論文

査読有り
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
  • Yumiko Tsukamoto
  • ,
  • Yumi Maeda
  • ,
  • Toshiki Tamura
  • ,
  • Tetsu Mukai
  • ,
  • Satoshi Mitarai
  • ,
  • Saburo Yamamoto
  • ,
  • Masahiko Makino

34
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
DOI
https://doi.org/10.1016/j.vaccine.2016.10.069
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/27847173
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000390622600030&DestApp=WOS_CPL
ID情報
  • DOI : 10.1016/j.vaccine.2016.10.069
  • ISSN : 0264-410X
  • eISSN : 1873-2518
  • PubMed ID : 27847173
  • Web of Science ID : WOS:000390622600030

エクスポート
BibTeX RIS