Long-term evaluation in BALBc mice of a triple mutant of Mycobacterium bovis and the Bacillus Calmette-Guérin as potential vaccines against bovine tuberculosis
There is currently no commercial vaccine available against bovine tuberculosis (bTB). Mycobacterium bovis is the primary causative agent of bTB and is closely related to Mycobacterium tuberculosis, the pathogen responsible for human TB. Despite their limitations, mouse models are invaluable in early...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | info:ar-repo/semantics/artículo |
| Language: | Inglés |
| Published: |
Elsevier
2025
|
| Subjects: | |
| Online Access: | http://hdl.handle.net/20.500.12123/21369 https://www.sciencedirect.com/science/article/abs/pii/S0378113525000069 https://doi.org/10.1016/j.vetmic.2025.110371 |
| _version_ | 1855038391110860800 |
|---|---|
| author | Blanco, Federico Carlos Marini, María Rocío Klepp, Laura Ines Vazquez, Cristina Lourdes Garcia, Elizabeth Andrea Bigi, María Mercedes Canal, Ana María Bigi, Fabiana |
| author_browse | Bigi, Fabiana Bigi, María Mercedes Blanco, Federico Carlos Canal, Ana María Garcia, Elizabeth Andrea Klepp, Laura Ines Marini, María Rocío Vazquez, Cristina Lourdes |
| author_facet | Blanco, Federico Carlos Marini, María Rocío Klepp, Laura Ines Vazquez, Cristina Lourdes Garcia, Elizabeth Andrea Bigi, María Mercedes Canal, Ana María Bigi, Fabiana |
| author_sort | Blanco, Federico Carlos |
| collection | INTA Digital |
| description | There is currently no commercial vaccine available against bovine tuberculosis (bTB). Mycobacterium bovis is the primary causative agent of bTB and is closely related to Mycobacterium tuberculosis, the pathogen responsible for human TB. Despite their limitations, mouse models are invaluable in early vaccine development due to their genetic diversity, cost-effectiveness, and the availability of research tools. Researchers have tested many TB vaccines in mice, although few specifically target bTB. In this study, we developed a mutant strain of M. bovis lacking the esxA, esxB genes and the virulence gene fbpA to evaluate its long-term protective efficacy in BALB/c mice. We also analysed local immune responses and compared the results with those of BCG vaccination. Both BCG and the triple mutant strain Mb303ΔesxABΔfbpA demonstrated protection in BALB/c mice against M. bovis challenge, as evidenced by reduced bacterial lung loads. A histopathological analysis revealed the absence of ZN+ bacteria in the lungs of M. bovis-challenged mice vaccinated with BCG. In addition, mice vaccinated with the triple mutant exhibited a higher profile of protective immune CD4 + T cells in the lungs than those vaccinated with BCG. Notably, there was a negative correlation between the bacterial loads in the lungs of mice and the T cell subpopulations CD4 +KLRG1-PD1 +CCR7 + and CD4 +KLRG1-CXCR3 + , indicating that these T cell phenotypes are potential markers of protection against bTB. These findings indicate that the Mb303ΔesxABΔfbpA strain provides long-term protection against bTB. Furthermore, the results reaffirm the potential of BCG as a vaccine against this disease. |
| format | info:ar-repo/semantics/artículo |
| id | INTA21369 |
| institution | Instituto Nacional de Tecnología Agropecuaria (INTA -Argentina) |
| language | Inglés |
| publishDate | 2025 |
| publishDateRange | 2025 |
| publishDateSort | 2025 |
| publisher | Elsevier |
| publisherStr | Elsevier |
| record_format | dspace |
| spelling | INTA213692025-02-20T14:16:00Z Long-term evaluation in BALBc mice of a triple mutant of Mycobacterium bovis and the Bacillus Calmette-Guérin as potential vaccines against bovine tuberculosis Blanco, Federico Carlos Marini, María Rocío Klepp, Laura Ines Vazquez, Cristina Lourdes Garcia, Elizabeth Andrea Bigi, María Mercedes Canal, Ana María Bigi, Fabiana Vacuna Enfermedades de los Animales Tuberculosis Bovina Ratón Vaccines Animal Diseases Mycobacterium bovis Bovine Tuberculosis Mice There is currently no commercial vaccine available against bovine tuberculosis (bTB). Mycobacterium bovis is the primary causative agent of bTB and is closely related to Mycobacterium tuberculosis, the pathogen responsible for human TB. Despite their limitations, mouse models are invaluable in early vaccine development due to their genetic diversity, cost-effectiveness, and the availability of research tools. Researchers have tested many TB vaccines in mice, although few specifically target bTB. In this study, we developed a mutant strain of M. bovis lacking the esxA, esxB genes and the virulence gene fbpA to evaluate its long-term protective efficacy in BALB/c mice. We also analysed local immune responses and compared the results with those of BCG vaccination. Both BCG and the triple mutant strain Mb303ΔesxABΔfbpA demonstrated protection in BALB/c mice against M. bovis challenge, as evidenced by reduced bacterial lung loads. A histopathological analysis revealed the absence of ZN+ bacteria in the lungs of M. bovis-challenged mice vaccinated with BCG. In addition, mice vaccinated with the triple mutant exhibited a higher profile of protective immune CD4 + T cells in the lungs than those vaccinated with BCG. Notably, there was a negative correlation between the bacterial loads in the lungs of mice and the T cell subpopulations CD4 +KLRG1-PD1 +CCR7 + and CD4 +KLRG1-CXCR3 + , indicating that these T cell phenotypes are potential markers of protection against bTB. These findings indicate that the Mb303ΔesxABΔfbpA strain provides long-term protection against bTB. Furthermore, the results reaffirm the potential of BCG as a vaccine against this disease. Instituto de Biotecnología Fil: Blanco, Federico Carlos. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; Argentina Fil: Blanco, Federico Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Marini, M. Rocío. Universidad Nacional del Litoral. Facultad de Ciencias Veterinarias. Laboratorio de Anatomía Patológica; Argentina Fil: Klepp, Laura Ines. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; Argentina Fil: Klepp, Laura Ines. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Vazquez, Cristina Lourdes. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; Argentina Fil: Vazquez, Cristina Lourdes. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Garcia, Elizabeth Andrea. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; Argentina Fil: Garcia, Elizabeth Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Bigi, María Mercedes. Universidad de Buenos Aires. Facultad de Medicina; Argentina Fil: Canal, Ana María. Universidad Nacional del Litoral. Facultad de Ciencias Veterinarias. Laboratorio de Anatomía Patológica; Argentina Fil: Bigi, Fabiana. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; Argentina Fil: Bigi, Fabiana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina 2025-02-20T12:27:58Z 2025-02-20T12:27:58Z 2025-03 info:ar-repo/semantics/artículo info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://hdl.handle.net/20.500.12123/21369 https://www.sciencedirect.com/science/article/abs/pii/S0378113525000069 0378-1135 1873-2542 https://doi.org/10.1016/j.vetmic.2025.110371 eng info:eu-repograntAgreement/INTA/2023-PD-L06-I116, Implementación de tecnologías y nuevas estrategias preventivas y terapéuticas para el desarrollo sustentable y eficiente de la producción animal en el marco de Una Salud info:eu-repo/semantics/restrictedAccess http://creativecommons.org/licenses/by-nc-sa/4.0/ Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) application/pdf Elsevier Veterinary Microbiology 302 : 110371. (March 2025) |
| spellingShingle | Vacuna Enfermedades de los Animales Tuberculosis Bovina Ratón Vaccines Animal Diseases Mycobacterium bovis Bovine Tuberculosis Mice Blanco, Federico Carlos Marini, María Rocío Klepp, Laura Ines Vazquez, Cristina Lourdes Garcia, Elizabeth Andrea Bigi, María Mercedes Canal, Ana María Bigi, Fabiana Long-term evaluation in BALBc mice of a triple mutant of Mycobacterium bovis and the Bacillus Calmette-Guérin as potential vaccines against bovine tuberculosis |
| title | Long-term evaluation in BALBc mice of a triple mutant of Mycobacterium bovis and the Bacillus Calmette-Guérin as potential vaccines against bovine tuberculosis |
| title_full | Long-term evaluation in BALBc mice of a triple mutant of Mycobacterium bovis and the Bacillus Calmette-Guérin as potential vaccines against bovine tuberculosis |
| title_fullStr | Long-term evaluation in BALBc mice of a triple mutant of Mycobacterium bovis and the Bacillus Calmette-Guérin as potential vaccines against bovine tuberculosis |
| title_full_unstemmed | Long-term evaluation in BALBc mice of a triple mutant of Mycobacterium bovis and the Bacillus Calmette-Guérin as potential vaccines against bovine tuberculosis |
| title_short | Long-term evaluation in BALBc mice of a triple mutant of Mycobacterium bovis and the Bacillus Calmette-Guérin as potential vaccines against bovine tuberculosis |
| title_sort | long term evaluation in balbc mice of a triple mutant of mycobacterium bovis and the bacillus calmette guerin as potential vaccines against bovine tuberculosis |
| topic | Vacuna Enfermedades de los Animales Tuberculosis Bovina Ratón Vaccines Animal Diseases Mycobacterium bovis Bovine Tuberculosis Mice |
| url | http://hdl.handle.net/20.500.12123/21369 https://www.sciencedirect.com/science/article/abs/pii/S0378113525000069 https://doi.org/10.1016/j.vetmic.2025.110371 |
| work_keys_str_mv | AT blancofedericocarlos longtermevaluationinbalbcmiceofatriplemutantofmycobacteriumbovisandthebacilluscalmetteguerinaspotentialvaccinesagainstbovinetuberculosis AT marinimariarocio longtermevaluationinbalbcmiceofatriplemutantofmycobacteriumbovisandthebacilluscalmetteguerinaspotentialvaccinesagainstbovinetuberculosis AT klepplauraines longtermevaluationinbalbcmiceofatriplemutantofmycobacteriumbovisandthebacilluscalmetteguerinaspotentialvaccinesagainstbovinetuberculosis AT vazquezcristinalourdes longtermevaluationinbalbcmiceofatriplemutantofmycobacteriumbovisandthebacilluscalmetteguerinaspotentialvaccinesagainstbovinetuberculosis AT garciaelizabethandrea longtermevaluationinbalbcmiceofatriplemutantofmycobacteriumbovisandthebacilluscalmetteguerinaspotentialvaccinesagainstbovinetuberculosis AT bigimariamercedes longtermevaluationinbalbcmiceofatriplemutantofmycobacteriumbovisandthebacilluscalmetteguerinaspotentialvaccinesagainstbovinetuberculosis AT canalanamaria longtermevaluationinbalbcmiceofatriplemutantofmycobacteriumbovisandthebacilluscalmetteguerinaspotentialvaccinesagainstbovinetuberculosis AT bigifabiana longtermevaluationinbalbcmiceofatriplemutantofmycobacteriumbovisandthebacilluscalmetteguerinaspotentialvaccinesagainstbovinetuberculosis |