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We have constructed rBCG strains expressing LTAK63 at different expression levels. Mice immunized with BCG expressing low levels of LTAK63 (rBCG-LTAK63<jats:sub>lo<\/jats:sub>) showed higher Th1 cytokines and IL-17 in the lungs, and when challenged intratracheally with <jats:italic>Mycobacterium tuberculosis<\/jats:italic> displayed a 2.0\u20133.0\u2009log reduction in CFU as compared to wild type BCG. Histopathological analysis of lung tissues from protected mice revealed a reduced inflammatory response. Immunization with rBCG-LTAK63<jats:sub>lo<\/jats:sub> also protected against a 100-fold higher challenge dose. Mice immunized with rBCG-LTAK63<jats:sub>lo<\/jats:sub> produced an increase in TGF-\u03b2 as compared with BCG after challenge, with a corresponding reduction in Th1 and Th17 cytokines, as determined by Real Time RT-PCR. Furthermore, rBCG-LTAK63<jats:sub>lo<\/jats:sub> also displays protection against challenge with a highly virulent Beijing isolate. Our findings suggest that BCG with low-level expression of the LTAK63 adjuvant induces a stronger immune response in the lungs conferring higher levels of protection, and a novel mechanism subsequently triggers a regulatory immune response, which then limits the pathology. The rBCG-LTAK63<jats:sub>lo<\/jats:sub> strain can be the basis of an improved vaccine against tuberculosis.<\/jats:p>","DOI":"10.1038\/s41598-017-02003-9","type":"journal-article","created":{"date-parts":[[2017,5,12]],"date-time":"2017-05-12T13:13:16Z","timestamp":1494594796000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Recombinant BCG Expressing LTAK63 Adjuvant induces Superior Protection against Mycobacterium tuberculosis"],"prefix":"10.1038","volume":"7","author":[{"given":"Ivan P.","family":"Nascimento","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dunia","family":"Rodriguez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carina C.","family":"Santos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo P.","family":"Amaral","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrique K.","family":"Rofatto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana P.","family":"Junqueira-Kipnis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo D. 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