title: Novel therapeutic vaccine: granulysin and new DNA vaccine against Tuberculosis.
abstract: OBJECTIVE
  Multi-drug resistant (MDR) Mycobacterium Tuberculosis (M.TB) is a big problem in the world. We have developed novel TB therapeutic vaccines.
  
  
  RESULTS
  DNA vaccine expressing mycobacterial heat shock protein 65 and IL-12 was delivered by the hemagglutinating virus of Japan (HVJ)-envelope. M. TB, MDR-TB or extremenly drug resistant (XDR-TB) was injected i.v. into DBA/1 mice, and treated with the vaccine three times. This HVJ-E/Hsp65DNA+IL-12DNA vaccine provided strong therapeutic efficacy against MDR-TB and XDR-TB (prolongation of survival time and the decrease in the number of TB) in mice. Therapeutic effect of this vaccine on TB infection was also demonstrated in chronic TB infection murine model using aerosol infection intratracheally. On the other hand, granulysin protein produced from CTL has lethal activity against TB. Granulysin protein vaccine also exerted strong therapeutic effect. Furthermore, we extended our studies to monkey model, which is currently the best animal model of human TB. Hsp65DNA+IL-12 DNA vaccine exerted strong therapeutic efficacy (100% survival and augmentation of immune responses) in the TB-infected monkeys. In contrast, the survival of the saline control group was 60% at 16 week post-challenge. HVJ-Envelope/HSP65 DNA+IL-12 DNA vaccine increased the body weight of TB-infected monkeys, improved the erythrocyte sedimentation rate, and augmentated the immune responses (proliferation of PBL and IL-2 production). The enhancement of IL-2 production from monkeys treated with this vaccine was correlated with the therapeutic efficacy of the vaccine.
  
  
  CONCLUSIONS
  These data indicate that novel vaccines might be useful against TB including XDR-TB and MDR-TB for human therapeutic clinical trials.
authors.affiliation: Clinical Research Center, National Hospital Organization Kinki-chuo Chest Medical Center, Kitaku, Sakai, Osaka, Japan. okm@kch.hosp.go.jp
authors.forename: Masaji
authors.initials: M
authors.lastname: Okada
authors.forename: Yoko
authors.initials: Y
authors.lastname: Kita
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Nakajima
authors.forename: Noriko
authors.initials: N
authors.lastname: Kanamaru
authors.forename: Satomi
authors.initials: S
authors.lastname: Hashimoto
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Nagasawa
authors.forename: Yasufumi
authors.initials: Y
authors.lastname: Kaneda
authors.forename: Shigeto
authors.initials: S
authors.lastname: Yoshida
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Nishida
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Nakatani
authors.forename: Kyoko
authors.initials: K
authors.lastname: Takao
authors.forename: Chie
authors.initials: C
authors.lastname: Kishigami
authors.forename: Shiho
authors.initials: S
authors.lastname: Nishimatsu
authors.forename: Yuki
authors.initials: Y
authors.lastname: Sekine
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Inoue
authors.forename: Makoto
authors.initials: M
authors.lastname: Matsumoto
authors.forename: David N
authors.initials: DN
authors.lastname: McMurray
authors.forename: E C
authors.initials: EC
authors.lastname: De la Cruz
authors.forename: E V
authors.initials: EV
authors.lastname: Tan
authors.forename: R M
authors.initials: RM
authors.lastname: Abalos
authors.forename: J A
authors.initials: JA
authors.lastname: Burgos
authors.forename: Paul
authors.initials: P
authors.lastname: Saunderson
authors.forename: Mitsunori
authors.initials: M
authors.lastname: Sakatani
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000008:administration & dosage*; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology; D018834:Chaperonin 60 / Q000235:genetics / Q000276:immunology; D004195:Disease Models, Animal; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D018664:Interleukin-12 / Q000235:genetics; D008252:Macaca fascicularis; D018419:Primate Diseases / Q000382:microbiology / Q000628:therapy; D012376:Rodent Diseases / Q000382:microbiology / Q000628:therapy; D016019:Survival Analysis; D016896:Treatment Outcome; D032581:Tuberculosis Vaccines / Q000235:genetics / Q000276:immunology*; D018088:Tuberculosis, Multidrug-Resistant / Q000276:immunology / Q000628:therapy*; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D000945:Antigens, Differentiation, T-Lymphocyte; D001426:Bacterial Proteins; D018834:Chaperonin 60; C075005:GNLY protein, human; D032581:Tuberculosis Vaccines; D019444:Vaccines, DNA; C074119:heat-shock protein 65, Mycobacterium; D018664:Interleukin-12