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Therapeutic effect of DNA vaccines combined with chemotherapy in a latent infection model after aerosol infection of mice with Mycobacterium tuberculosis

 S-J Ha  ;  B-Y Jeon  ;  S-N Cho  ;  Y-C Sung  ;  M-K Song  ;  D-J Kim  ;  S-C Kim 
 GENE THERAPY, Vol.10(18) : 1592-1599, 2003 
Journal Title
Issue Date
Animals ; Antigens, Bacterial/genetics* ; Antitubercular Agents/therapeutic use ; Colony Count, Microbial ; Female ; Genetic Therapy/methods* ; Interferon-gamma/immunology ; Interleukin-12/genetics ; Mice ; Mice, Inbred C57BL ; Models, Animal ; Mycobacterium tuberculosis/immunology* ; Recurrence ; Tuberculosis/drug therapy ; Tuberculosis/prevention & control* ; Tuberculosis/therapy ; Vaccines, DNA/administration & dosage*
Mycobacterium tuberculosis ; DNA vaccine ; chemotherapy ; Ag85A ; IL-12N220L
The prevention of Mycobacterium tuberculosis (M. tuberculosis) reactivation would greatly reduce the incidence of the disease, particularly among the elderly. Here, we evaluated the efficacy of DNA vaccine in combination with a conventional TB chemotherapy on the prevention of M. tuberculosis reactivation. Mice were treated with isoniazid and pyrazinamide for 3 months from 4 weeks after aerosol infection with M. tuberculosis H37Rv. During this period of chemotherapy, DNA immunization was performed three times monthly with an antigen 85A (Ag85A) DNA or an IL-12 mutant (IL-12N220L) DNA, which is known to lead to a reduction in the secretion of the p40 subunit, but not of a bioactive IL-12p70. The reactivation of M. tuberculosis was dramatically reduced in mice treated with either Ag85A DNA (P<0.01) or IL-12N220L DNA (P<0.05) in combination with chemotherapy, compared with control mice receiving only chemotherapy. Ag85A DNA vaccine showed higher IFN-gamma responses to Ag85A protein, but a lower response to culture filtrate than IL-12N220L DNA vaccine. In addition, Ag85A DNA vaccine prevented the reactivation of M. tuberculosis more efficiently than IL-12N220L DNA vaccine, indicating that Ag85A-specific IFN-gamma response might correlate with M. tuberculosis control. This study suggests that immunotherapy using Ag85A or IL-12N220L DNA vaccine combined with conventional chemotherapy might be effective clinically for the prevention of tuberculosis reactivation and may offer a more effective cure for humans than chemotherapy alone.
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5. Research Institutes (연구소) > Institute for Immunology and Immunological Disease (면역질환연구소) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Microbiology (미생물학교실) > 1. Journal Papers
Yonsei Authors
Jeon, Bo Young(전보영)
Cho, Sang Nae(조상래)
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