title: Lack of protection in mice and necrotizing bronchointerstitial pneumonia with bronchiolitis in guinea pigs immunized with vaccines directed against the hsp60 molecule of Mycobacterium tuberculosis.
abstract: In this study, the hsp60 and hsp70 heat shock protein antigens of Mycobacterium tuberculosis were tested as potential vaccine candidates, using purified recombinant protein antigens or antigens encoded in the form of a DNA plasmid vaccine. Guinea pigs vaccinated with a mixture of the two proteins showed no evidence of resistance to low-dose aerosol challenge infection and quickly developed severe lung damage characterized by necrotizing bronchointerstitial pneumonia and bronchiolitis. As a result, we turned instead to a DNA vaccination approach using a plasmid encoding the hsp60 antigen of M. tuberculosis. Although immunogenic in mice, vaccination with plasmid DNA encoding hsp60 was not protective in that model or in the guinea pig model and again gave rise to similar severe lung damage. This study seriously questions the safety of vaccines against tuberculosis that target highly conserved heat shock proteins.
authors.affiliation: Mycobacteria Research Laboratories, Departments of Microbiology, Colorado State University, Fort Collins, Colorado, USA.
authors.forename: O C
authors.initials: OC
authors.lastname: Turner
authors.forename: A D
authors.initials: AD
authors.lastname: Roberts
authors.forename: A A
authors.initials: AA
authors.lastname: Frank
authors.forename: S W
authors.initials: SW
authors.lastname: Phalen
authors.forename: D M
authors.initials: DM
authors.lastname: McMurray
authors.forename: J
authors.initials: J
authors.lastname: Content
authors.forename: O
authors.initials: O
authors.lastname: Denis
authors.forename: S
authors.initials: S
authors.lastname: D'Souza
authors.forename: A
authors.initials: A
authors.lastname: Tanghe
authors.forename: K
authors.initials: K
authors.lastname: Huygen
authors.forename: I M
authors.initials: IM
authors.lastname: Orme
mesh_terms: D000818:Animals; D001500:BCG Vaccine / Q000627:therapeutic use*; D001988:Bronchiolitis / Q000473:pathology; D018834:Chaperonin 60 / Q000627:therapeutic use*; D006168:Guinea Pigs; D008168:Lung / Q000473:pathology*; D051379:Mice; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D009336:Necrosis; D018410:Pneumonia, Bacterial / Q000473:pathology; D014397:Tuberculosis, Pulmonary / Q000517:prevention & control*; D014611:Vaccination; D019444:Vaccines, DNA / Q000627:therapeutic use
chemical_list: D001500:BCG Vaccine; D018834:Chaperonin 60; D019444:Vaccines, DNA