.ddg-pharmfac.net/AllerTOP/ online web server, Allertop v.2.0 is a free alignment base online tool for in silico prediction of allergen protein sequences based on the main physiochemical characteristics of the proteins, for allergenicity analysis Allertop v.2.0 tool requires proteins sequence in plain text format, and the data set and the result is obtained as a probable allergen or non-allergen ( Gul et al, 2022 ). Transmembrane helices analysis was done to remove proteins having > 1 transmembrane helices for the said analysis TMHMM 2.0 online web server https://services.healthtech.dtu.dk/services/TMHMM-2.0 ,TMHMM is membrane is mainly membrane proteins topology prediction approach on the base of hidden Markov model, this server is required FASTA file of the proteins for analysis of physiochemical properties analysis ( Rida et al, 2022 ). BLASTp analysis was performed using human and normal microbiota analysis to remove human and normal microbiota similar protein sequences, this may help in reducing autoimmunity for this analysis BLASTp server https://blast.ncbi.nlm.nih.gov/Blast.cgi?PAGE=Proteins was used BLASTp server associate the query protein sequences to a protein database and find the homologs and non-homologs proteins sequences ( Ud-Din et al, 2022 ).…”

Proteome-Wide Screening of Potential Vaccine Targets against Brucella melitensis

“…The threshold values were set at 0 and 1. Proteins that were exposed and had values of 0 and 1 were selected [ 32 ].…”

“…In addition, drug-resistant strains of B. melitensis are making the situation worse. Thus, considering this, herein we applied an integrated approach comprising comparative genomics, subtractive proteomics, reverse vaccinology, immunoinformatic, and biophysics techniques to identify protective antigens from B. melitensis completely sequenced genomes and designed a multi-epitopes vaccine [ 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 ]. The designed vaccine construct then was examined for interactions with host immune receptors to check whether the vaccine is able to be presented to the host immunity system.…”

Integrativesubtractive proteomics, immunoinformatics, docking, and simulation approaches reveal candidate vaccine against Sin Nombre orthohantavirus

“…The docked complexes were further refined through the FireDock webserver, and 10 docking complexes were refined (24). On the basis of the lowest binding energy, in the case of vaccines with TLR4 and TLR8, the top complexes were subjected to simulation (25).…”