Identification of potential candidate vaccines against Mycobacterium ulcerans based on the major facilitator superfamily transporter protein
Buruli ulcer is a neglected tropical disease that is characterized by non-fatal lesion development. The causative agent is Mycobacterium ulcerans (M. ulcerans). There are no known vectors or transmission methods, preventing the development of control methods. There are effective diagnostic technique...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-11-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1023558/full |
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| author | Tamara Z. Ishwarlall Victoria T. Adeleke Leah Maharaj Moses Okpeku Adebayo A. Adeniyi Adebayo A. Adeniyi Matthew A. Adeleke |
| author_facet | Tamara Z. Ishwarlall Victoria T. Adeleke Leah Maharaj Moses Okpeku Adebayo A. Adeniyi Adebayo A. Adeniyi Matthew A. Adeleke |
| author_sort | Tamara Z. Ishwarlall |
| collection | DOAJ |
| description | Buruli ulcer is a neglected tropical disease that is characterized by non-fatal lesion development. The causative agent is Mycobacterium ulcerans (M. ulcerans). There are no known vectors or transmission methods, preventing the development of control methods. There are effective diagnostic techniques and treatment routines; however, several socioeconomic factors may limit patients’ abilities to receive these treatments. The Bacillus Calmette–Guérin vaccine developed against tuberculosis has shown limited efficacy, and no conventionally designed vaccines have passed clinical trials. This study aimed to generate a multi-epitope vaccine against M. ulcerans from the major facilitator superfamily transporter protein using an immunoinformatics approach. Twelve M. ulcerans genome assemblies were analyzed, resulting in the identification of 11 CD8+ and 7 CD4+ T-cell epitopes and 2 B-cell epitopes. These conserved epitopes were computationally predicted to be antigenic, immunogenic, non-allergenic, and non-toxic. The CD4+ T-cell epitopes were capable of inducing interferon-gamma and interleukin-4. They successfully bound to their respective human leukocyte antigens alleles in in silico docking studies. The expected global population coverage of the T-cell epitopes and their restricted human leukocyte antigens alleles was 99.90%. The population coverage of endemic regions ranged from 99.99% (Papua New Guinea) to 21.81% (Liberia). Two vaccine constructs were generated using the Toll-like receptors 2 and 4 agonists, LprG and RpfE, respectively. Both constructs were antigenic, non-allergenic, non-toxic, thermostable, basic, and hydrophilic. The DNA sequences of the vaccine constructs underwent optimization and were successfully in-silico cloned with the pET-28a(+) plasmid. The vaccine constructs were successfully docked to their respective toll-like receptors. Molecular dynamics simulations were carried out to analyze the binding interactions within the complex. The generated binding energies indicate the stability of both complexes. The constructs generated in this study display severable favorable properties, with construct one displaying a greater range of favorable properties. However, further analysis and laboratory validation are required. |
| first_indexed | 2024-04-13T21:39:20Z |
| format | Article |
| id | doaj.art-ddbd41c4fc954a15b8ef8234fb04ced1 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-13T21:39:20Z |
| publishDate | 2022-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-ddbd41c4fc954a15b8ef8234fb04ced12022-12-22T02:28:49ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-11-011310.3389/fimmu.2022.10235581023558Identification of potential candidate vaccines against Mycobacterium ulcerans based on the major facilitator superfamily transporter proteinTamara Z. Ishwarlall0Victoria T. Adeleke1Leah Maharaj2Moses Okpeku3Adebayo A. Adeniyi4Adebayo A. Adeniyi5Matthew A. Adeleke6Discipline of Genetics, School of Life Sciences, University of KwaZulu-Natal, Durban, South AfricaDepartment of Chemical Engineering, Mangosuthu University of Technology, Durban, South AfricaDiscipline of Genetics, School of Life Sciences, University of KwaZulu-Natal, Durban, South AfricaDiscipline of Genetics, School of Life Sciences, University of KwaZulu-Natal, Durban, South AfricaDepartment of Chemistry, Faculty of Natural and Agricultural Sciences, University of the Free State, Bloemfontein, South AfricaDepartment of Industrial Chemistry, Federal University Oye Ekiti, Oye-Ekiti, Ekiti State, NigeriaDiscipline of Genetics, School of Life Sciences, University of KwaZulu-Natal, Durban, South AfricaBuruli ulcer is a neglected tropical disease that is characterized by non-fatal lesion development. The causative agent is Mycobacterium ulcerans (M. ulcerans). There are no known vectors or transmission methods, preventing the development of control methods. There are effective diagnostic techniques and treatment routines; however, several socioeconomic factors may limit patients’ abilities to receive these treatments. The Bacillus Calmette–Guérin vaccine developed against tuberculosis has shown limited efficacy, and no conventionally designed vaccines have passed clinical trials. This study aimed to generate a multi-epitope vaccine against M. ulcerans from the major facilitator superfamily transporter protein using an immunoinformatics approach. Twelve M. ulcerans genome assemblies were analyzed, resulting in the identification of 11 CD8+ and 7 CD4+ T-cell epitopes and 2 B-cell epitopes. These conserved epitopes were computationally predicted to be antigenic, immunogenic, non-allergenic, and non-toxic. The CD4+ T-cell epitopes were capable of inducing interferon-gamma and interleukin-4. They successfully bound to their respective human leukocyte antigens alleles in in silico docking studies. The expected global population coverage of the T-cell epitopes and their restricted human leukocyte antigens alleles was 99.90%. The population coverage of endemic regions ranged from 99.99% (Papua New Guinea) to 21.81% (Liberia). Two vaccine constructs were generated using the Toll-like receptors 2 and 4 agonists, LprG and RpfE, respectively. Both constructs were antigenic, non-allergenic, non-toxic, thermostable, basic, and hydrophilic. The DNA sequences of the vaccine constructs underwent optimization and were successfully in-silico cloned with the pET-28a(+) plasmid. The vaccine constructs were successfully docked to their respective toll-like receptors. Molecular dynamics simulations were carried out to analyze the binding interactions within the complex. The generated binding energies indicate the stability of both complexes. The constructs generated in this study display severable favorable properties, with construct one displaying a greater range of favorable properties. However, further analysis and laboratory validation are required.https://www.frontiersin.org/articles/10.3389/fimmu.2022.1023558/fullBuruli ulcerimmunoinformaticsmulti-epitope-based vaccineMycobacterium ulceransneglected tropical disease |
| spellingShingle | Tamara Z. Ishwarlall Victoria T. Adeleke Leah Maharaj Moses Okpeku Adebayo A. Adeniyi Adebayo A. Adeniyi Matthew A. Adeleke Identification of potential candidate vaccines against Mycobacterium ulcerans based on the major facilitator superfamily transporter protein Frontiers in Immunology Buruli ulcer immunoinformatics multi-epitope-based vaccine Mycobacterium ulcerans neglected tropical disease |
| title | Identification of potential candidate vaccines against Mycobacterium ulcerans based on the major facilitator superfamily transporter protein |
| title_full | Identification of potential candidate vaccines against Mycobacterium ulcerans based on the major facilitator superfamily transporter protein |
| title_fullStr | Identification of potential candidate vaccines against Mycobacterium ulcerans based on the major facilitator superfamily transporter protein |
| title_full_unstemmed | Identification of potential candidate vaccines against Mycobacterium ulcerans based on the major facilitator superfamily transporter protein |
| title_short | Identification of potential candidate vaccines against Mycobacterium ulcerans based on the major facilitator superfamily transporter protein |
| title_sort | identification of potential candidate vaccines against mycobacterium ulcerans based on the major facilitator superfamily transporter protein |
| topic | Buruli ulcer immunoinformatics multi-epitope-based vaccine Mycobacterium ulcerans neglected tropical disease |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1023558/full |
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