Novel prophylactic and therapeutic vaccine against tuberculosis.
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.
Okada
Masaji
M
Clinical Research Center, National Hospital Organization Kinki-chuo Chest Medical Center, 1180 Nagasone, Kitaku, Sakai, Osaka 591-8555, Japan. okm@kch.hosp.go.jp
Kita
Yoko
Y
Nakajima
Toshihiro
T
Kanamaru
Noriko
N
Hashimoto
Satomi
S
Nagasawa
Tetsuji
T
Kaneda
Yasufumi
Y
Yoshida
Shigeto
S
Nishida
Yasuko
Y
Nakatani
Hitoshi
H
Takao
Kyoko
K
Kishigami
Chie
C
Inoue
Yoshikazu
Y
Matsumoto
Makoto
M
McMurray
David N
DN
Dela Cruz
E C
EC
Tan
E V
EV
Abalos
R M
RM
Burgos
J A
JA
Saunderson
Paul
P
Sakatani
Mitsunori
M
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*
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