Simultaneous Inhibition of T Helper 2 and T Regulatory Cell Differentiation by Small Molecules Enhances Bacillus Calmette-Guerin Vaccine Efficacy against Tuberculosis |
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| Authors: | Debapriya Bhattacharya Ved Prakash Dwivedi Santosh Kumar Madhava C Reddy Luc Van Kaer Prashini Moodley Gobardhan Das |
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| Institution: | From the ‡Laboratory Medicine and Medical Sciences, College of Health Sciences, University of Kwazulu Natal, Durban 4001, South Africa, ;§Yogi Vemana University, Kadapa 516003, India, ;¶Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, and ;‖Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi 110067, India |
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| Abstract: | 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. |
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| Keywords: | Cytokine Immunotherapy Mycobacterium tuberculosis T Helper Cells Vaccine |
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