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.