Ag85A/ESAT-6 chimeric DNA vaccine induces an adverse response in tuberculosis-infected mice.
The Mycobacterium tuberculosis (M. tb) antigens encoded by the 6 kDa early secretory antigenic target (esat-6) and antigen 85A (ag85a) genes are known to exert protective effects against tuberculosis in animal models. In addition, these antigens represent vaccine components that were tested in early human clinical trials. In the present study, a chimeric DNA vaccine was constructed that contained two copies of the esat‑6 gene inserted into the ag85a gene from M. tb. BALB/c mice were treated with this chimeric vaccine following infection with either M. tb H37Rv or a clinical multi-drug-resistant tuberculosis isolate. Treatment of both groups of mice with the chimeric vaccine resulted in accelerated mortality. These findings are in contrast with previous results, which indicated that DNA vaccines expressing the individual antigens were either beneficial or at least not harmful. The results of the present study suggested that the ESAT-6 antigen is not suitable for inclusion in therapeutic vaccines.
Army Tuberculosis Prevention and Control Key Laboratory, Beijing Key Laboratory of New Techniques of Tuberculosis Diagnosis and Treatment, Institute of Tuberculosis Research, The 309th Hospital of Chinese PLA, Beijing 100091, P.R. China.
Yan
Y
Liang
Army Tuberculosis Prevention and Control Key Laboratory, Beijing Key Laboratory of New Techniques of Tuberculosis Diagnosis and Treatment, Institute of Tuberculosis Research, The 309th Hospital of Chinese PLA, Beijing 100091, P.R. China.
Xuejuang
X
Bai
Army Tuberculosis Prevention and Control Key Laboratory, Beijing Key Laboratory of New Techniques of Tuberculosis Diagnosis and Treatment, Institute of Tuberculosis Research, The 309th Hospital of Chinese PLA, Beijing 100091, P.R. China.
Junxian
J
Zhang
Army Tuberculosis Prevention and Control Key Laboratory, Beijing Key Laboratory of New Techniques of Tuberculosis Diagnosis and Treatment, Institute of Tuberculosis Research, The 309th Hospital of Chinese PLA, Beijing 100091, P.R. China.
Jingying
J
Song
Army Tuberculosis Prevention and Control Key Laboratory, Beijing Key Laboratory of New Techniques of Tuberculosis Diagnosis and Treatment, Institute of Tuberculosis Research, The 309th Hospital of Chinese PLA, Beijing 100091, P.R. China.
Yourong
Y
Yang
Army Tuberculosis Prevention and Control Key Laboratory, Beijing Key Laboratory of New Techniques of Tuberculosis Diagnosis and Treatment, Institute of Tuberculosis Research, The 309th Hospital of Chinese PLA, Beijing 100091, P.R. China.
Qi
Q
Yu
Army Tuberculosis Prevention and Control Key Laboratory, Beijing Key Laboratory of New Techniques of Tuberculosis Diagnosis and Treatment, Institute of Tuberculosis Research, The 309th Hospital of Chinese PLA, Beijing 100091, P.R. China.
Ning
N
Li
Army Tuberculosis Prevention and Control Key Laboratory, Beijing Key Laboratory of New Techniques of Tuberculosis Diagnosis and Treatment, Institute of Tuberculosis Research, The 309th Hospital of Chinese PLA, Beijing 100091, P.R. China.
Xueqiong
X
Wu
D000217:Acyltransferases / Q000235:genetics / Q000276:immunology*; D000818:Animals; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology*; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D051379:Mice; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology*; D014376:Tuberculosis / Q000276:immunology* / Q000382:microbiology / Q000401:mortality / Q000517:prevention & control; D032581:Tuberculosis Vaccines / Q000235:genetics / Q000276:immunology*; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology*
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C093276:ESAT-6 protein, Mycobacterium tuberculosis; D011993:Recombinant Fusion Proteins; D032581:Tuberculosis Vaccines; D019444:Vaccines, DNA; D000217:Acyltransferases; C121433:antigen 85B, Mycobacterium tuberculosis