Evaluation of a novel vaccine (HVJ-liposome/HSP65 DNA+IL-12 DNA) against tuberculosis using the cynomolgus monkey model of TB.
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.
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
Fukamizu
Reiko
R
Tsunai
Yoshie
Y
Inoue
Ruriko
R
Nakatani
Hitoshi
H
Namie
Yumi
Y
Yamada
Junko
J
Takao
Kyoko
K
Asai
Ritsuko
R
Asaki
Ryoko
R
Matsumoto
Makoto
M
McMurray
David N
DN
Dela Cruz
E C
EC
Tan
E V
EV
Abalos
R M
RM
Burgos
J A
JA
Gelber
Robert
R
Sakatani
Mitsunori
M
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
D001426:Bacterial Proteins; D008081:Liposomes; D032581:Tuberculosis Vaccines; D019444:Vaccines, DNA; D014614:Vaccines, Synthetic; D018664:Interleukin-12; D018833:Chaperonins