Enhanced protective efficacy against tuberculosis provided by a recombinant urease deficient BCG expressing heat shock protein 70-major membrane protein-II having PEST sequence

Vaccine ◽  
2016 ◽  
Vol 34 (50) ◽  
pp. 6301-6308 ◽  
Author(s):  
Yumiko Tsukamoto ◽  
Yumi Maeda ◽  
Toshiki Tamura ◽  
Tetsu Mukai ◽  
Satoshi Mitarai ◽  
...  
2010 ◽  
Vol 48 (1-3) ◽  
pp. 191-202 ◽  
Author(s):  
Fumito Tani ◽  
Satoshi Nishikawa ◽  
Itsumi Yokoyama ◽  
Kei Hashimoto ◽  
Masahiro Nakamoto ◽  
...  

2013 ◽  
Vol 21 (1) ◽  
pp. 1-11 ◽  
Author(s):  
Tetsu Mukai ◽  
Yumiko Tsukamoto ◽  
Yumi Maeda ◽  
Toshiki Tamura ◽  
Masahiko Makino

ABSTRACTFor the purpose of obtainingMycobacterium bovisbacillus Calmette-Guérin (BCG) capable of activating human naive T cells, urease-deficient BCG expressing a fusion protein composed ofMycobacterium tuberculosis-derived major membrane protein II (MMP-II) and heat shock protein 70 (HSP70) of BCG (BCG-DHTM) was produced. BCG-DHTM secreted the HSP70-MMP-II fusion protein and effectively activated human monocyte-derived dendritic cells (DCs) by inducing phenotypic changes and enhanced cytokine production. BCG-DHTM-infected DCs activated naive T cells of both CD4 and naive CD8 subsets, in an antigen (Ag)-dependent manner. The T cell activation induced by BCG-DHTM was inhibited by the pretreatment of DCs with chloroquine. The naive CD8+T cell activation was mediated by the transporter associated with antigen presentation (TAP) and the proteosome-dependent cytosolic cross-priming pathway. Memory CD8+T cells and perforin-producing effector CD8+T cells were efficiently produced from the naive T cell population by BCG-DHTM stimulation. Single primary infection with BCG-DHTM in C57BL/6 mice efficiently produced T cells responsive toin vitrosecondary stimulation with HSP70, MMP-II, andM. tuberculosis-derived cytosolic protein and inhibited the multiplication of subsequently aerosol-challengedM. tuberculosismore efficiently than did vector control BCG. These results indicate that the introduction of MMP-II and HSP70 into urease-deficient BCG may be useful for improving BCG for control of tuberculosis.


2014 ◽  
Vol 1838 (5) ◽  
pp. 1344-1361 ◽  
Author(s):  
Ajay K. Mahalka ◽  
Thomas Kirkegaard ◽  
Laura T.I. Jukola ◽  
Marja Jäättelä ◽  
Paavo K.J. Kinnunen

2001 ◽  
Vol 120 (5) ◽  
pp. A152-A152
Author(s):  
H SUZUKI ◽  
S NAGAHASHI ◽  
M MIYAZAWA ◽  
M MORI ◽  
H NAGATA ◽  
...  

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