2016年12月
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
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- 巻
- 34
- 号
- 50
- 開始ページ
- 6301
- 終了ページ
- 6308
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1016/j.vaccine.2016.10.069
- 出版者・発行元
- ELSEVIER SCI LTD
Enhancement of the T cell-stimulating ability of Mycobacterium bovis BCG (BCG) is necessary to develop an effective tuberculosis vaccine. For this purpose, we introduced the PEST-HSP70-major membrane protein-II (MMPII)-PEST fusion gene into ureC-gene depleted recombinant (r) BCG to produce BCG-PEST. The PEST sequence is involved in the proteasomal processing of antigens. BCG-PEST secreted the PEST-HSP70-MMPII-PEST fusion protein and more efficiently activated human monocyte-derived dendritic cells (DCs) in terms of phenotypic changes and cytokine productions than an empty-vector introduced BCG or HSP7O-MMPII gene-introduced ureC gene-depleted BCG (BCG-DHTM). Autologous human naive CD8(+) T cells and naive CD4(+) T cells were effectively activated by BCG-PEST and produced IFN-gamma in an antigen-specific manner through DCs. These T cell activations were closely associated with phagosomal maturation and intraproteasomal protein degradation in antigen-presenting cells. Furthermore, BCG-PEST produced long-lasting memory-type T cells in C57BL/6 mice more efficiently than control rBCGs. Moreover, a single subcutaneous injection of BCG-PEST more effectively reduced the multiplication of subsequent aerosol-challenged Mycobacterium tuberculosis of the standard H37Rv strain and clinically isolated Beijing strain in the lungs than control rBCGs. The vaccination effect of BCG-PEST lasted for at least 6 months. These results indicate that BCG-PEST may be able to efficiently control the spread of tuberculosis in human. (C) 2016 Elsevier Ltd. All rights reserved.
- リンク情報
- ID情報
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- DOI : 10.1016/j.vaccine.2016.10.069
- ISSN : 0264-410X
- eISSN : 1873-2518
- PubMed ID : 27847173
- Web of Science ID : WOS:000390622600030