title: Novel therapeutic vaccines [(HSP65 + IL-12)DNA-, granulysin- and Ksp37-vaccine] against tuberculosis and synergistic effects in the combination with chemotherapy.
abstract: OBJECTIVE
  Multi-drug resistant tuberculosis (MDR-TB) and extremely drug resistant (XDR) TB are big problems in the world. We have developed novel TB therapeutic vaccines, HVJ-Envelope/HSP65 + IL-12 DNA vaccine (HSP65-vaccine), granulysin vaccine and killer specific secretory protein of 37kDa (Ksp37) vaccine.
  
  
  RESULTS
  HSP65 vaccine showed strong therapeutic effect against both MDR-TB and XDR-TB in mice. Intradermal immunization of HSP65-vaccine showed stronger therapeutic effect against TB than intramuscular or subcutaneous immunization. Furthermore, the synergistic therapeutic effect was observed when the vaccine was administrated in combination with Isoniazid (INH), which is a first line drug for chemotherapy. The combination of types of vaccines (HSP65- and granulysin- vaccines) also showed synergistic therapeutic effect. In the monkey model, granulysin-vaccine prolonged the survival period after the infection of TB and long-term survival was observed in vaccine-treated group. We examined the potential of two kinds of novel DNA vaccines (Ksp37-vaccine and granulysin-vaccine). Both vaccines augmented in vivo differentiation of CTL against TB. We measured the amount of Ksp37 protein in human serum and revealed that the level of Ksp37 protein of patients with tuberculosis was lower than that of healthy volunteers. Therefore, we established Ksp37 transgenic mice as well as granulysin transgenic mice to elucidate the function of those proteins. Both transgenic mice were resistant to TB infection.
  
  
  CONCLUSIONS
  These data indicate the potential of combinational therapy; the combination of two DNA vaccines or combination of DNA vaccine with antibiotic drug. Thus, it will provide a novel strategy for the treatment of MDR-TB.
authors.affiliation: Clinical Research Center; National Hospital Organization Kinki-chuo Chest Medical Center; Kitaku, Sakai Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Kita
authors.forename: Satomi
authors.initials: S
authors.lastname: Hashimoto
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Nakajima
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Nakatani
authors.forename: Shiho
authors.initials: S
authors.lastname: Nishimatsu
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Nishida
authors.forename: Noriko
authors.initials: N
authors.lastname: Kanamaru
authors.forename: Yasuhumi
authors.initials: Y
authors.lastname: Kaneda
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Takamori
authors.forename: David
authors.initials: D
authors.lastname: McMurray
authors.forename: Esterlina V
authors.initials: EV
authors.lastname: Tan
authors.forename: Marjorie L
authors.initials: ML
authors.lastname: Cang
authors.forename: Paul
authors.initials: P
authors.lastname: Saunderson
authors.forename: E C
authors.initials: EC
authors.lastname: Dela Cruz
authors.forename: Masaji
authors.initials: M
authors.lastname: Okada
mesh_terms: D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics / Q000276:immunology; D000995:Antitubercular Agents / Q000627:therapeutic use*; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology*; D001798:Blood Proteins / Q000235:genetics / Q000276:immunology; D018834:Chaperonin 60 / Q000235:genetics / Q000276:immunology*; D003131:Combined Modality Therapy / Q000379:methods; D004195:Disease Models, Animal; D018664:Interleukin-12 / Q000235:genetics / Q000276:immunology; D008252:Macaca fascicularis; D008822:Mice, Transgenic; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D016896:Treatment Outcome; D014376:Tuberculosis / Q000628:therapy*; D032581:Tuberculosis Vaccines / Q000008:administration & dosage / Q000276:immunology*; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D000945:Antigens, Differentiation, T-Lymphocyte; D000995:Antitubercular Agents; D001426:Bacterial Proteins; D001798:Blood Proteins; D018834:Chaperonin 60; C431908:FGFBP2 protein, human; C075005:GNLY protein, human; D032581:Tuberculosis Vaccines; D019444:Vaccines, DNA; C074119:heat-shock protein 65, Mycobacterium; D018664:Interleukin-12