Live attenuated Mycobacterium bovis strains combined with the encapsulated H65 antigen as a vaccine strategy against bovine tuberculosis in a mouse model

Autores
Onnainty, Renée; Marini, María Rocío; Gravisaco, María José; Garcia, Elizabeth Andrea; Aagaard, Claus; Canal, Ana María; Granero, Gladys; Bigi, Fabiana; Blanco, Federico Carlos
Año de publicación
2024
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Mycobacterium bovis is an etiological agent of bovine tuberculosis (bTB) that also infects other mammals, including humans. The lack of an effective vaccine for the control of bTB highlights the need for developing new vaccines. In this study, we developed and evaluated an M. bovis strain deleted in the virulence genes phoP, esxA and esxB as a vaccine candidate against bTB in BALBc mice. The evaluated strains were the new live vaccine and BCG, alone or in combination with ncH65vD. The immunogen ncH65vD is a fusion protein H65, encapsulated together with vitamin D3, within the oily body of a nanocapsule composed of an antigen-loading polymeric shell. All vaccines conferred protection against the M. bovis challenge. However, no significant differences were detected among the vaccinated groups regarding bacterial loads in lungs and spleen. Mice vaccinated with the mutant strain plus ncH65vD showed negative Ziehl Neelsen staining of mycobacteria in their lungs, which suggests better control of bacteria replication according to this protection parameter. Consistently, this vaccination scheme showed the highest proportion of CD4 + T cells expressing the protection markers PD-1 and CXCR3 among the vaccinated groups. Correlation studies showed that PD-1 and CXCR3 expression levels in lung-resident CD4 T cells negatively correlated with the number of colony forming units of M. bovis in the lungs of mice. Therefore, the results suggest a link between the presence of PD-1 + and CXCR3 + cells at the site of the immune response against mycobacteria and the level of mycobacterial loads.
Instituto de Biotecnología
Fil: Onnainty, Renée. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Ciencias Farmacéuticas. Unidad de Investigaciones y Desarrollo en Tecnología Farmacéutica (UNITEFA); Argentina
Fil: Onnainty, Renée. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Marini, M. Rocío. Universidad Nacional del Litoral. Facultad de Ciencias Veterinarias. Departamento de Patología Básica; Argentina
Fil: Gravisaco, María José. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular (IABIMO); Argentina
Fil: Gravisaco, María José. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Garcia, Elizabeth Andrea. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular (IABIMO); Argentina
Fil: Garcia, Elizabeth Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Aagaard, Claus. Statens Serum Institut. Department of Infectious Disease Immunology; Dinamarca
Fil: Canal, Ana María. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Ciencias Farmacéuticas. Unidad de Investigaciones y Desarrollo en Tecnología Farmacéutica (UNITEFA); Argentina
Fil: Granero, Gladys. Universidad Nacional del Litoral. Facultad de Ciencias Veterinarias. Departamento de Patología Básica; Argentina
Fil: Bigi, Fabiana. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular (IABIMO); Argentina
Fil: Bigi, Fabiana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Blanco, Federico Carlos. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular (IABIMO); Argentina
Fil: Blanco, Federico Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fuente
Veterinary Microbiology 291 : 110007 (April 2024)
Materia
Mycobacterium bovis
Bovine Tuberculosis
Immune Response
Nanobiotechnology
Live Vaccines
Antigens
Tuberculosis Bovina
Respuesta Inmunológica
Nanobiotecnología
Vacuna Viva
Antígeno
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
oai:localhost:20.500.12123/18425
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spelling Live attenuated Mycobacterium bovis strains combined with the encapsulated H65 antigen as a vaccine strategy against bovine tuberculosis in a mouse modelOnnainty, RenéeMarini, María RocíoGravisaco, María JoséGarcia, Elizabeth AndreaAagaard, ClausCanal, Ana MaríaGranero, GladysBigi, FabianaBlanco, Federico CarlosMycobacterium bovisBovine TuberculosisImmune ResponseNanobiotechnologyLive VaccinesAntigensTuberculosis BovinaRespuesta InmunológicaNanobiotecnologíaVacuna VivaAntígenoMycobacterium bovis is an etiological agent of bovine tuberculosis (bTB) that also infects other mammals, including humans. The lack of an effective vaccine for the control of bTB highlights the need for developing new vaccines. In this study, we developed and evaluated an M. bovis strain deleted in the virulence genes phoP, esxA and esxB as a vaccine candidate against bTB in BALBc mice. The evaluated strains were the new live vaccine and BCG, alone or in combination with ncH65vD. The immunogen ncH65vD is a fusion protein H65, encapsulated together with vitamin D3, within the oily body of a nanocapsule composed of an antigen-loading polymeric shell. All vaccines conferred protection against the M. bovis challenge. However, no significant differences were detected among the vaccinated groups regarding bacterial loads in lungs and spleen. Mice vaccinated with the mutant strain plus ncH65vD showed negative Ziehl Neelsen staining of mycobacteria in their lungs, which suggests better control of bacteria replication according to this protection parameter. Consistently, this vaccination scheme showed the highest proportion of CD4 + T cells expressing the protection markers PD-1 and CXCR3 among the vaccinated groups. Correlation studies showed that PD-1 and CXCR3 expression levels in lung-resident CD4 T cells negatively correlated with the number of colony forming units of M. bovis in the lungs of mice. Therefore, the results suggest a link between the presence of PD-1 + and CXCR3 + cells at the site of the immune response against mycobacteria and the level of mycobacterial loads.Instituto de BiotecnologíaFil: Onnainty, Renée. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Ciencias Farmacéuticas. Unidad de Investigaciones y Desarrollo en Tecnología Farmacéutica (UNITEFA); ArgentinaFil: Onnainty, Renée. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Marini, M. Rocío. Universidad Nacional del Litoral. Facultad de Ciencias Veterinarias. Departamento de Patología Básica; ArgentinaFil: Gravisaco, María José. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular (IABIMO); ArgentinaFil: Gravisaco, María José. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Garcia, Elizabeth Andrea. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular (IABIMO); ArgentinaFil: Garcia, Elizabeth Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Aagaard, Claus. Statens Serum Institut. Department of Infectious Disease Immunology; DinamarcaFil: Canal, Ana María. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Ciencias Farmacéuticas. Unidad de Investigaciones y Desarrollo en Tecnología Farmacéutica (UNITEFA); ArgentinaFil: Granero, Gladys. Universidad Nacional del Litoral. Facultad de Ciencias Veterinarias. Departamento de Patología Básica; ArgentinaFil: Bigi, Fabiana. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular (IABIMO); ArgentinaFil: Bigi, Fabiana. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Blanco, Federico Carlos. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular (IABIMO); ArgentinaFil: Blanco, Federico Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaElsevier2024-07-08T13:55:41Z2024-07-08T13:55:41Z2024-04info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfhttp://hdl.handle.net/20.500.12123/18425https://www.sciencedirect.com/science/article/abs/pii/S03781135240002940378-1135https://doi.org/10.1016/j.vetmic.2024.110007Veterinary Microbiology 291 : 110007 (April 2024)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)2025-09-04T09:50:29Zoai:localhost:20.500.12123/18425instacron:INTAInstitucionalhttp://repositorio.inta.gob.ar/Organismo científico-tecnológicoNo correspondehttp://repositorio.inta.gob.ar/oai/requesttripaldi.nicolas@inta.gob.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:l2025-09-04 09:50:30.045INTA Digital (INTA) - Instituto Nacional de Tecnología Agropecuariafalse
dc.title.none.fl_str_mv Live attenuated Mycobacterium bovis strains combined with the encapsulated H65 antigen as a vaccine strategy against bovine tuberculosis in a mouse model
title Live attenuated Mycobacterium bovis strains combined with the encapsulated H65 antigen as a vaccine strategy against bovine tuberculosis in a mouse model
spellingShingle Live attenuated Mycobacterium bovis strains combined with the encapsulated H65 antigen as a vaccine strategy against bovine tuberculosis in a mouse model
Onnainty, Renée
Mycobacterium bovis
Bovine Tuberculosis
Immune Response
Nanobiotechnology
Live Vaccines
Antigens
Tuberculosis Bovina
Respuesta Inmunológica
Nanobiotecnología
Vacuna Viva
Antígeno
title_short Live attenuated Mycobacterium bovis strains combined with the encapsulated H65 antigen as a vaccine strategy against bovine tuberculosis in a mouse model
title_full Live attenuated Mycobacterium bovis strains combined with the encapsulated H65 antigen as a vaccine strategy against bovine tuberculosis in a mouse model
title_fullStr Live attenuated Mycobacterium bovis strains combined with the encapsulated H65 antigen as a vaccine strategy against bovine tuberculosis in a mouse model
title_full_unstemmed Live attenuated Mycobacterium bovis strains combined with the encapsulated H65 antigen as a vaccine strategy against bovine tuberculosis in a mouse model
title_sort Live attenuated Mycobacterium bovis strains combined with the encapsulated H65 antigen as a vaccine strategy against bovine tuberculosis in a mouse model
dc.creator.none.fl_str_mv Onnainty, Renée
Marini, María Rocío
Gravisaco, María José
Garcia, Elizabeth Andrea
Aagaard, Claus
Canal, Ana María
Granero, Gladys
Bigi, Fabiana
Blanco, Federico Carlos
author Onnainty, Renée
author_facet Onnainty, Renée
Marini, María Rocío
Gravisaco, María José
Garcia, Elizabeth Andrea
Aagaard, Claus
Canal, Ana María
Granero, Gladys
Bigi, Fabiana
Blanco, Federico Carlos
author_role author
author2 Marini, María Rocío
Gravisaco, María José
Garcia, Elizabeth Andrea
Aagaard, Claus
Canal, Ana María
Granero, Gladys
Bigi, Fabiana
Blanco, Federico Carlos
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Mycobacterium bovis
Bovine Tuberculosis
Immune Response
Nanobiotechnology
Live Vaccines
Antigens
Tuberculosis Bovina
Respuesta Inmunológica
Nanobiotecnología
Vacuna Viva
Antígeno
topic Mycobacterium bovis
Bovine Tuberculosis
Immune Response
Nanobiotechnology
Live Vaccines
Antigens
Tuberculosis Bovina
Respuesta Inmunológica
Nanobiotecnología
Vacuna Viva
Antígeno
dc.description.none.fl_txt_mv Mycobacterium bovis is an etiological agent of bovine tuberculosis (bTB) that also infects other mammals, including humans. The lack of an effective vaccine for the control of bTB highlights the need for developing new vaccines. In this study, we developed and evaluated an M. bovis strain deleted in the virulence genes phoP, esxA and esxB as a vaccine candidate against bTB in BALBc mice. The evaluated strains were the new live vaccine and BCG, alone or in combination with ncH65vD. The immunogen ncH65vD is a fusion protein H65, encapsulated together with vitamin D3, within the oily body of a nanocapsule composed of an antigen-loading polymeric shell. All vaccines conferred protection against the M. bovis challenge. However, no significant differences were detected among the vaccinated groups regarding bacterial loads in lungs and spleen. Mice vaccinated with the mutant strain plus ncH65vD showed negative Ziehl Neelsen staining of mycobacteria in their lungs, which suggests better control of bacteria replication according to this protection parameter. Consistently, this vaccination scheme showed the highest proportion of CD4 + T cells expressing the protection markers PD-1 and CXCR3 among the vaccinated groups. Correlation studies showed that PD-1 and CXCR3 expression levels in lung-resident CD4 T cells negatively correlated with the number of colony forming units of M. bovis in the lungs of mice. Therefore, the results suggest a link between the presence of PD-1 + and CXCR3 + cells at the site of the immune response against mycobacteria and the level of mycobacterial loads.
Instituto de Biotecnología
Fil: Onnainty, Renée. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Ciencias Farmacéuticas. Unidad de Investigaciones y Desarrollo en Tecnología Farmacéutica (UNITEFA); Argentina
Fil: Onnainty, Renée. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Marini, M. Rocío. Universidad Nacional del Litoral. Facultad de Ciencias Veterinarias. Departamento de Patología Básica; Argentina
Fil: Gravisaco, María José. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular (IABIMO); Argentina
Fil: Gravisaco, María José. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Garcia, Elizabeth Andrea. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular (IABIMO); Argentina
Fil: Garcia, Elizabeth Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Aagaard, Claus. Statens Serum Institut. Department of Infectious Disease Immunology; Dinamarca
Fil: Canal, Ana María. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Ciencias Farmacéuticas. Unidad de Investigaciones y Desarrollo en Tecnología Farmacéutica (UNITEFA); Argentina
Fil: Granero, Gladys. Universidad Nacional del Litoral. Facultad de Ciencias Veterinarias. Departamento de Patología Básica; Argentina
Fil: Bigi, Fabiana. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular (IABIMO); Argentina
Fil: Bigi, Fabiana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Blanco, Federico Carlos. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular (IABIMO); Argentina
Fil: Blanco, Federico Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
description Mycobacterium bovis is an etiological agent of bovine tuberculosis (bTB) that also infects other mammals, including humans. The lack of an effective vaccine for the control of bTB highlights the need for developing new vaccines. In this study, we developed and evaluated an M. bovis strain deleted in the virulence genes phoP, esxA and esxB as a vaccine candidate against bTB in BALBc mice. The evaluated strains were the new live vaccine and BCG, alone or in combination with ncH65vD. The immunogen ncH65vD is a fusion protein H65, encapsulated together with vitamin D3, within the oily body of a nanocapsule composed of an antigen-loading polymeric shell. All vaccines conferred protection against the M. bovis challenge. However, no significant differences were detected among the vaccinated groups regarding bacterial loads in lungs and spleen. Mice vaccinated with the mutant strain plus ncH65vD showed negative Ziehl Neelsen staining of mycobacteria in their lungs, which suggests better control of bacteria replication according to this protection parameter. Consistently, this vaccination scheme showed the highest proportion of CD4 + T cells expressing the protection markers PD-1 and CXCR3 among the vaccinated groups. Correlation studies showed that PD-1 and CXCR3 expression levels in lung-resident CD4 T cells negatively correlated with the number of colony forming units of M. bovis in the lungs of mice. Therefore, the results suggest a link between the presence of PD-1 + and CXCR3 + cells at the site of the immune response against mycobacteria and the level of mycobacterial loads.
publishDate 2024
dc.date.none.fl_str_mv 2024-07-08T13:55:41Z
2024-07-08T13:55:41Z
2024-04
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/20.500.12123/18425
https://www.sciencedirect.com/science/article/abs/pii/S0378113524000294
0378-1135
https://doi.org/10.1016/j.vetmic.2024.110007
url http://hdl.handle.net/20.500.12123/18425
https://www.sciencedirect.com/science/article/abs/pii/S0378113524000294
https://doi.org/10.1016/j.vetmic.2024.110007
identifier_str_mv 0378-1135
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 291 : 110007 (April 2024)
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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