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

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 poly...

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Autores principales: Blanco, Federico Carlos, Onnainty, Renée, Marini, María Rocío, Klepp, Laura Ines, Garcia, Elizabeth Andrea, Vazquez, Cristina Lourdes, Canal, Ana María, Granero, Gladys, Bigi, Fabiana
Formato: Artículo
Lenguaje:Inglés
Publicado: MDPI 2025
Materias:
Acceso en línea:http://hdl.handle.net/20.500.12123/22703
https://www.mdpi.com/2076-0817/14/6/592
https://doi.org/10.3390/pathogens14060592
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author 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_browse Bigi, Fabiana
Blanco, Federico Carlos
Canal, Ana María
Garcia, Elizabeth Andrea
Granero, Gladys
Klepp, Laura Ines
Marini, María Rocío
Onnainty, Renée
Vazquez, Cristina Lourdes
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_sort Blanco, Federico Carlos
collection INTA Digital
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.
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spelling INTA227032025-06-17T14:36:32Z M72 Fusion proteins in nanocapsules enhance BCG efficacy against bovine tuberculosis in a mouse model Blanco, Federico Carlos Onnainty, Renée Marini, María Rocío Klepp, Laura Ines Garcia, Elizabeth Andrea Vazquez, Cristina Lourdes Canal, Ana María Granero, Gladys Bigi, Fabiana Mycobacterium bovis Mice Vaccines Chitosan Bovine Tuberculosis Nanocapsules Ratón Vacuna Quitosano Tuberculosis Bovina Nanocápsula 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 2025-06-17T14:10:38Z 2025-06-17T14:10:38Z 2025-06 info:ar-repo/semantics/artículo info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion 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 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/openAccess 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 MDPI Pathogens 14 (6) : 592 (June 2025)
spellingShingle Mycobacterium bovis
Mice
Vaccines
Chitosan
Bovine Tuberculosis
Nanocapsules
Ratón
Vacuna
Quitosano
Tuberculosis Bovina
Nanocápsula
Blanco, Federico Carlos
Onnainty, Renée
Marini, María Rocío
Klepp, Laura Ines
Garcia, Elizabeth Andrea
Vazquez, Cristina Lourdes
Canal, Ana María
Granero, Gladys
Bigi, Fabiana
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
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_short 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
topic Mycobacterium bovis
Mice
Vaccines
Chitosan
Bovine Tuberculosis
Nanocapsules
Ratón
Vacuna
Quitosano
Tuberculosis Bovina
Nanocápsula
url http://hdl.handle.net/20.500.12123/22703
https://www.mdpi.com/2076-0817/14/6/592
https://doi.org/10.3390/pathogens14060592
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