TY - JOUR AU - Flores-Valdez, Mario A. AU - Pedroza-Roldán, César AU - Aceves-Sánchez, Michel de Jesús AU - Peterson, Eliza J. R. AU - Baliga, Nitin S. AU - Hernández-Pando, Rogelio AU - Troudt, JoLynn AU - Creissen, Elizabeth AU - Izzo, Linda AU - Bielefeldt-Ohmann, Helle AU - Bickett, Thomas AU - Izzo, Angelo A. PY - 2018 M3 - Original Research TI - The BCGΔBCG1419c Vaccine Candidate Reduces Lung Pathology, IL-6, TNF-α, and IL-10 During Chronic TB Infection JO - Frontiers in Microbiology UR - https://www.frontiersin.org/articles/10.3389/fmicb.2018.01281 VL - 9 SN - 1664-302X N2 - Mycobacterium tuberculosis (M. tuberculosis), the causative agent of human tuberculosis (TB), is estimated to be harbored by up to 2 billion people in a latent TB infection (LTBI) state. The only TB vaccine approved for use in humans, BCG, does not confer protection against establishment of or reactivation from LTBI, so new vaccine candidates are needed to specifically address this need. Following the hypothesis that mycobacterial biofilms resemble aspects of LTBI, we modified BCG by deleting the BCG1419c gene to create the BCGΔBCG1419c vaccine strain. In this study, we compared cytokine profiles, bacterial burden, and lung lesions after immunization with BCG or BCGΔBCG1419c before and after 6 months of aerosol infection with M. tuberculosis H37Rv in the resistant C57BL/6 mouse model. Our results show that in infected mice, BCGΔBCG1419c significantly reduced lung lesions and IL-6 in comparison to the unmodified BCG strain, and was the only vaccine that decreased production of TNF-α and IL-10 compared to non-vaccinated mice, while vaccination with BCG or BCGΔBCG1419c significantly reduced IFN-γ production. Moreover, transcriptome profiling of BCGΔBCG1419c suggests that compared to BCG, it has decreased expression of genes involved in mycolic acids (MAs) metabolism, and antigenic chaperones, which might be involved in reduced pathology compared to BCG-vaccinated mice. ER -