Long-term evaluation in BALBc mice of a triple mutant of Mycobacterium bovis and the Bacillus Calmette-Guérin as potential vaccines against bovine tuberculosis

Autores
Blanco, Federico Carlos; Marini, María Rocío; Klepp, Laura Ines; Vazquez, Cristina Lourdes; Garcia, Elizabeth Andrea; Bigi, María Mercedes; Canal, Ana María; Bigi, Fabiana
Año de publicación
2025
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
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
Fuente
Veterinary Microbiology 302 : 110371. (March 2025)
Materia
Vacuna
Enfermedades de los Animales
Tuberculosis Bovina
Ratón
Vaccines
Animal Diseases
Mycobacterium bovis
Bovine Tuberculosis
Mice
Nivel de accesibilidad
acceso restringido
Condiciones de uso
http://creativecommons.org/licenses/by-nc-sa/4.0/
Repositorio
INTA Digital (INTA)
Institución
Instituto Nacional de Tecnología Agropecuaria
OAI Identificador
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spelling Long-term evaluation in BALBc mice of a triple mutant of Mycobacterium bovis and the Bacillus Calmette-Guérin as potential vaccines against bovine tuberculosisBlanco, Federico CarlosMarini, María RocíoKlepp, Laura InesVazquez, Cristina LourdesGarcia, Elizabeth AndreaBigi, María MercedesCanal, Ana MaríaBigi, FabianaVacunaEnfermedades de los AnimalesTuberculosis BovinaRatónVaccinesAnimal DiseasesMycobacterium bovisBovine TuberculosisMiceThere 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 BiotecnologíaFil: Blanco, Federico Carlos. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; ArgentinaFil: Blanco, Federico Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Marini, M. Rocío. Universidad Nacional del Litoral. Facultad de Ciencias Veterinarias. Laboratorio de Anatomía Patológica; ArgentinaFil: Klepp, Laura Ines. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; ArgentinaFil: Klepp, Laura Ines. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Vazquez, Cristina Lourdes. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; ArgentinaFil: Vazquez, Cristina Lourdes. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Garcia, Elizabeth Andrea. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; ArgentinaFil: Garcia, Elizabeth Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bigi, María Mercedes. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Canal, Ana María. Universidad Nacional del Litoral. Facultad de Ciencias Veterinarias. Laboratorio de Anatomía Patológica; ArgentinaFil: Bigi, Fabiana. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; ArgentinaFil: Bigi, Fabiana. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaElsevier2025-02-20T12:27:58Z2025-02-20T12:27:58Z2025-03info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfhttp://hdl.handle.net/20.500.12123/21369https://www.sciencedirect.com/science/article/abs/pii/S03781135250000690378-11351873-2542https://doi.org/10.1016/j.vetmic.2025.110371Veterinary Microbiology 302 : 110371. (March 2025)reponame:INTA Digital (INTA)instname:Instituto Nacional de Tecnología Agropecuariaenginfo: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 Saludinfo:eu-repo/semantics/restrictedAccesshttp://creativecommons.org/licenses/by-nc-sa/4.0/Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)2025-09-29T13:47:09Zoai:localhost:20.500.12123/21369instacron:INTAInstitucionalhttp://repositorio.inta.gob.ar/Organismo científico-tecnológicoNo correspondehttp://repositorio.inta.gob.ar/oai/requesttripaldi.nicolas@inta.gob.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:l2025-09-29 13:47:09.52INTA Digital (INTA) - Instituto Nacional de Tecnología Agropecuariafalse
dc.title.none.fl_str_mv 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
spellingShingle 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
Vacuna
Enfermedades de los Animales
Tuberculosis Bovina
Ratón
Vaccines
Animal Diseases
Mycobacterium bovis
Bovine Tuberculosis
Mice
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_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_sort Long-term evaluation in BALBc mice of a triple mutant of Mycobacterium bovis and the Bacillus Calmette-Guérin as potential vaccines against bovine tuberculosis
dc.creator.none.fl_str_mv Blanco, Federico Carlos
Marini, María Rocío
Klepp, Laura Ines
Vazquez, Cristina Lourdes
Garcia, Elizabeth Andrea
Bigi, María Mercedes
Canal, Ana María
Bigi, Fabiana
author Blanco, Federico Carlos
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_role author
author2 Marini, María Rocío
Klepp, Laura Ines
Vazquez, Cristina Lourdes
Garcia, Elizabeth Andrea
Bigi, María Mercedes
Canal, Ana María
Bigi, Fabiana
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Vacuna
Enfermedades de los Animales
Tuberculosis Bovina
Ratón
Vaccines
Animal Diseases
Mycobacterium bovis
Bovine Tuberculosis
Mice
topic Vacuna
Enfermedades de los Animales
Tuberculosis Bovina
Ratón
Vaccines
Animal Diseases
Mycobacterium bovis
Bovine Tuberculosis
Mice
dc.description.none.fl_txt_mv 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
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.
publishDate 2025
dc.date.none.fl_str_mv 2025-02-20T12:27:58Z
2025-02-20T12:27:58Z
2025-03
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv 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
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
identifier_str_mv 0378-1135
1873-2542
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 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
dc.rights.none.fl_str_mv 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)
eu_rights_str_mv restrictedAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by-nc-sa/4.0/
Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv Veterinary Microbiology 302 : 110371. (March 2025)
reponame:INTA Digital (INTA)
instname:Instituto Nacional de Tecnología Agropecuaria
reponame_str INTA Digital (INTA)
collection INTA Digital (INTA)
instname_str Instituto Nacional de Tecnología Agropecuaria
repository.name.fl_str_mv INTA Digital (INTA) - Instituto Nacional de Tecnología Agropecuaria
repository.mail.fl_str_mv tripaldi.nicolas@inta.gob.ar
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