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Volume 50, Number 1, February 2017

Recombinant bacille Calmette–Guerin coexpressing Ag85b, CFP10, and interleukin-12 elicits effective protection against Mycobacterium tuberculosis 


Yih-Yuan Chen, Chih-Wei Lin, Wei-Feng Huang, Jia-Ru Chang, Ih-Jen Su, Chih-Hao Hsu, Han-Yin Cheng, Shu-Ching Hsu, Horng-Yunn Dou


 

Corresponding author:

Horng-Yunn Dou, Corresponding author. National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Number 35, Keyan Road, Zhunan Town, Miaoli County 350, Taiwan, ROC. 



 

Background and purpose: 

The tuberculosis (TB) pandemic remains a leading cause of human morbidity and mortality, despite widespread use of the only licensed anti-TB vaccine, bacille Calmette-Guerin (BCG). The protective efficacy of BCG in preventing pulmonary TB is highly variable; therefore, an effective new vaccine is urgently required. 



 

Methods:

In the present study, we assessed the ability of novel recombinant BCG vaccine (rBCG) against Mycobacterium tuberculosis by using modern immunological methods. 



 

Results:

Enzyme-linked immunospot assays demonstrated that the rBCG vaccine, which coexpresses two mycobacterial antigens (Ag85B and CFP10) and human interleukin (IL)-12 (rBCG2) elicits greater interferon-γ (IFN-γ) release in the mouse lung and spleen, compared to the parental BCG. In addition, rBCG2 triggers a Th1-polarized response. Our results also showed that rBCG2 vaccination significantly limits M. tuberculosis H37Rv multiplication in macrophages. The rBCG2 vaccine surprisingly induces significantly higher tumor necrosis factor-α (TNF-α) production by peripheral blood mononuclear cells that were exposed to a nonmycobacterial stimulus, compared to the parental BCG. 



 

Conclusion:

In this study, we demonstrated that the novel rBCG2 vaccine may be a promising candidate vaccine against M. tuberculosis infection. 



 

Key words:

Mycobacterium tuberculosis, recombinant bacille Calmette–Guerin, vaccine