M72 Fusion proteins in nanocapsules enhance BCG efficacy against bovine tuberculosis in a mouse model

Autores
Blanco, Federico Carlos; Onnainty, Renée; Marini, María Rocío; Klepp, Laura Ines; Garcia, Elizabeth Andrea; Vazquez, Cristina Lourdes; Canal, Ana María; Granero, Gladys; Bigi, Fabiana
Año de publicación
2025
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Mycobacterium bovis is the causative pathogen of bovine tuberculosis (bTB), a disease that affects cattle and other mammals, including humans. Currently, there is no efficient vaccine against bTB, underscoring the need for novel immunization strategies. The M72 fusion protein, composed of three polypeptides derived from Mycobacterium tuberculosis and M. bovis, has demonstrated protective efficacy against M. tuberculosis in clinical trials when combined with the AS01E adjuvant. Given the established efficacy of nanocapsule formulations as vaccine delivery systems, this study evaluated a novel immunization strategy combining BCG with either full-length M72 or a truncated M72 fused to a streptococcal albumin-binding domain (ABDsM72). Both antigens were encapsulated in chitosan/alginate nanocapsules and assessed in a murine M. bovis challenge model. Priming with BCG followed by an M72 boost significantly improved splenic protection compared to BCG alone, but it did not enhance pulmonary protection. Notably, boosting with ABDsM72 further increased the proportion of CD4+KLRG1-CXCR3+ T cells in the lungs of M. bovis-challenged mice, a key correlate of protective immunity. These findings demonstrate that chitosan/alginate-encapsulated antigens enhance BCG-induced immunity, supporting their potential as next-generation vaccine candidates for bTB control.
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: 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. 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: 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: 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: Canal, Ana María. Universidad Nacional del Litoral. Facultad de Ciencias Veterinarias. Laboratorio de Anatomía Patológica; Argentina
Fil: Granero, Gladys. 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. Consejo Nacional de Investigaciones Científicas y Técnicas; 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
Pathogens 14 (6) : 592 (June 2025)
Materia
Mycobacterium bovis
Mice
Vaccines
Chitosan
Bovine Tuberculosis
Nanocapsules
Ratón
Vacuna
Quitosano
Tuberculosis Bovina
Nanocápsula
Nivel de accesibilidad
acceso abierto
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:20.500.12123/22703
Acceder
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oai_identifier_str oai:localhost:20.500.12123/22703
network_acronym_str INTADig
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network_name_str INTA Digital (INTA)
spelling M72 Fusion proteins in nanocapsules enhance BCG efficacy against bovine tuberculosis in a mouse modelBlanco, Federico CarlosOnnainty, RenéeMarini, María RocíoKlepp, Laura InesGarcia, Elizabeth AndreaVazquez, Cristina LourdesCanal, Ana MaríaGranero, GladysBigi, FabianaMycobacterium bovisMiceVaccinesChitosanBovine TuberculosisNanocapsulesRatónVacunaQuitosanoTuberculosis BovinaNanocápsulaMycobacterium bovis is the causative pathogen of bovine tuberculosis (bTB), a disease that affects cattle and other mammals, including humans. Currently, there is no efficient vaccine against bTB, underscoring the need for novel immunization strategies. The M72 fusion protein, composed of three polypeptides derived from Mycobacterium tuberculosis and M. bovis, has demonstrated protective efficacy against M. tuberculosis in clinical trials when combined with the AS01E adjuvant. Given the established efficacy of nanocapsule formulations as vaccine delivery systems, this study evaluated a novel immunization strategy combining BCG with either full-length M72 or a truncated M72 fused to a streptococcal albumin-binding domain (ABDsM72). Both antigens were encapsulated in chitosan/alginate nanocapsules and assessed in a murine M. bovis challenge model. Priming with BCG followed by an M72 boost significantly improved splenic protection compared to BCG alone, but it did not enhance pulmonary protection. Notably, boosting with ABDsM72 further increased the proportion of CD4+KLRG1-CXCR3+ T cells in the lungs of M. bovis-challenged mice, a key correlate of protective immunity. These findings demonstrate that chitosan/alginate-encapsulated antigens enhance BCG-induced immunity, supporting their potential as next-generation vaccine candidates for bTB control.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: 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. 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: 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: 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: Canal, Ana María. Universidad Nacional del Litoral. Facultad de Ciencias Veterinarias. Laboratorio de Anatomía Patológica; ArgentinaFil: Granero, Gladys. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Ciencias Farmacéuticas. Unidad de Investigaciones y Desarrollo en Tecnología Farmacéutica (UNITEFA); ArgentinaFil: Granero, Gladys. Consejo Nacional de Investigaciones Científicas y Técnicas; 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; ArgentinaMDPI2025-06-17T14:10:38Z2025-06-17T14:10:38Z2025-06info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfhttp://hdl.handle.net/20.500.12123/22703https://www.mdpi.com/2076-0817/14/6/5922076-0817https://doi.org/10.3390/pathogens14060592Pathogens 14 (6) : 592 (June 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/openAccesshttp://creativecommons.org/licenses/by-nc-sa/4.0/Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)2025-09-29T13:47:21Zoai:localhost:20.500.12123/22703instacron: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 13:47:22.322INTA Digital (INTA) - Instituto Nacional de Tecnología Agropecuariafalse
dc.title.none.fl_str_mv M72 Fusion proteins in nanocapsules enhance BCG efficacy against bovine tuberculosis in a mouse model
title M72 Fusion proteins in nanocapsules enhance BCG efficacy against bovine tuberculosis in a mouse model
spellingShingle M72 Fusion proteins in nanocapsules enhance BCG efficacy against bovine tuberculosis in a mouse model
Blanco, Federico Carlos
Mycobacterium bovis
Mice
Vaccines
Chitosan
Bovine Tuberculosis
Nanocapsules
Ratón
Vacuna
Quitosano
Tuberculosis Bovina
Nanocápsula
title_short M72 Fusion proteins in nanocapsules enhance BCG efficacy against bovine tuberculosis in a mouse model
title_full M72 Fusion proteins in nanocapsules enhance BCG efficacy against bovine tuberculosis in a mouse model
title_fullStr M72 Fusion proteins in nanocapsules enhance BCG efficacy against bovine tuberculosis in a mouse model
title_full_unstemmed M72 Fusion proteins in nanocapsules enhance BCG efficacy against bovine tuberculosis in a mouse model
title_sort M72 Fusion proteins in nanocapsules enhance BCG efficacy against bovine tuberculosis in a mouse model
dc.creator.none.fl_str_mv Blanco, Federico Carlos
Onnainty, Renée
Marini, María Rocío
Klepp, Laura Ines
Garcia, Elizabeth Andrea
Vazquez, Cristina Lourdes
Canal, Ana María
Granero, Gladys
Bigi, Fabiana
author Blanco, Federico Carlos
author_facet Blanco, Federico Carlos
Onnainty, Renée
Marini, María Rocío
Klepp, Laura Ines
Garcia, Elizabeth Andrea
Vazquez, Cristina Lourdes
Canal, Ana María
Granero, Gladys
Bigi, Fabiana
author_role author
author2 Onnainty, Renée
Marini, María Rocío
Klepp, Laura Ines
Garcia, Elizabeth Andrea
Vazquez, Cristina Lourdes
Canal, Ana María
Granero, Gladys
Bigi, Fabiana
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Mycobacterium bovis
Mice
Vaccines
Chitosan
Bovine Tuberculosis
Nanocapsules
Ratón
Vacuna
Quitosano
Tuberculosis Bovina
Nanocápsula
topic Mycobacterium bovis
Mice
Vaccines
Chitosan
Bovine Tuberculosis
Nanocapsules
Ratón
Vacuna
Quitosano
Tuberculosis Bovina
Nanocápsula
dc.description.none.fl_txt_mv Mycobacterium bovis is the causative pathogen of bovine tuberculosis (bTB), a disease that affects cattle and other mammals, including humans. Currently, there is no efficient vaccine against bTB, underscoring the need for novel immunization strategies. The M72 fusion protein, composed of three polypeptides derived from Mycobacterium tuberculosis and M. bovis, has demonstrated protective efficacy against M. tuberculosis in clinical trials when combined with the AS01E adjuvant. Given the established efficacy of nanocapsule formulations as vaccine delivery systems, this study evaluated a novel immunization strategy combining BCG with either full-length M72 or a truncated M72 fused to a streptococcal albumin-binding domain (ABDsM72). Both antigens were encapsulated in chitosan/alginate nanocapsules and assessed in a murine M. bovis challenge model. Priming with BCG followed by an M72 boost significantly improved splenic protection compared to BCG alone, but it did not enhance pulmonary protection. Notably, boosting with ABDsM72 further increased the proportion of CD4+KLRG1-CXCR3+ T cells in the lungs of M. bovis-challenged mice, a key correlate of protective immunity. These findings demonstrate that chitosan/alginate-encapsulated antigens enhance BCG-induced immunity, supporting their potential as next-generation vaccine candidates for bTB control.
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: 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. 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: 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: 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: Canal, Ana María. Universidad Nacional del Litoral. Facultad de Ciencias Veterinarias. Laboratorio de Anatomía Patológica; Argentina
Fil: Granero, Gladys. 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. Consejo Nacional de Investigaciones Científicas y Técnicas; 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 Mycobacterium bovis is the causative pathogen of bovine tuberculosis (bTB), a disease that affects cattle and other mammals, including humans. Currently, there is no efficient vaccine against bTB, underscoring the need for novel immunization strategies. The M72 fusion protein, composed of three polypeptides derived from Mycobacterium tuberculosis and M. bovis, has demonstrated protective efficacy against M. tuberculosis in clinical trials when combined with the AS01E adjuvant. Given the established efficacy of nanocapsule formulations as vaccine delivery systems, this study evaluated a novel immunization strategy combining BCG with either full-length M72 or a truncated M72 fused to a streptococcal albumin-binding domain (ABDsM72). Both antigens were encapsulated in chitosan/alginate nanocapsules and assessed in a murine M. bovis challenge model. Priming with BCG followed by an M72 boost significantly improved splenic protection compared to BCG alone, but it did not enhance pulmonary protection. Notably, boosting with ABDsM72 further increased the proportion of CD4+KLRG1-CXCR3+ T cells in the lungs of M. bovis-challenged mice, a key correlate of protective immunity. These findings demonstrate that chitosan/alginate-encapsulated antigens enhance BCG-induced immunity, supporting their potential as next-generation vaccine candidates for bTB control.
publishDate 2025
dc.date.none.fl_str_mv 2025-06-17T14:10:38Z
2025-06-17T14:10:38Z
2025-06
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/20.500.12123/22703
https://www.mdpi.com/2076-0817/14/6/592
2076-0817
https://doi.org/10.3390/pathogens14060592
url http://hdl.handle.net/20.500.12123/22703
https://www.mdpi.com/2076-0817/14/6/592
https://doi.org/10.3390/pathogens14060592
identifier_str_mv 2076-0817
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/openAccess
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 openAccess
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 MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv Pathogens 14 (6) : 592 (June 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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