title: Evaluation of a novel vaccine (HVJ-liposome/HSP65 DNA+IL-12 DNA) against tuberculosis using the cynomolgus monkey model of TB.
abstract: We have developed a novel tuberculosis (TB) vaccine; a combination of the DNA vaccines expressing mycobacterial heat shock protein 65 (HSP65) and interleukin 12 (IL-12) delivered by the hemagglutinating virus of Japan (HVJ)-liposome (HSP65+IL-12/HVJ). This vaccine provided remarkable protective efficacy in mouse and guinea pig models compared to the BCG vaccine, on the basis of an induction of the CTL activity and improvement of the histopathological tuberculosis lesions, respectively. Furthermore, we extended our studies to a cynomolgus monkey model, which is currently the best animal model of human tuberculosis. This novel vaccine provided a higher level of the protective efficacy than BCG based upon the assessment of mortality, the ESR, body weight, chest X-ray findings and immune responses. Furthermore, the combination of HSP65+IL-12/HVJ and BCG by the priming-booster method showed a synergistic effect in the TB-infected cynomolgus monkey (100% survival). These data indicate that our novel DNA vaccine might be useful against Mycobacterium tuberculosis for human clinical trials.
authors.affiliation: Clinical Research Center, National Hospital Organization Kinki-chuo Chest Medical Center,1180 Nagasone, Kitaku, Sakai, Osaka 591-8555, 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: Reiko
authors.initials: R
authors.lastname: Fukamizu
authors.forename: Yoshie
authors.initials: Y
authors.lastname: Tsunai
authors.forename: Ruriko
authors.initials: R
authors.lastname: Inoue
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Nakatani
authors.forename: Yumi
authors.initials: Y
authors.lastname: Namie
authors.forename: Junko
authors.initials: J
authors.lastname: Yamada
authors.forename: Kyoko
authors.initials: K
authors.lastname: Takao
authors.forename: Ritsuko
authors.initials: R
authors.lastname: Asai
authors.forename: Ryoko
authors.initials: R
authors.lastname: Asaki
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: Dela 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: Robert
authors.initials: R
authors.lastname: Gelber
authors.forename: Mitsunori
authors.initials: M
authors.lastname: Sakatani
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology*; D018833:Chaperonins / Q000235:genetics / Q000276:immunology*; D004195:Disease Models, Animal; D000882:Haplorhini; D018664:Interleukin-12 / Q000276:immunology*; D008081:Liposomes / Q000378:metabolism; D029082:Sendai virus; D014376:Tuberculosis / Q000517:prevention & control*; D032581:Tuberculosis Vaccines / Q000008:administration & dosage* / Q000276:immunology; D019444:Vaccines, DNA / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000276:immunology
chemical_list: D001426:Bacterial Proteins; D008081:Liposomes; D032581:Tuberculosis Vaccines; D019444:Vaccines, DNA; D014614:Vaccines, Synthetic; D018664:Interleukin-12; D018833:Chaperonins