title: Defined tuberculosis vaccine, Mtb72F/AS02A, evidence of protection in cynomolgus monkeys.
abstract: The development of a vaccine for tuberculosis requires a combination of antigens and adjuvants capable of inducing appropriate and long-lasting T cell immunity. We evaluated Mtb72F formulated in AS02A in the cynomolgus monkey model. The vaccine was immunogenic and caused no adverse reactions. When monkeys were immunized with bacillus Calmette-Guérin (BCG) and then boosted with Mtb72F in AS02A, protection superior to that afforded by using BCG alone was achieved, as measured by clinical parameters, pathology, and survival. We observed long-term survival and evidence of reversal of disease progression in monkeys immunized with the prime-boost regimen. Antigen-specific responses from protected monkeys receiving BCG and Mtb72F/AS02A had a distinctive cytokine profile characterized by an increased ratio between 3 Th1 cytokines, IFN-gamma, TNF, and IL-2 and an innate cytokine, IL-6. To our knowledge, this is an initial report of a vaccine capable of inducing long-term protection against tuberculosis in a nonhuman primate model, as determined by protection against severe disease and death, and by other clinical and histopathological parameters.
authors.affiliation: Corixa Corporation, Seattle, WA 98104, USA. sreed@idri.org
authors.forename: Steven G
authors.initials: SG
authors.lastname: Reed
authors.forename: Rhea N
authors.initials: RN
authors.lastname: Coler
authors.forename: Wilfried
authors.initials: W
authors.lastname: Dalemans
authors.forename: Wilifred
authors.initials: W
authors.lastname: Dalemans
authors.forename: Esterlina V
authors.initials: EV
authors.lastname: Tan
authors.forename: Eduardo C
authors.initials: EC
authors.lastname: DeLa Cruz
authors.forename: Randall J
authors.initials: RJ
authors.lastname: Basaraba
authors.forename: Ian M
authors.initials: IM
authors.lastname: Orme
authors.forename: Yasir A W
authors.initials: YA
authors.lastname: Skeiky
authors.forename: Mark R
authors.initials: MR
authors.lastname: Alderson
authors.forename: Karen D
authors.initials: KD
authors.lastname: Cowgill
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Prieels
authors.forename: Rodolfo M
authors.initials: RM
authors.lastname: Abalos
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Dubois
authors.forename: Joe
authors.initials: J
authors.lastname: Cohen
authors.forename: Pascal
authors.initials: P
authors.lastname: Mettens
authors.forename: Yves
authors.initials: Y
authors.lastname: Lobet
mesh_terms: D000276:Adjuvants, Immunologic / Q000737:chemistry; D000818:Animals; D016207:Cytokines / Q000378:metabolism; D018450:Disease Progression; D000882:Haplorhini; D007107:Immune System; D007371:Interferon-gamma / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008252:Macaca fascicularis; D009169:Mycobacterium tuberculosis / Q000378:metabolism; D013997:Time Factors; D016896:Treatment Outcome; D014376:Tuberculosis / Q000382:microbiology / Q000517:prevention & control*; D032581:Tuberculosis Vaccines / Q000737:chemistry / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D016207:Cytokines; D015850:Interleukin-6; C539343:Mtb72F-AS02A vaccine; D032581:Tuberculosis Vaccines; D007371:Interferon-gamma