Design of a multi-epitope vaccine against drug-resistant mycobacterium tuberculosis and mycobacterium bovis using reverse vaccinology
Abstract The global burden of Mycobacterium tuberculosis (M. tuberculosis) and Mycobacterium bovis (M. bovis), the rise of drug-resistant strains, necessitates an urgent need for developing more effective vaccines. This study employed an in-silico approach to design a multi-epitope vaccine targeting...
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Nature Portfolio
2025-07-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-025-11768-3 |
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| author | Eva Akurut Yahaya Gavamukulya Julius Mulindwa Moses Isiagi Ronald Galiwango Mudarshiru Bbuye Ibra Lujumba Davis Kiberu Patricia Nabisubi Grace Kebirungi Andrew Kambugu Barbara Castelnuovo Gyaviira Nkurunungi Daudi Jjingo Brenda Oketch David Patrick Kateete Gerald Mboowa |
| author_facet | Eva Akurut Yahaya Gavamukulya Julius Mulindwa Moses Isiagi Ronald Galiwango Mudarshiru Bbuye Ibra Lujumba Davis Kiberu Patricia Nabisubi Grace Kebirungi Andrew Kambugu Barbara Castelnuovo Gyaviira Nkurunungi Daudi Jjingo Brenda Oketch David Patrick Kateete Gerald Mboowa |
| author_sort | Eva Akurut |
| collection | DOAJ |
| description | Abstract The global burden of Mycobacterium tuberculosis (M. tuberculosis) and Mycobacterium bovis (M. bovis), the rise of drug-resistant strains, necessitates an urgent need for developing more effective vaccines. This study employed an in-silico approach to design a multi-epitope vaccine targeting the PE_PGRS16 protein, a conserved virulence factor found across both species, including drug-resistant strains. PE_PGRS16 was chosen due to its extracellular localization, adhesion properties, and virulence characteristics, making it a promising vaccine target. Epitopes for B-cells, Cytotoxic T Lymphocytes, and Helper T Lymphocytes were selected based on antigenicity, non-toxicity, and immune response potential. The vaccine construct demonstrated favorable properties, including high antigenicity, solubility, and stability, with a low instability index (-31.31) and binding energy (-44.566) when docked to TLR4, suggesting its potential for immune activation. Griselimycin was incorporated as an adjuvant to enhance immunogenicity, as predicted by C-ImmSim simulations. Population coverage analysis for East Africa revealed high applicability, with 98.35% coverage for Class I epitopes, 100% coverage for Class II epitopes, and 100% combined coverage, with average hit values of 8.4, 12.26, and 20.66, respectively. These results suggest broad potential for global vaccine deployment. This study presents a novel multi-epitope vaccine targeting PE_PGRS16, with the potential to combat Mycobacterium tuberculosis and Mycobacterium bovis infections, including drug-resistant forms. Further experimental validation is necessary to confirm its efficacy and safety. |
| format | Article |
| id | doaj-art-fa65aed6dfbb4a2c853af06d8f4f4524 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-fa65aed6dfbb4a2c853af06d8f4f45242025-08-20T03:46:04ZengNature PortfolioScientific Reports2045-23222025-07-0115111710.1038/s41598-025-11768-3Design of a multi-epitope vaccine against drug-resistant mycobacterium tuberculosis and mycobacterium bovis using reverse vaccinologyEva Akurut0Yahaya Gavamukulya1Julius Mulindwa2Moses Isiagi3Ronald Galiwango4Mudarshiru Bbuye5Ibra Lujumba6Davis Kiberu7Patricia Nabisubi8Grace Kebirungi9Andrew Kambugu10Barbara Castelnuovo11Gyaviira Nkurunungi12Daudi Jjingo13Brenda Oketch14David Patrick Kateete15Gerald Mboowa16Department of Immunology and Molecular Biology, College of Health Sciences, Makerere UniversityDepartment of Biochemistry and Molecular Biology, Faculty of Health Sciences, Busitema UniversityDepartment of Biochemistry and Sports Science, College of Natural Sciences, Makerere UniversityDepartment of Medicine, Division of Pulmonology, University of Cape TownThe African Center of Excellence in Bioinformatics and Data-Intensive SciencesVaccine and Epidemics Research group, College of Health Sciences, Makerere University Lung InstituteThe African Center of Excellence in Bioinformatics and Data-Intensive SciencesDepartment of Immunology and Molecular Biology, College of Health Sciences, Makerere UniversityDepartment of Immunology and Molecular Biology, College of Health Sciences, Makerere UniversityThe African Center of Excellence in Bioinformatics and Data-Intensive SciencesThe Infectious Diseases Institute, Makerere UniversityThe Infectious Diseases Institute, Makerere UniversityMedical Research Council, School of Hygiene and Tropical Medicine, Virus Research Institute and LondonThe African Center of Excellence in Bioinformatics and Data-Intensive SciencesMedical Research Council, Virus Research Institute and London School of Hygiene & Tropical Medicine Uganda Research Unit | International AIDS Vaccine InitiativeDepartment of Immunology and Molecular Biology, College of Health Sciences, Makerere UniversityThe African Center of Excellence in Bioinformatics and Data-Intensive SciencesAbstract The global burden of Mycobacterium tuberculosis (M. tuberculosis) and Mycobacterium bovis (M. bovis), the rise of drug-resistant strains, necessitates an urgent need for developing more effective vaccines. This study employed an in-silico approach to design a multi-epitope vaccine targeting the PE_PGRS16 protein, a conserved virulence factor found across both species, including drug-resistant strains. PE_PGRS16 was chosen due to its extracellular localization, adhesion properties, and virulence characteristics, making it a promising vaccine target. Epitopes for B-cells, Cytotoxic T Lymphocytes, and Helper T Lymphocytes were selected based on antigenicity, non-toxicity, and immune response potential. The vaccine construct demonstrated favorable properties, including high antigenicity, solubility, and stability, with a low instability index (-31.31) and binding energy (-44.566) when docked to TLR4, suggesting its potential for immune activation. Griselimycin was incorporated as an adjuvant to enhance immunogenicity, as predicted by C-ImmSim simulations. Population coverage analysis for East Africa revealed high applicability, with 98.35% coverage for Class I epitopes, 100% coverage for Class II epitopes, and 100% combined coverage, with average hit values of 8.4, 12.26, and 20.66, respectively. These results suggest broad potential for global vaccine deployment. This study presents a novel multi-epitope vaccine targeting PE_PGRS16, with the potential to combat Mycobacterium tuberculosis and Mycobacterium bovis infections, including drug-resistant forms. Further experimental validation is necessary to confirm its efficacy and safety.https://doi.org/10.1038/s41598-025-11768-3Mycobacterium tuberculosisMycobacterium bovisVaccinesBCGReverse vaccinologyMolecular Docking |
| spellingShingle | Eva Akurut Yahaya Gavamukulya Julius Mulindwa Moses Isiagi Ronald Galiwango Mudarshiru Bbuye Ibra Lujumba Davis Kiberu Patricia Nabisubi Grace Kebirungi Andrew Kambugu Barbara Castelnuovo Gyaviira Nkurunungi Daudi Jjingo Brenda Oketch David Patrick Kateete Gerald Mboowa Design of a multi-epitope vaccine against drug-resistant mycobacterium tuberculosis and mycobacterium bovis using reverse vaccinology Scientific Reports Mycobacterium tuberculosis Mycobacterium bovis Vaccines BCG Reverse vaccinology Molecular Docking |
| title | Design of a multi-epitope vaccine against drug-resistant mycobacterium tuberculosis and mycobacterium bovis using reverse vaccinology |
| title_full | Design of a multi-epitope vaccine against drug-resistant mycobacterium tuberculosis and mycobacterium bovis using reverse vaccinology |
| title_fullStr | Design of a multi-epitope vaccine against drug-resistant mycobacterium tuberculosis and mycobacterium bovis using reverse vaccinology |
| title_full_unstemmed | Design of a multi-epitope vaccine against drug-resistant mycobacterium tuberculosis and mycobacterium bovis using reverse vaccinology |
| title_short | Design of a multi-epitope vaccine against drug-resistant mycobacterium tuberculosis and mycobacterium bovis using reverse vaccinology |
| title_sort | design of a multi epitope vaccine against drug resistant mycobacterium tuberculosis and mycobacterium bovis using reverse vaccinology |
| topic | Mycobacterium tuberculosis Mycobacterium bovis Vaccines BCG Reverse vaccinology Molecular Docking |
| url | https://doi.org/10.1038/s41598-025-11768-3 |
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