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Novel Therapeutic Vaccination(granulysin DNA, adenoviral vector/IL‐6 related genes) against Tuberculosis
Author(s) -
Okada Masaji,
Kita Yoko,
Kanamaru Noriko,
Hashimoto Satomi,
Nishida Yasuko,
Nakatani Hitoshi,
Takao Kyoko,
Kishigami Chie,
Takamori Yasushi,
Saito Izumu
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.2_supplement.491
Subject(s) - granulysin , ctl* , dna vaccination , virology , tuberculosis , biology , genetic enhancement , gene , viral vector , immunology , tuberculosis vaccines , vaccination , immune system , medicine , perforin , mycobacterium tuberculosis , immunization , recombinant dna , cd8 , genetics , pathology
We have developed novel therapeutic tuberculosis (TB) vaccines: IL‐6 related genes (IL‐6 gene + IL‐6 receptor gene + gp130 gene using adenovirus vector) and granulysin DNA gene. IL‐6 related DNA vaccine provided remarkable therapeutic efficacy in BALB/c mouse, on the basis of an induction of the CTL activity and improvement of the histopathological tuberculosis lesions, respectively. The number of live TB in lungs from mice treated with IL‐6 related genes therapy was smaller than that from the control mice treated with BCG Tokyo. CTL activity against TB was enhanced by the assay for detecting the production of IFN‐g from effecter lymphocytes stimulated with PPD or killed TB. The histopathological findings in the lungs derived from mice treated with IL‐6 related genes were improved. Furthermore, we established granulysin DNA vaccine. Human granulysin cDNA was constructed into pcDLSRα DNA. The number of live TB in lungs, spleens and liver treated with granulysin DNA therapy even after the challenge of TB was smaller than that from the control mice (non‐treated mice). Synergistic therapeutic effect of granulysin DNA and IL‐6 realated genes is now being studied. These vaccines should provide strong tools for therapy against Multi‐drug resistant tuberculosis. [H‐17‐Shinko‐5] of Research on Emerging and Re‐emerging Infectious Diseases in Health Sciences Research grants from Japan.