Protective effect of DNA vaccine during chemotherapy on reactivation and reinfection of Mycobacterium tuberculosis

S-J Ha1,4, B-Y Jeon2,4, J-I Youn1, S-C Kim2, S-N Cho2,3,4 and Y-C Sung1,4

1Division of Molecular and Life Sciences, Postech Biotech Center, Pohang University of Science & Technology, Pohang, Republic of Korea; 2Department of Microbiology and Brain Korea 21 Project for Medical Sciences, Yonsei University College of Medicine, Seoul, Republic of Korea; and 3The International Vaccine Institute, Seoul, Republic of Korea

Active disease of tuberculosis (TB) can be developed decades later by either a relapse of the initial infection (endogenous reactivation) or by an entrance of the secondary infection (exogenous reinfection), since the current chemotherapy cannot lead to complete elimination of tuberculosis. Although the immunotherapeutic approaches in conjunction with conventional chemotherapy were tried to prevent TB growth via boosting the immune system, their therapeutic effects are still controversial. Here, we found that TB DNA vaccination completely blocked tuberculosis reactivation and significantly prevented from the secondary infection when chemotherapy was combined simultaneously. In particular, double-gene DNA vaccine composed of Ag85A and PstS-3 genes could reduce bacteria growth better than single-gene DNA vaccine after a secondary reinfection, indicating a correlation between the breadth of Th1 IFN-g response and the efficacy of the protection from reinfection. Thus, we propose that multigene TB DNA immunotherapy including Ag85A and PstS-3 genes during the period of chemotherapy could benefit patients undergoing TB chemotherapy in prevention from exogenous reinfection as well as endogenous reactivation.

Gene Therapy advance online publication, 3 February 2005; doi:10.1038/

Keywords: Mycobacterium tuberculosis; double-gene DNA vaccine; chemotherapy; Ag85A; PstS-3

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