Evaluation of Early Innate and Adaptive Immune Responses to the TB Vaccine Mycobacterium Bovis BCG and Vaccine Candidate BCGdBCG1419c

Abstract The vaccine Mycobacterium bovis Bacillus Calmette–Guérin (BCG) elicits an immune response that is protective against certain forms of tuberculosis (TB); however, because BCG efficacy is limited it is important to identify alternative TB vaccine candidates. Recently, the BCG deletion mutant and vaccine candidate BCGDBCG1419c was demonstrated to survive longer in intravenously infected BALB/c mice due to enhanced biofilm formation, and better protected both BALB/c and C57BL/6 mice against TB-induced lung pathology during chronic stages of infection, relative to BCG controls. BCGDBCG1419c-elicited protection also associated with lower levels of proinflammatory cytokines (i.e. IL6, TNFa) at the site of infection in C57BL/6 mice. Given the distinct immune profiles of BCG- and BCGDBCG1419c-immunized mice during chronic TB, we set out to determine if there are early immunological events which distinguish these two groups, using multi-dimensional flow cytometric analysis of the lungs and other tissues soon after immunization. Our results demonstrate a number of innate and adaptive response differences between BCG- and BCGDBCG1419c-immunized mice which are consistent with the latter being longer lasting and potentially less inflammatory, including lower frequencies of exhausted CD4 + T helper (T H ) cells and higher frequencies of IL10-producing T cells, respectively. These studies suggest the use of BCGDBCG1419c may be advantageous as an alternative TB vaccine candidate.