14 October 2014
Background: Immunological parameters induced by BCG and the requirement of immunologic responses for optimal vaccine efficacy is incompletely understood.
Results: Small-molecule inhibitors of Th2 and Treg cells promote BCG vaccine efficacy.
Conclusion: Immunomodulators enhance the capacity of the BCG vaccine to protect against tuberculosis.
Significance: Our studies reveal a simple and cost-effective approach to improve BCG vaccine efficacy.
Tuberculosis affects nine million individuals and kills almost two million people every year. The only vaccine available, Bacillus Calmette-Guerin (BCG), has been used since its inception in 1921. Although BCG induces host-protective T helper 1 (Th1) cell immune responses, which play a central role in host protection, its efficacy is unsatisfactory, suggesting that additional methods to enhance protective immune responses are needed. Recently we have shown that simultaneous inhibition of Th2 cells and Tregs by using the pharmacological inhibitors suplatast tosylate and D4476, respectively, dramatically enhances Mycobacterium tuberculosis clearance and induces superior Th1 responses. Here we show that treatment with these two drugs during BCG vaccination dramatically improves vaccine efficacy. Furthermore, we demonstrate that these drugs induce a shift in the development of T cell memory, favoring central memory T (Tcm) cell responses over effector memory T (Tem) cell responses. Collectively, our findings provide evidence that simultaneous inhibition of Th2 cells and Tregs during BCG vaccination promotes vaccine efficacy.