In silico multi-epitope-based vaccine design for Mycobacterium avium complex species
IntroductionThe Mycobacterium avium complex (MAC)—comprising M. colombiense, M. avium, andM. intracellulare—is an emerging group of opportunistic pathogens responsible for significant morbidity and mortality, particularly in immunocompromised individuals. Despite this growing burden, no vaccines cur...
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Frontiers Media S.A.
2025-06-01
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| author | Leah Kashiri Wonderful T. Choga Wonderful T. Choga Wonderful T. Choga Tinashe Musasa Pasipanodya Nziramasanga Rutendo B. Gutsire Lynn S. Zijenah Norman L. Mukarati Simani Gaseitsiwe Simani Gaseitsiwe Sikhulile Moyo Sikhulile Moyo Sikhulile Moyo Sikhulile Moyo Nyasha Chin’ombe |
| author_facet | Leah Kashiri Wonderful T. Choga Wonderful T. Choga Wonderful T. Choga Tinashe Musasa Pasipanodya Nziramasanga Rutendo B. Gutsire Lynn S. Zijenah Norman L. Mukarati Simani Gaseitsiwe Simani Gaseitsiwe Sikhulile Moyo Sikhulile Moyo Sikhulile Moyo Sikhulile Moyo Nyasha Chin’ombe |
| author_sort | Leah Kashiri |
| collection | DOAJ |
| description | IntroductionThe Mycobacterium avium complex (MAC)—comprising M. colombiense, M. avium, andM. intracellulare—is an emerging group of opportunistic pathogens responsible for significant morbidity and mortality, particularly in immunocompromised individuals. Despite this growing burden, no vaccines currently provide cross-species protection. In silico vaccine design offers a rapid, cost-effective strategy to identify immunogenic epitopes and assemble multi-epitope constructs with optimized safety and efficacy. Accordingly, we aimed to develop a candidate multi-epitope vaccine (MEV) targeting conserved antigens across multiple MAC species.MethodsFrom a genomic survey of nontuberculous mycobacteria (NTM) in Zimbabwe, we assembled complete genomes for M. colombiense (MCOL), M. avium (MAV), and M. intracellulare (MINT). Using both local and global reference datasets, we screened the conserved immunodominant proteins 85A, 85B, and 85C for high-affinity T-helper lymphocyte (THL) epitopes. Promising epitopes were further evaluated for antigenicity, immunogenicity, physicochemical stability, and population coverage.ResultsEpitope mapping across the nine target proteins yielded 82 THL epitopes predicted to bind 13 MHC class II (DRB*) alleles, ensuring broad coverage within Zimbabwean and pan-African populations. Clustering analyses consolidated 26 unique epitopes into 11 consensus peptides, 65.4% of which derived from the 85B proteins. In silico immune simulations predicted robust humoral and cellular responses, including elevated IgG titers, T-helper and T-cytotoxic cell proliferation and increased secretion of IFN-γ and IL-2 following MEV administration.ConclusionThese findings indicate that our construct possesses strong immunogenic potential and cross-species applicability. We present here a rationally designed MEV candidate that merits further experimental validation as a broad-spectrum vaccine against multiple MAC species. |
| format | Article |
| id | doaj-art-d619b891c1ac4b218a2c2b9f32cdde15 |
| institution | OA Journals |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj-art-d619b891c1ac4b218a2c2b9f32cdde152025-08-20T02:02:54ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-06-011610.3389/fimmu.2025.15890831589083In silico multi-epitope-based vaccine design for Mycobacterium avium complex speciesLeah Kashiri0Wonderful T. Choga1Wonderful T. Choga2Wonderful T. Choga3Tinashe Musasa4Pasipanodya Nziramasanga5Rutendo B. Gutsire6Lynn S. Zijenah7Norman L. Mukarati8Simani Gaseitsiwe9Simani Gaseitsiwe10Sikhulile Moyo11Sikhulile Moyo12Sikhulile Moyo13Sikhulile Moyo14Nyasha Chin’ombe15Medical Microbiology Unit, Department of Laboratory Diagnostic and Investigative Sciences, Faculty of Medicine and Health Sciences, University of Zimbabwe, Harare, ZimbabweDepartment of Medical Sciences, Botswana Harvard Health Partnership, Gaborone, BotswanaSchool of Allied Health Sciences, Faculty of Health Sciences, Gaborone, BotswanaDepartment of Applied Biology and Biochemistry, National University of Science and Technology, Bulawayo, ZimbabweMedical Microbiology Unit, Department of Laboratory Diagnostic and Investigative Sciences, Faculty of Medicine and Health Sciences, University of Zimbabwe, Harare, ZimbabweMedical Microbiology Unit, Department of Laboratory Diagnostic and Investigative Sciences, Faculty of Medicine and Health Sciences, University of Zimbabwe, Harare, ZimbabweImmunology Unit, Department of Laboratory Diagnostic and Investigative Sciences, Faculty of Medicine and Health Sciences, University of Zimbabwe, Harare, ZimbabweImmunology Unit, Department of Laboratory Diagnostic and Investigative Sciences, Faculty of Medicine and Health Sciences, University of Zimbabwe, Harare, ZimbabweDepartment of Clinical Veterinary Sciences, Faculty of Veterinary Sciences, University of Zimbabwe, Harare, ZimbabweDepartment of Medical Sciences, Botswana Harvard Health Partnership, Gaborone, BotswanaDepartment of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, United StatesDepartment of Medical Sciences, Botswana Harvard Health Partnership, Gaborone, BotswanaDepartment of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, United StatesSchool of Health Systems and Public Health, University of Pretoria, Pretoria, South AfricaDivision of Medical Virology, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, South AfricaMedical Microbiology Unit, Department of Laboratory Diagnostic and Investigative Sciences, Faculty of Medicine and Health Sciences, University of Zimbabwe, Harare, ZimbabweIntroductionThe Mycobacterium avium complex (MAC)—comprising M. colombiense, M. avium, andM. intracellulare—is an emerging group of opportunistic pathogens responsible for significant morbidity and mortality, particularly in immunocompromised individuals. Despite this growing burden, no vaccines currently provide cross-species protection. In silico vaccine design offers a rapid, cost-effective strategy to identify immunogenic epitopes and assemble multi-epitope constructs with optimized safety and efficacy. Accordingly, we aimed to develop a candidate multi-epitope vaccine (MEV) targeting conserved antigens across multiple MAC species.MethodsFrom a genomic survey of nontuberculous mycobacteria (NTM) in Zimbabwe, we assembled complete genomes for M. colombiense (MCOL), M. avium (MAV), and M. intracellulare (MINT). Using both local and global reference datasets, we screened the conserved immunodominant proteins 85A, 85B, and 85C for high-affinity T-helper lymphocyte (THL) epitopes. Promising epitopes were further evaluated for antigenicity, immunogenicity, physicochemical stability, and population coverage.ResultsEpitope mapping across the nine target proteins yielded 82 THL epitopes predicted to bind 13 MHC class II (DRB*) alleles, ensuring broad coverage within Zimbabwean and pan-African populations. Clustering analyses consolidated 26 unique epitopes into 11 consensus peptides, 65.4% of which derived from the 85B proteins. In silico immune simulations predicted robust humoral and cellular responses, including elevated IgG titers, T-helper and T-cytotoxic cell proliferation and increased secretion of IFN-γ and IL-2 following MEV administration.ConclusionThese findings indicate that our construct possesses strong immunogenic potential and cross-species applicability. We present here a rationally designed MEV candidate that merits further experimental validation as a broad-spectrum vaccine against multiple MAC species.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1589083/fullEpitopesMycobacterium avium complexVaccineAntigen85mycolyltransferaseTh1 helper T-cell |
| spellingShingle | Leah Kashiri Wonderful T. Choga Wonderful T. Choga Wonderful T. Choga Tinashe Musasa Pasipanodya Nziramasanga Rutendo B. Gutsire Lynn S. Zijenah Norman L. Mukarati Simani Gaseitsiwe Simani Gaseitsiwe Sikhulile Moyo Sikhulile Moyo Sikhulile Moyo Sikhulile Moyo Nyasha Chin’ombe In silico multi-epitope-based vaccine design for Mycobacterium avium complex species Frontiers in Immunology Epitopes Mycobacterium avium complex Vaccine Antigen85 mycolyltransferase Th1 helper T-cell |
| title | In silico multi-epitope-based vaccine design for Mycobacterium avium complex species |
| title_full | In silico multi-epitope-based vaccine design for Mycobacterium avium complex species |
| title_fullStr | In silico multi-epitope-based vaccine design for Mycobacterium avium complex species |
| title_full_unstemmed | In silico multi-epitope-based vaccine design for Mycobacterium avium complex species |
| title_short | In silico multi-epitope-based vaccine design for Mycobacterium avium complex species |
| title_sort | in silico multi epitope based vaccine design for mycobacterium avium complex species |
| topic | Epitopes Mycobacterium avium complex Vaccine Antigen85 mycolyltransferase Th1 helper T-cell |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1589083/full |
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