Live attenuated Mycobacterium bovis strains combined with the encapsulated H65 antigen as a vaccine strategy against bovine tuberculosis in a mouse model
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...
| Autores principales: | , , , , , , , , |
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| Formato: | Artículo |
| Lenguaje: | Inglés |
| Publicado: |
Elsevier
2024
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| Materias: | |
| Acceso en línea: | 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 |
| _version_ | 1855486170309328896 |
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| author | Onnainty, Renée Marini, María Rocío Gravisaco, María José Garcia, Elizabeth Andrea Aagaard, Claus Canal, Ana María Granero, Gladys Bigi, Fabiana Blanco, Federico Carlos |
| author_browse | Aagaard, Claus Bigi, Fabiana Blanco, Federico Carlos Canal, Ana María Garcia, Elizabeth Andrea Granero, Gladys Gravisaco, María José Marini, María Rocío 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_sort | Onnainty, Renée |
| collection | INTA Digital |
| 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. |
| format | Artículo |
| id | INTA18425 |
| institution | Instituto Nacional de Tecnología Agropecuaria (INTA -Argentina) |
| language | Inglés |
| publishDate | 2024 |
| publishDateRange | 2024 |
| publishDateSort | 2024 |
| publisher | Elsevier |
| publisherStr | Elsevier |
| record_format | dspace |
| spelling | INTA184252025-02-20T12:10:49Z Live attenuated Mycobacterium bovis strains combined with the encapsulated H65 antigen as a vaccine strategy against bovine tuberculosis in a mouse model Onnainty, Renée Marini, María Rocío Gravisaco, María José Garcia, Elizabeth Andrea Aagaard, Claus Canal, Ana María Granero, Gladys Bigi, Fabiana Blanco, Federico Carlos Mycobacterium bovis Bovine Tuberculosis Immune Response Nanobiotechnology Live Vaccines Antigens Tuberculosis Bovina Respuesta Inmunológica Nanobiotecnología Vacuna Viva Antígeno 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 2024-07-08T13:55:41Z 2024-07-08T13:55:41Z 2024-04 info:ar-repo/semantics/artículo info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion 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 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 291 : 110007 (April 2024) |
| spellingShingle | Mycobacterium bovis Bovine Tuberculosis Immune Response Nanobiotechnology Live Vaccines Antigens Tuberculosis Bovina Respuesta Inmunológica Nanobiotecnología Vacuna Viva Antígeno Onnainty, Renée Marini, María Rocío Gravisaco, María José Garcia, Elizabeth Andrea Aagaard, Claus Canal, Ana María Granero, Gladys Bigi, Fabiana Blanco, Federico Carlos 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 |
| 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_short | 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 |
| topic | Mycobacterium bovis Bovine Tuberculosis Immune Response Nanobiotechnology Live Vaccines Antigens Tuberculosis Bovina Respuesta Inmunológica Nanobiotecnología Vacuna Viva Antígeno |
| 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 |
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