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BCG\u0394BCG1419c was more attenuated than BCG in murine macrophages, athymic, BALB\/c, and C57BL\/6 mice. In guinea pigs, BCG\u0394BCG1419c was at least as attenuated as BCG and induced similar dermal reactivity to that of BCG. Vaccination of guinea pigs with BCG\u0394BCG1419c resulted in increased anti-PPD IgG compared with those receiving BCG. Guinea pigs vaccinated with BCG\u0394BCG1419c showed a significant reduction of <jats:italic>M. tuberculosis<\/jats:italic> 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 BCG\u0394BCG1419c significantly reduced TNF-\u03b1 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 BCG\u0394BCG1419c in susceptible guinea pigs together with an increased safety compared with BCG in several models. These results support the continued development of BCG\u0394BCG1419c as an effective vaccine for TB.<\/jats:p>","DOI":"10.1038\/s41598-021-91993-8","type":"journal-article","created":{"date-parts":[[2021,6,14]],"date-time":"2021-06-14T10:03:10Z","timestamp":1623664990000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Vaccination with BCG\u0394BCG1419c protects against pulmonary and extrapulmonary TB and is safer than BCG"],"prefix":"10.1038","volume":"11","author":[{"given":"Michel de Jes\u00fas","family":"Aceves-S\u00e1nchez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario Alberto","family":"Flores-Valdez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9sar","family":"Pedroza-Rold\u00e1n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Creissen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"Izzo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabiola","family":"Silva-Angulo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clinton","family":"Dawson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelo","family":"Izzo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helle","family":"Bielefeldt-Ohmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristian Alfredo","family":"Segura-Cerda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wendy","family":"L\u00f3pez-Romero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge","family":"Bravo-Madrigal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge Alberto","family":"Barrios-Pay\u00e1n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel \u00c1ngel","family":"de la Cruz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel","family":"Ares","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Guadalupe","family":"Jorge-Espinoza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,6,14]]},"reference":[{"key":"91993_CR1","unstructured":"World Health Organization. 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