Identification of vaccine candidates against rhodococcus equi by combining pangenome analysis with a reverse vaccinology approach.
Abstract: () is a zoonotic opportunistic pathogen that can cause life-threatening infections. The rapid evolution of multidrug-resistant and the fact that there is no currently licensed effective vaccine against warrant the need for vaccine development. Reverse vaccinology (RV), which involves screening a pathogen's entire genome and proteome using various web-based prediction tools, is considered one of the most effective approaches for identifying vaccine candidates. Here, we performed a pangenome analysis to determine the core proteins of . We then used the RV approach to examine the subcellular localization, host and gut flora homology, antigenicity, transmembrane helices, physicochemical properties, and immunogenicity of the core proteins to select potential vaccine candidates. The vaccine candidates were then subjected to epitope mapping to predict the exposed antigenic epitopes that possess the ability to bind with major histocompatibility complex I/II (MHC I/II) molecules. These vaccine candidates and epitopes will form a library of elements for the development of a polyvalent or universal vaccine against . Sixteen complete proteomes were found to contain 6,238 protein families, and the core proteins consisted of 3,969 protein families (∼63.63% of the pangenome), reflecting a low degree of intraspecies genomic variability. From the pool of core proteins, 483 nonhost homologous membrane and extracellular proteins were screened, and 12 vaccine candidates were finally identified according to their antigenicity, physicochemical properties and other factors. These included four cell wall/membrane/envelope biogenesis proteins; four amino acid transport and metabolism proteins; one cell cycle control, cell division and chromosome partitioning protein; one carbohydrate transport and metabolism protein; one secondary metabolite biosynthesis, transport and catabolism protein; and one defense mechanism protein. All 12 vaccine candidates have an experimentally validated 3D structure available in the protein data bank (PDB). Epitope mapping of the candidates showed that 16 MHC I epitopes and 13 MHC II epitopes with the strongest immunogenicity were exposed on the protein surface, indicating that they could be used to develop a polypeptide vaccine. Thus, we utilized an analytical strategy that combines pangenome analysis and RV to generate a peptide antigen library that simplifies the development of multivalent or universal vaccines against and can be applied to the development of other vaccines.
© 2023 Published by Elsevier Ltd.
Publication Date: 2023-07-25 PubMed ID: 37576287PubMed Central: PMC10413060DOI: 10.1016/j.heliyon.2023.e18623Google Scholar: Lookup
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Summary
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The research aimed at discovering potential vaccine candidates for Rhodococcus equi, a dangerous pathogen, by combining pangenome analysis and reverse vaccinology. The study yielded 12 promising vaccine candidates and created a detailed antigen library to aid in multivalent vaccine development.
Pangenome Analysis and Reverse Vaccinology
- The researchers first conducted a pangenome analysis of Rhodococcus equi to identify its core proteins. Pangenome refers to the entire set of genes in a particular species.
- The identified core proteins were then analyzed through reverse vaccinology (RV). This is a method where the entire genome and proteome of a pathogen is screened using web-based tools to find vaccine candidates.
- Various parameters such as subcellular localization, host and gut flora homology, antigenicity, transmembrane helices, physicochemical properties, and immunogenicity of the proteins were considered during the RV analysis.
Selection of Vaccine Candidates
- After screening 3,969 protein families, the researchers selected 483 nonhost homologous membrane and extracellular proteins as potential vaccine candidates.
- These candidates were further narrowed down to 12 based on their antigenicity, physicochemical properties, and other factors.
- The selected vaccines comprised proteins involved in various cellular processes including cell wall/membrane/envelope biogenesis, amino acid transport and metabolism, cell cycle control, carbohydrate transport and metabolism, secondary metabolite biosynthesis, transport and catabolism, and defense mechanisms.
Epitope Mapping and Antigen Library
- The 12 selected candidates underwent epitope mapping to predict the exposed antigenic epitopes that could efficiently bind with Major Histocompatibility Complex (MHC) I/II molecules.
- The researchers located 16 MHC I epitopes and 13 MHC II epitopes with high immunogenicity on the protein surface, indicating potential utility in polypeptide vaccine creation.
- These candidates and epitopes formed a peptide antigen library. The library is expected to simplify the development of multivalent or universal vaccines against Rhodococcus equi and may also serve as a useful resource in the development of other vaccines.
Cite This Article
APA
Liu L, Yu W, Cai K, Ma S, Wang Y, Ma Y, Zhao H.
(2023).
Identification of vaccine candidates against rhodococcus equi by combining pangenome analysis with a reverse vaccinology approach.
Heliyon, 9(8), e18623.
https://doi.org/10.1016/j.heliyon.2023.e18623 Publication
Researcher Affiliations
- College of Veterinary Medicine, Xinjiang Agricultural University, Urumqi 830052, Xinjiang, China.
- College of Veterinary Medicine, Xinjiang Agricultural University, Urumqi 830052, Xinjiang, China.
- College of Veterinary Medicine, Xinjiang Agricultural University, Urumqi 830052, Xinjiang, China.
- College of Veterinary Medicine, Xinjiang Agricultural University, Urumqi 830052, Xinjiang, China.
- College of Veterinary Medicine, Xinjiang Agricultural University, Urumqi 830052, Xinjiang, China.
- Zhaosu Xiyu Horse Industry Co., Ltd. Zhaosu County 835699, Yili Prefecture, Xinjiang, China.
- College of Veterinary Medicine, Xinjiang Agricultural University, Urumqi 830052, Xinjiang, China.
Conflict of Interest Statement
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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