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Ag85A/ESAT-6 chimeric DNA vaccine induces an adverse response in tuberculosis-infected mice.

Liang Y, Bai X, Zhang J, Song J, Yang Y, Yu Q, Li N, Wu X - Mol Med Rep (2016)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: 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.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus

Number of viable bacteria in the (A) lungs and (B) spleens 3 months post-infection with Mycobacterium tuberculosis clinical isolate HB361. (a) Vector group; (b) rifampin (RFP) group; (c) pyrazinamide (PZA) group; (d) antigen 85A (Ag85A) DNA group; (e) Ag85A/6 kDa early secretory antigenic target (ESAT-6) chimeric DNA group; (f) RFP+Ag85A/ESAT-6 chimeric DNA group; (g) PZA + Ag85A/ESAT-6 chimeric DNA group. The bacterial loads present in the Ag85A/ESAT-6 DNA group were determined from the lungs and spleens of 10 dead mice. Data are presented as the mean ± standard deviation. *P<0.05, **P<0.01, ***P<0.001 vs. group a; #P<0.05, ##P<0.01, ###P<0.001 vs. group b; $P<0.05 vs. group c; &&P<0.01 vs. group d and e.
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f1-mmr-14-02-1146: Number of viable bacteria in the (A) lungs and (B) spleens 3 months post-infection with Mycobacterium tuberculosis clinical isolate HB361. (a) Vector group; (b) rifampin (RFP) group; (c) pyrazinamide (PZA) group; (d) antigen 85A (Ag85A) DNA group; (e) Ag85A/6 kDa early secretory antigenic target (ESAT-6) chimeric DNA group; (f) RFP+Ag85A/ESAT-6 chimeric DNA group; (g) PZA + Ag85A/ESAT-6 chimeric DNA group. The bacterial loads present in the Ag85A/ESAT-6 DNA group were determined from the lungs and spleens of 10 dead mice. Data are presented as the mean ± standard deviation. *P<0.05, **P<0.01, ***P<0.001 vs. group a; #P<0.05, ##P<0.01, ###P<0.001 vs. group b; $P<0.05 vs. group c; &&P<0.01 vs. group d and e.

Mentions: A total of 3 months post-infection with HB361, substantial bacterial loads were present in the lungs and spleens of the control mice and the mice treated with RFP, as well as in the lungs and spleens of the mice that succumbed following treatment with Ag85A/ESAT-6 chimeric DNA (Fig. 1). Bacterial loads were ~10-fold lower in the tissues from mice treated with PZA, Ag85A DNA, or Ag85A/ESAT-6 chimeric DNA plus either PZA or RFP.


Ag85A/ESAT-6 chimeric DNA vaccine induces an adverse response in tuberculosis-infected mice.

Liang Y, Bai X, Zhang J, Song J, Yang Y, Yu Q, Li N, Wu X - Mol Med Rep (2016)

Number of viable bacteria in the (A) lungs and (B) spleens 3 months post-infection with Mycobacterium tuberculosis clinical isolate HB361. (a) Vector group; (b) rifampin (RFP) group; (c) pyrazinamide (PZA) group; (d) antigen 85A (Ag85A) DNA group; (e) Ag85A/6 kDa early secretory antigenic target (ESAT-6) chimeric DNA group; (f) RFP+Ag85A/ESAT-6 chimeric DNA group; (g) PZA + Ag85A/ESAT-6 chimeric DNA group. The bacterial loads present in the Ag85A/ESAT-6 DNA group were determined from the lungs and spleens of 10 dead mice. Data are presented as the mean ± standard deviation. *P<0.05, **P<0.01, ***P<0.001 vs. group a; #P<0.05, ##P<0.01, ###P<0.001 vs. group b; $P<0.05 vs. group c; &&P<0.01 vs. group d and e.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4940052&req=5

f1-mmr-14-02-1146: Number of viable bacteria in the (A) lungs and (B) spleens 3 months post-infection with Mycobacterium tuberculosis clinical isolate HB361. (a) Vector group; (b) rifampin (RFP) group; (c) pyrazinamide (PZA) group; (d) antigen 85A (Ag85A) DNA group; (e) Ag85A/6 kDa early secretory antigenic target (ESAT-6) chimeric DNA group; (f) RFP+Ag85A/ESAT-6 chimeric DNA group; (g) PZA + Ag85A/ESAT-6 chimeric DNA group. The bacterial loads present in the Ag85A/ESAT-6 DNA group were determined from the lungs and spleens of 10 dead mice. Data are presented as the mean ± standard deviation. *P<0.05, **P<0.01, ***P<0.001 vs. group a; #P<0.05, ##P<0.01, ###P<0.001 vs. group b; $P<0.05 vs. group c; &&P<0.01 vs. group d and e.
Mentions: A total of 3 months post-infection with HB361, substantial bacterial loads were present in the lungs and spleens of the control mice and the mice treated with RFP, as well as in the lungs and spleens of the mice that succumbed following treatment with Ag85A/ESAT-6 chimeric DNA (Fig. 1). Bacterial loads were ~10-fold lower in the tissues from mice treated with PZA, Ag85A DNA, or Ag85A/ESAT-6 chimeric DNA plus either PZA or RFP.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: 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.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus