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


CONCLUSIONS
In this study, we demonstrated that the novel rBCG2 vaccine may be a promising candidate vaccine against M. tuberculosis infection.
National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan, Miaoli, Taiwan.
Yih-Yuan
YY
Chen
National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan, Miaoli, Taiwan.
Chih-Wei
CW
Lin
National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan, Miaoli, Taiwan.
Wei-Feng
WF
Huang
National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan, Miaoli, Taiwan.
Jia-Ru
JR
Chang
National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan, Miaoli, Taiwan.
Ih-Jen
IJ
Su
National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan, Miaoli, Taiwan.
Chih-Hao
CH
Hsu
National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan, Miaoli, Taiwan.
Han-Yin
HY
Cheng
National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan, Miaoli, Taiwan.
Shu-Ching
SC
Hsu
National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan, Miaoli, Taiwan. Electronic address: hydou@nhri.org.tw.
Horng-Yunn
HY
Dou
D000217:Acyltransferases / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000235:genetics; D000818:Animals; D000942:Antigens, Bacterial / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D001426:Bacterial Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D058501:Enzyme-Linked Immunospot Assay; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000008:administration & dosage* / Q000235:genetics; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008168:Lung / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000382:microbiology; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D009163:Mycobacterium bovis / Q000235:genetics / Q000276:immunology*; D009169:Mycobacterium tuberculosis / Q000254:growth & development / Q000276:immunology; D013154:Spleen / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D014376:Tuberculosis / Q000517:prevention & control*; D032581:Tuberculosis Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
D000276:Adjuvants, Immunologic; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C117940:CFP-10 protein, Mycobacterium tuberculosis; D032581:Tuberculosis Vaccines; D014409:Tumor Necrosis Factor-alpha; D014614:Vaccines, Synthetic; D018664:Interleukin-12; D007371:Interferon-gamma; D000217:Acyltransferases; C121433:antigen 85B, Mycobacterium tuberculosis
Mycobacterium tuberculosis; recombinant bacille Calmette–Guerin; vaccine