title: Novel recombinant BCG and DNA-vaccination against tuberculosis in a cynomolgus monkey model.
abstract: 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.
authors.affiliation: Clinical Research Center, National Hospital Organization Kinki-chuo Chest Medical Center, 1180 Nagasone, Sakai, Osaka 591-8555, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Kita
authors.forename: Takao
authors.initials: T
authors.lastname: Tanaka
authors.forename: Shigeto
authors.initials: S
authors.lastname: Yoshida
authors.forename: Naoya
authors.initials: N
authors.lastname: Ohara
authors.forename: Yasufumi
authors.initials: Y
authors.lastname: Kaneda
authors.forename: Sachiko
authors.initials: S
authors.lastname: Kuwayama
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Muraki
authors.forename: Noriko
authors.initials: N
authors.lastname: Kanamaru
authors.forename: Satomi
authors.initials: S
authors.lastname: Hashimoto
authors.forename: Hiroko
authors.initials: H
authors.lastname: Takai
authors.forename: Chika
authors.initials: C
authors.lastname: Okada
authors.forename: Yukari
authors.initials: Y
authors.lastname: Fukunaga
authors.forename: Yayoi
authors.initials: Y
authors.lastname: Sakaguchi
authors.forename: Izumi
authors.initials: I
authors.lastname: Furukawa
authors.forename: Kyoko
authors.initials: K
authors.lastname: Yamada
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Inoue
authors.forename: Yuji
authors.initials: Y
authors.lastname: Takemoto
authors.forename: Mariko
authors.initials: M
authors.lastname: Naito
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yamada
authors.forename: Makoto
authors.initials: M
authors.lastname: Matsumoto
authors.forename: David N
authors.initials: DN
authors.lastname: McMurray
authors.forename: E C Dela
authors.initials: EC
authors.lastname: 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: Yasir
authors.initials: Y
authors.lastname: Skeiky
authors.forename: Steven
authors.initials: S
authors.lastname: Reed
authors.forename: Mitsunori
authors.initials: M
authors.lastname: Sakatani
authors.forename: Masaji
authors.initials: M
authors.lastname: Okada
mesh_terms: 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
chemical_list: 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