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Infection and Immunity, April 2003, p. 2192-2198, Vol. 71, No. 4
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.4.2192-2198.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Pulmonary Necrosis Resulting from DNA Vaccination against Tuberculosis

Jennifer L. Taylor,1 Oliver C. Turner,1 Randall J. Basaraba,1 John T. Belisle,1 Kris Huygen,2 and Ian M. Orme1*

Mycobacteria Research Laboratories, Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, Colorado 80523,1 Pasteur Institute, Brussels, Belgium2

Received 9 October 2002/ Returned for modification 22 November 2002/ Accepted 6 December 2002

The use of DNA constructs encoding mycobacterial proteins is a promising new approach to vaccination against tuberculosis. A DNA vaccine encoding the hsp60 molecule of Mycobacterium leprae has previously been shown to protect against intravenous infection of mice with Mycobacterium tuberculosis in both the prophylactic and immunotherapeutic modes. It is shown here, however, that this vaccine was not effective in a more realistic aerosol infection model or in a model of latent tuberculosis in the lungs. Moreover, when given in an immunotherapeutic model the immunized mice developed classical Koch reactions characterized by multifocal discrete regions of cellular necrosis throughout the lung granulomas. Similar and equally severe reactions were seen in mice given a vaccine with DNA coding for the Ag85 antigen of M. tuberculosis. This previously unanticipated safety problem indicates that DNA vaccines should be used with caution in individuals who may have already been exposed to tuberculosis.

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

Editor: J. T. Barbieri

Infection and Immunity, April 2003, p. 2192-2198, Vol. 71, No. 4
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.4.2192-2198.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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Copyright © 2003 by the American Society for Microbiology. All rights reserved.