Novel recombinant BCG and DNA-vaccination against tuberculosis in a cynomolgus monkey model.
We have developed two novel tuberculosis (TB) vaccines: a DNA vaccine combination expressing mycobacterial heat shock protein 65 (Hsp65) and interleukin-12 (IL-12) by using the hemagglutinating virus of Japan (HVJ)-liposome (HSP65+IL-12/HVJ) and a recombinant BCG harboring the 72f fusion gene (72f rBCG). These vaccines provide remarkable protective efficacy in mouse and guinea pig models, as compared to the current by available BCG vaccine. In the present study, we extended our studies to a cynomolgus monkey model, which is currently the best animal model of human tuberculosis, to evaluate the HSP65+IL-12/HVJ and 72f rBCG vaccines. Vaccination with HSP65+IL-12/HVJ as well as 72f rBCG vaccines provided better protective efficacy as assessed by the Erythrocyte Sedimentation Rate, chest X-ray findings and immune responses than BCG. Most importantly, HSP65+IL-12/HVJ resulted in an increased survival for over a year. This is the first report of successful DNA vaccination and recombinant BCG vaccination against M. tuberculosis in the monkey model.
Kita
Yoko
Y
Clinical Research Center, National Hospital Organization Kinki-chuo Chest Medical Center, 1180 Nagasone, Sakai, Osaka 591-8555, Japan.
Tanaka
Takao
T
Yoshida
Shigeto
S
Ohara
Naoya
N
Kaneda
Yasufumi
Y
Kuwayama
Sachiko
S
Muraki
Yumiko
Y
Kanamaru
Noriko
N
Hashimoto
Satomi
S
Takai
Hiroko
H
Okada
Chika
C
Fukunaga
Yukari
Y
Sakaguchi
Yayoi
Y
Furukawa
Izumi
I
Yamada
Kyoko
K
Inoue
Yoshikazu
Y
Takemoto
Yuji
Y
Naito
Mariko
M
Yamada
Takeshi
T
Matsumoto
Makoto
M
McMurray
David N
DN
Cruz
E C Dela
EC
Tan
E V
EV
Abalos
R M
RM
Burgos
J A
JA
Gelber
Robert
R
Skeiky
Yasir
Y
Reed
Steven
S
Sakatani
Mitsunori
M
Okada
Masaji
M
D000818:Animals; D001500:BCG Vaccine / Q000235:genetics / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology; D018834:Chaperonin 60; D018833:Chaperonins / Q000235:genetics / Q000276:immunology; D004195:Disease Models, Animal; D006168:Guinea Pigs; D006801:Humans; D018664:Interleukin-12 / Q000235:genetics; D008081:Liposomes; D008252:Macaca fascicularis; D051379:Mice; D029082:Sendai virus / Q000235:genetics; D032581:Tuberculosis Vaccines / Q000235:genetics / Q000494:pharmacology*; D014397:Tuberculosis, Pulmonary / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D019444:Vaccines, DNA / Q000235:genetics / Q000494:pharmacology; D014614:Vaccines, Synthetic / Q000235:genetics / Q000494:pharmacology
D001500:BCG Vaccine; D001426:Bacterial Proteins; D018834:Chaperonin 60; D008081:Liposomes; D032581:Tuberculosis Vaccines; D019444:Vaccines, DNA; D014614:Vaccines, Synthetic; C074119:heat-shock protein 65, Mycobacterium; D018664:Interleukin-12; D018833:Chaperonins