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Infection and Immunity, June 2000, p. 3674-3679, Vol. 68, No. 6
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

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

Oliver C. Turner,1 Alan D. Roberts,1 Anthony A. Frank,2 Susan W. Phalen,3 David M. McMurray,3 Jean Content,4 Olivier Denis,4 Sushila D'Souza,4 Audrey Tanghe,4 Kris Huygen,4 and Ian M. Orme1,*

Mycobacteria Research Laboratories, Departments of Microbiology1 and Pathology,2 Colorado State University, Fort Collins, Colorado; Department of Medical Microbiology and Immunology, Texas A&M University, College Station, Texas3; and Mycobacterial Immunology, Pasteur Institute, Brussels, Belgium4

Received 22 December 1999/Returned for modification 22 February 2000/Accepted 9 March 2000

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.

* Corresponding author. Mailing address: Department of Microbiology, Colorado State University, Fort Collins, CO 80523. Phone: (970) 491-5777. Fax: (970) 491-5125. E-mail: iorme{at}lamar.colostate.edu.

Infection and Immunity, June 2000, p. 3674-3679, Vol. 68, No. 6
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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