EpitoCore: mining conserved epitope vaccine candidates in the core proteome of multiple bacteria strains

ABSTRACTIn reverse vaccinology approaches, complete proteomes of bacteria are submitted to multiple computational prediction steps in order to filter proteins that are possible vaccine candidates. Most available tools perform such analysis only in a single strain, or a very limited number of strains. But the vast amount of genomic data had shown that most bacteria contain pangenomes, i.e. their genomic information contains core, conserved genes, and random accessory genes specific to each strain. Therefore, it is of the utmost importance to define core proteins, and also core epitopes, in reverse vaccinology methods. EpitoCore is a decision-tree pipeline developed to fulfill that need. It provides surfaceome prediction of proteins from related strains, defines clusters of core proteins within those, calculate the immunogenicity of such clusters, predicts epitopes for a given set of MHC alleles defined by the user, and then reports if epitopes are located extracellularly and if they are conserved among the core homologues. Pipeline performance is illustrated by mining peptide vaccine candidates in Mycobacterium avium hominissuis strains. From a total proteome of approximately 4,800 proteins per strain, EpitoCore mined 103 highly immunogenic core homologues located at cell surface, many of those related to virulence and drug resistance. Conserved epitopes identified among these homologues allows the users to define sets of peptides with potential to immunize the largest coverage of tested HLA alleles using peptide-based vaccines. Therefore, EpitoCore is able to provide automated identification of conserved epitopes in bacterial pangenomic datasets.

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Identification of Cross-Protective Potential Antigens against PathogenicBrucellaspp. through Combining Pan-Genome Analysis with Reverse Vaccinology

Journal of Immunology Research ◽

10.1155/2018/1474517 ◽

2018 ◽

Vol 2018 ◽

pp. 1-15 ◽

Cited By ~ 6

Author(s):

Yasmin Hisham ◽

Yaqoub Ashhab

Keyword(s):

Brucella Melitensis ◽

Cell Epitope ◽

Reverse Vaccinology ◽

Pathogenic Species ◽

The Core ◽

Protective Antigens ◽

Cumulative Score ◽

Core Proteins ◽

Associated Proteins ◽

Core Proteome

Brucellosis is a zoonotic infectious disease caused by bacteria of the genusBrucella.Brucella melitensis,Brucella abortus, andBrucella suisare the most pathogenic species of this genus causing the majority of human and domestic animal brucellosis. There is a need to develop a safe and potent subunit vaccine to overcome the serious drawbacks of the live attenuatedBrucellavaccines. The aim of this work was to discover antigen candidates conserved among the three pathogenic species. In this study, we employed a reverse vaccinology strategy to compute the core proteome of 90 completed genomes: 55B. melitensis, 17B. abortus, and 18B. suis. The core proteome was analyzed by a metasubcellular localization prediction pipeline to identify surface-associated proteins. The identified proteins were thoroughly analyzed using variousin silicotools to obtain the most potential protective antigens. The number of core proteins obtained from analyzing the 90 proteomes was 1939 proteins. The surface-associated proteins were 177. The number of potential antigens was 87; those with adhesion score ≥ 0.5 were considered antigen with “high potential,” while those with a score of 0.4–0.5 were considered antigens with “intermediate potential.” According to a cumulative score derived from protein antigenicity, density of MHC-I and MHC-II epitopes, MHC allele coverage, and B-cell epitope density scores, a final list of 34 potential antigens was obtained. Remarkably, most of the 34 proteins are associated with bacterial adhesion, invasion, evasion, and adaptation to the hostile intracellular environment of macrophages which is adjusted to depriveBrucellaof required nutrients. Our results provide a manageable list of potential protective antigens for developing a potent vaccine against brucellosis. Moreover, our elaborated analysis can provide further insights into novelBrucellavirulence factors. Our next step is to test some of these antigens using an appropriate antigen delivery system.

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A Comprehensive Computer Aided Vaccine Design Approach to Propose a Multi-Epitopes Subunit Vaccine against Genus Klebsiella Using Pan-Genomics, Reverse Vaccinology, and Biophysical Techniques

Vaccines ◽

10.3390/vaccines9101087 ◽

2021 ◽

Vol 9 (10) ◽

pp. 1087

Author(s):

Khaled S. Allemailem

Keyword(s):

Molecular Dynamics ◽

Binding Free Energy ◽

Water Soluble ◽

Dynamics Simulation ◽

Reverse Vaccinology ◽

World Health ◽

Potential Core ◽

The Core ◽

Core Proteins ◽

Core Proteome

Klebsiella is a genus of nosocomial bacterial pathogens and is placed in the most critical list of World Health Organization (WHO) for development of novel therapeutics. The pathogens of the genus are associated with high mortality and morbidity. Owing to their strong resistance profile against different classes of antibiotics and nonavailability of a licensed vaccine, urgent efforts are required to develop a novel vaccine candidate that can tackle all pathogenic species of the Klebsiella genus. The present study aims to design a broad-spectrum vaccine against all species of the Klebsiella genus with objectives to identify the core proteome of pathogen species, prioritize potential core vaccine proteins, analyze immunoinformatics of the vaccine proteins, construct a multi-epitopes vaccine, and provide its biophysical analysis. Herein, we investigated all reference species of the genus to reveal their core proteome. The core proteins were then subjected to multiple reverse vaccinology checks that are mandatory for the prioritization of potential vaccine candidates. Two proteins (TonB-dependent siderophore receptor and siderophore enterobactin receptor FepA) were found to fulfill all vaccine parameters. Both these proteins harbor several potent B-cell-derived T-cell epitopes that are antigenic, nonallergic, nontoxic, virulent, water soluble, IFN-γ producer, and efficient binder of DRB*0101 allele. The selected epitopes were modeled into a multi-epitope peptide comprising linkers and Cholera Toxin B adjuvant. For docking with innate immune and MHC receptors and afterward molecular dynamics simulations and binding free energy analysis, the vaccine structure was modeled for tertiary structure and refined for structural errors. To assess the binding affinity and presentation of the designed vaccine construct, binding mode and interactions analysis were performed using molecular docking and molecular dynamics simulation techniques. These biophysical approaches illustrated the vaccine as a good binder to the immune receptors and revealed robust interactions energies. The vaccine sequence was further translated to nucleotide sequence and cloned into an appropriate vector for expressing it at high rate in Escherichia coli K12 strain. In addition, the vaccine was illustrated to generate a good level of primary, secondary, and tertiary immune responses, proving good immunogenicity of the vaccine. Based on the reported results, the vaccine can be a good candidate to be evaluated for effectiveness in wet laboratory validation studies.

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Comparative Analysis of the Core Proteomes among the Pseudomonas Major Evolutionary Groups Reveals Species-Specific Adaptations for Pseudomonas aeruginosa and Pseudomonas chlororaphis

Diversity ◽

10.3390/d12080289 ◽

2020 ◽

Vol 12 (8) ◽

pp. 289

Author(s):

Marios Nikolaidis ◽

Dimitris Mossialos ◽

Stephen G. Oliver ◽

Grigorios D. Amoutzias

Keyword(s):

Pseudomonas Aeruginosa ◽

Pseudomonas Syringae ◽

Pseudomonas Stutzeri ◽

Phylogenomic Analysis ◽

Pseudomonas Chlororaphis ◽

Phylogenetic Groups ◽

The Core ◽

Core Proteins ◽

Core Proteome ◽

Species Specific

The Pseudomonas genus includes many species living in diverse environments and hosts. It is important to understand which are the major evolutionary groups and what are the genomic/proteomic components they have in common or are unique. Towards this goal, we analyzed 494 complete Pseudomonas proteomes and identified 297 core-orthologues. The subsequent phylogenomic analysis revealed two well-defined species (Pseudomonas aeruginosa and Pseudomonas chlororaphis) and four wider phylogenetic groups (Pseudomonas fluorescens, Pseudomonas stutzeri, Pseudomonas syringae, Pseudomonas putida) with a sufficient number of proteomes. As expected, the genus-level core proteome was highly enriched for proteins involved in metabolism, translation, and transcription. In addition, between 39–70% of the core proteins in each group had a significant presence in each of all the other groups. Group-specific core proteins were also identified, with P. aeruginosa having the highest number of these and P. fluorescens having none. We identified several P. aeruginosa-specific core proteins (such as CntL, CntM, PlcB, Acp1, MucE, SrfA, Tse1, Tsi2, Tse3, and EsrC) that are known to play an important role in its pathogenicity. Finally, a holin family bacteriocin and a mitomycin-like biosynthetic protein were found to be core-specific for P. cholororaphis and we hypothesize that these proteins may confer a competitive advantage against other root-colonizers.

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EpitoCore: Mining Conserved Epitope Vaccine Candidates in the Core Proteome of Multiple Bacteria Strains

Frontiers in Immunology ◽

10.3389/fimmu.2020.00816 ◽

2020 ◽

Vol 11 ◽

Author(s):

Tayna S. Fiuza ◽

João P. M. S. Lima ◽

Gustavo A. de Souza

Keyword(s):

Epitope Vaccine ◽

Vaccine Candidates ◽

The Core ◽

Core Proteome ◽

Conserved Epitope

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Prediction of Prophylactic Peptide Vaccine Candidates for Human Papillomavirus (HPV): An Immunoinformatics and Reverse Vaccinology Approach

Current Proteomics ◽

10.2174/1570164617999200505095802 ◽

2020 ◽

Vol 17 ◽

Author(s):

Mehreen Ismail ◽

Zureesha Sajid ◽

Amjad Ali ◽

Xiaogang Wu ◽

Syed Aun Muhammad ◽

...

Keyword(s):

T Cells ◽

Human Papillomavirus ◽

T Cell ◽

Binding Affinity ◽

Cd8 T Cells ◽

Reverse Vaccinology ◽

Host Immune System ◽

T Cell Epitopes ◽

Multiple Alleles ◽

Vaccine Candidates

Background: Human Papillomavirus (HPV) is responsible for substantial morbidity and mortality worldwide. We predicted immunogenic promiscuous monovalent and polyvalent T-cell epitopes from the polyprotein of the Human Papillomavirus (HPV) using a range of bioinformatics tools and servers. Methods: We used immunoinformatics and reverse vaccinology-based approaches to design prophylactic peptides by antigenicity analysis, Tcell epitopes prediction, proteasomal and conservancy evaluation, host-pathogen protein interactions, and in silico binding affinity analysis. Results: We found two early proteins (E2 and E6) and two late proteins (L1 and L2) of HPV as potential vaccine candidates. Of these proteins (E2, E6, L1 & L2), 2-epitopes of each candidate protein for multiple alleles of MHC class I and II bearing significant binding affinity (>-6.0 kcal/mole). These potential epitopes for CD4+ and CD8+ T-cells were also linked to design polyvalent construct using GPGPG linkers. Cholera toxin B and mycobacterial heparin-binding hemagglutinin adjuvant with a molecular weight of 12.5 and 18.5 kDa were used for epitopes of CD4+ and CD8+ T-cells respectively. The molecular docking indicated the optimum binding affinity of HPV peptides with MHC molecules. This interaction showed that our predicted vaccine candidates are suitable to trigger the host immune system to prevent HPV infections. Conclusion: The predicted conserved T-cell epitopes would contribute to the imminent design of HPV vaccine candidates, which will be able to induce a broad range of immune-responses in a heterogeneous HLA population.

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