Pulmonary necrosis resulting from DNA vaccination against tuberculosis.
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.
Taylor
Jennifer L
JL
Mycobacteria Research Laboratories, Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, CO 80523, USA.
Turner
Oliver C
OC
Basaraba
Randall J
RJ
Belisle
John T
JT
Huygen
Kris
K
Orme
Ian M
IM
D000818:Animals; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology; D018834:Chaperonin 60 / Q000235:genetics / Q000276:immunology; D005260:Female; D008168:Lung / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009166:Mycobacterium leprae / Q000235:genetics / Q000276:immunology; D009169:Mycobacterium tuberculosis / Q000472:pathogenicity*; D009336:Necrosis; D013047:Specific Pathogen-Free Organisms; D032581:Tuberculosis Vaccines / Q000009:adverse effects* / Q000627:therapeutic use; D014397:Tuberculosis, Pulmonary / Q000473:pathology / Q000517:prevention & control* / Q000628:therapy; D014611:Vaccination; D019444:Vaccines, DNA / Q000009:adverse effects* / Q000627:therapeutic use
D000942:Antigens, Bacterial; D018834:Chaperonin 60; D032581:Tuberculosis Vaccines; D019444:Vaccines, DNA; C072681:Mycobacterium tuberculosis antigens