title: Novel prophylactic and therapeutic vaccine against tuberculosis.
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)-envelope and -liposome (HSP65+IL-12/HVJ). This vaccine provided therapeutic efficacy as well as remarkable protective efficacy via CD8(+) T and CD4(+) T cells in murine models compared with the saline controls, on the basis of CFU of number of multi-drug resistant TB (MDR-TB), and survival of extremely drug resistant TB (XDR-TB) challenged mice. Furthermore, we extended our studies to a cynomolgus monkey model, which is currently the best animal model of human tuberculosis. This vaccine exerted therapeutic efficacy (survival and immune responses) in the TB-infected monkeys. These data indicate that our novel DNA vaccine might be useful against Mycobacterium tuberculosis including XDR-TB and MDR-TB for human therapeutic 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: 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: 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: 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: Paul
authors.initials: P
authors.lastname: Saunderson
authors.forename: Mitsunori
authors.initials: M
authors.lastname: Sakatani
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology*; D016827:CD8 Antigens / Q000276:immunology; D018834:Chaperonin 60; D018833:Chaperonins / Q000235:genetics / Q000276:immunology*; D024901:Drug Resistance, Multiple, Bacterial; D018664:Interleukin-12 / Q000235:genetics / Q000276:immunology*; D008168:Lung / Q000382:microbiology; D008252:Macaca fascicularis; D051379:Mice; D014376:Tuberculosis / Q000628:therapy*; D032581:Tuberculosis Vaccines / Q000276:immunology / Q000627:therapeutic use*; D014611:Vaccination; D019444:Vaccines, DNA / Q000276:immunology / Q000627:therapeutic use*
chemical_list: D001426:Bacterial Proteins; D016827:CD8 Antigens; D018834:Chaperonin 60; D032581:Tuberculosis Vaccines; D019444:Vaccines, DNA; C074119:heat-shock protein 65, Mycobacterium; D018664:Interleukin-12; D018833:Chaperonins