Vaccination with BCGΔBCG1419c protects against pulmonary and extrapulmonary TB and is safer than BCG

Abstract A single intradermal vaccination with an antibiotic-less version of BCGΔBCG1419c given to guinea pigs conferred a significant improvement in outcome following a low dose aerosol exposure to M. tuberculosis compared to that provided by a single dose of BCG Pasteur. BCGΔBCG1419c was more atte...

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Autores principales:	Michel de Jesús Aceves-Sánchez, Mario Alberto Flores-Valdez, César Pedroza-Roldán, Elizabeth Creissen, Linda Izzo, Fabiola Silva-Angulo, Clinton Dawson, Angelo Izzo, Helle Bielefeldt-Ohmann, Cristian Alfredo Segura-Cerda, Wendy López-Romero, Jorge Bravo-Madrigal, Jorge Alberto Barrios-Payán, Miguel Ángel de la Cruz, Miguel Ares, María Guadalupe Jorge-Espinoza
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5c59aca1dc2a4630bd0accb20d8195d8
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spelling	oai:doaj.org-article:5c59aca1dc2a4630bd0accb20d8195d82021-12-02T17:41:06ZVaccination with BCGΔBCG1419c protects against pulmonary and extrapulmonary TB and is safer than BCG10.1038/s41598-021-91993-82045-2322https://doaj.org/article/5c59aca1dc2a4630bd0accb20d8195d82021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-91993-8https://doaj.org/toc/2045-2322Abstract A single intradermal vaccination with an antibiotic-less version of BCGΔBCG1419c given to guinea pigs conferred a significant improvement in outcome following a low dose aerosol exposure to M. tuberculosis compared to that provided by a single dose of BCG Pasteur. BCGΔBCG1419c was more attenuated than BCG in murine macrophages, athymic, BALB/c, and C57BL/6 mice. In guinea pigs, BCGΔBCG1419c was at least as attenuated as BCG and induced similar dermal reactivity to that of BCG. Vaccination of guinea pigs with BCGΔBCG1419c resulted in increased anti-PPD IgG compared with those receiving BCG. Guinea pigs vaccinated with BCGΔBCG1419c showed a significant reduction of M. tuberculosis replication in lungs and spleens compared with BCG, as well as a significant reduction of pulmonary and extrapulmonary tuberculosis (TB) pathology measured using pathology scores recorded at necropsy. Evaluation of cytokines produced in lungs of infected guinea pigs showed that BCGΔBCG1419c significantly reduced TNF-α and IL-17 compared with BCG-vaccinated animals, with no changes in IL-10. This work demonstrates a significantly improved protection against pulmonary and extrapulmonary TB provided by BCGΔBCG1419c in susceptible guinea pigs together with an increased safety compared with BCG in several models. These results support the continued development of BCGΔBCG1419c as an effective vaccine for TB.Michel de Jesús Aceves-SánchezMario Alberto Flores-ValdezCésar Pedroza-RoldánElizabeth CreissenLinda IzzoFabiola Silva-AnguloClinton DawsonAngelo IzzoHelle Bielefeldt-OhmannCristian Alfredo Segura-CerdaWendy López-RomeroJorge Bravo-MadrigalJorge Alberto Barrios-PayánMiguel Ángel de la CruzMiguel AresMaría Guadalupe Jorge-EspinozaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Michel de Jesús Aceves-Sánchez Mario Alberto Flores-Valdez César Pedroza-Roldán Elizabeth Creissen Linda Izzo Fabiola Silva-Angulo Clinton Dawson Angelo Izzo Helle Bielefeldt-Ohmann Cristian Alfredo Segura-Cerda Wendy López-Romero Jorge Bravo-Madrigal Jorge Alberto Barrios-Payán Miguel Ángel de la Cruz Miguel Ares María Guadalupe Jorge-Espinoza Vaccination with BCGΔBCG1419c protects against pulmonary and extrapulmonary TB and is safer than BCG
description	Abstract A single intradermal vaccination with an antibiotic-less version of BCGΔBCG1419c given to guinea pigs conferred a significant improvement in outcome following a low dose aerosol exposure to M. tuberculosis compared to that provided by a single dose of BCG Pasteur. BCGΔBCG1419c was more attenuated than BCG in murine macrophages, athymic, BALB/c, and C57BL/6 mice. In guinea pigs, BCGΔBCG1419c was at least as attenuated as BCG and induced similar dermal reactivity to that of BCG. Vaccination of guinea pigs with BCGΔBCG1419c resulted in increased anti-PPD IgG compared with those receiving BCG. Guinea pigs vaccinated with BCGΔBCG1419c showed a significant reduction of M. tuberculosis replication in lungs and spleens compared with BCG, as well as a significant reduction of pulmonary and extrapulmonary tuberculosis (TB) pathology measured using pathology scores recorded at necropsy. Evaluation of cytokines produced in lungs of infected guinea pigs showed that BCGΔBCG1419c significantly reduced TNF-α and IL-17 compared with BCG-vaccinated animals, with no changes in IL-10. This work demonstrates a significantly improved protection against pulmonary and extrapulmonary TB provided by BCGΔBCG1419c in susceptible guinea pigs together with an increased safety compared with BCG in several models. These results support the continued development of BCGΔBCG1419c as an effective vaccine for TB.
format	article
author	Michel de Jesús Aceves-Sánchez Mario Alberto Flores-Valdez César Pedroza-Roldán Elizabeth Creissen Linda Izzo Fabiola Silva-Angulo Clinton Dawson Angelo Izzo Helle Bielefeldt-Ohmann Cristian Alfredo Segura-Cerda Wendy López-Romero Jorge Bravo-Madrigal Jorge Alberto Barrios-Payán Miguel Ángel de la Cruz Miguel Ares María Guadalupe Jorge-Espinoza
author_facet	Michel de Jesús Aceves-Sánchez Mario Alberto Flores-Valdez César Pedroza-Roldán Elizabeth Creissen Linda Izzo Fabiola Silva-Angulo Clinton Dawson Angelo Izzo Helle Bielefeldt-Ohmann Cristian Alfredo Segura-Cerda Wendy López-Romero Jorge Bravo-Madrigal Jorge Alberto Barrios-Payán Miguel Ángel de la Cruz Miguel Ares María Guadalupe Jorge-Espinoza
author_sort	Michel de Jesús Aceves-Sánchez
title	Vaccination with BCGΔBCG1419c protects against pulmonary and extrapulmonary TB and is safer than BCG
title_short	Vaccination with BCGΔBCG1419c protects against pulmonary and extrapulmonary TB and is safer than BCG
title_full	Vaccination with BCGΔBCG1419c protects against pulmonary and extrapulmonary TB and is safer than BCG
title_fullStr	Vaccination with BCGΔBCG1419c protects against pulmonary and extrapulmonary TB and is safer than BCG
title_full_unstemmed	Vaccination with BCGΔBCG1419c protects against pulmonary and extrapulmonary TB and is safer than BCG
title_sort	vaccination with bcgδbcg1419c protects against pulmonary and extrapulmonary tb and is safer than bcg
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/5c59aca1dc2a4630bd0accb20d8195d8
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Vaccination with BCGΔBCG1419c protects against pulmonary and extrapulmonary TB and is safer than BCG

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