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

Abstract

<jats:title>ABSTRACT</jats:title><jats:p>In 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 <jats:italic>Mycobacterium avium hominissuis</jats:italic> 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.</jats:p>

Proteome-wide Analysis of Coxiella burnetii for Conserved T-cell epitopes with Presentation Across Multiple Host Species

“…It is likely that there is a secondary processing step that is not recognized by Inmembrane. This does not disqualify the overall purpose for such notation, as many vaccination efforts have focused on surface proteins, where it is believed that these proteins most readily interact with the immune system during infection (1,25,53). While care should be taken regarding protein location, proteins residing at the level of the membrane or that are secreted would suggest improved immune recognition.…”

“…Bioinformatic tools have been developed to more quickly and cost effectively assess proteins as host antigens (20)(21)(22)(23). This strategy is known as reverse vaccination development, wherein in silico methods cut down the number of initial screening experiments required to identify putative stimulants of the adaptive immune response (20,24,25). In silico techniques assess the antigenic ability of peptides by modeling their potential immune system interactions as Tor B-cell epitopes (20,22).…”

Shotgun Immunoproteomic Approach for the Discovery of Linear B Cell Epitopes in Biothreat Agents Francisella tularensis and Burkholderia pseudomallei

“…In addition to AAACS, we also scored peptides based on how many complete sequenced genomes of pathogenic B. pseudomallei and F. tularensis they occurred in, similar to the conservation analysis in EpitoCore (24). We downloaded proteomes for all 110 B. pseudomallei strains with complete genome sequences available through NCBI.…”

Proteome-wide Epitope Prediction: Leveraging Bioinformatic Technologies in Rational Vaccine Design

“…Labs studying virology-based interaction with the immune system were able to use these programs to identify T-cell epitopes within the entire viral proteome [22]. Due to the size difference between viral and bacterial proteomes, bacteriology-based research continued to narrow the proteins of interest based on other constraints [23][24][25][26]. While this methodology can identify proteins that interact with T-cells over the course of infection, there are likely highly qualified immunogens that will be missed by limiting queried proteins.…”

“…While prior vaccine design studies have commonly employed agent conservation to narrow the proteins of interest, there are many investigations that do not consider host homology [22,24,25]. Homology of agent proteins to the proteins found in host species is important to recognize as sensitization of the host immune system to these macromolecules could cause an autoimmune reaction [28].…”