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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 lungs at 7 weeks post-infection with Mycobacterium tuberculosis H37Rv. (a) Saline group; (b) vector group; (c) Vaccae vaccine group; (d) Ag85A DNA vaccine group; (e) Ag85A/6 kDa early secretory antigenic target (ESAT-6) chimeric DNA vaccine plus Ag85A/ESAT-6 chimeric protein boost group. Data are presented as the mean ± standard deviation. *P<0.001 vs. groups a, b, c and d.
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f3-mmr-14-02-1146: Number of viable bacteria in the lungs at 7 weeks post-infection with Mycobacterium tuberculosis H37Rv. (a) Saline group; (b) vector group; (c) Vaccae vaccine group; (d) Ag85A DNA vaccine group; (e) Ag85A/6 kDa early secretory antigenic target (ESAT-6) chimeric DNA vaccine plus Ag85A/ESAT-6 chimeric protein boost group. Data are presented as the mean ± standard deviation. *P<0.001 vs. groups a, b, c and d.

Mentions: The log10 bacterial load in the lungs was determined at 3 days (data not shown) or 7 weeks post-infection (Fig. 3). At 3 days post-infection with H37Rv (prior to treatment), the log10 bacterial load in the lungs from 10 mice was 7.04. At 7 weeks post-infection, compared with the CFU in the control groups treated with saline (7.31) or empty DNA vaccine vector (7.20), treatment with Vaccae had no effect on CFU (7.21). The load was slightly but significantly lower (6.93; P<0.05) following treatment with Ag85A DNA, and was almost 2 log10 lower in the mice that succumbed following treatment with Ag85A/ESAT-6 chimeric DNA plus Ag85A/ESAT-6 chimeric protein boost (5.37 log10; P< 0. 0 01).


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 lungs at 7 weeks post-infection with Mycobacterium tuberculosis H37Rv. (a) Saline group; (b) vector group; (c) Vaccae vaccine group; (d) Ag85A DNA vaccine group; (e) Ag85A/6 kDa early secretory antigenic target (ESAT-6) chimeric DNA vaccine plus Ag85A/ESAT-6 chimeric protein boost group. Data are presented as the mean ± standard deviation. *P<0.001 vs. groups a, b, c and d.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4940052&req=5

f3-mmr-14-02-1146: Number of viable bacteria in the lungs at 7 weeks post-infection with Mycobacterium tuberculosis H37Rv. (a) Saline group; (b) vector group; (c) Vaccae vaccine group; (d) Ag85A DNA vaccine group; (e) Ag85A/6 kDa early secretory antigenic target (ESAT-6) chimeric DNA vaccine plus Ag85A/ESAT-6 chimeric protein boost group. Data are presented as the mean ± standard deviation. *P<0.001 vs. groups a, b, c and d.
Mentions: The log10 bacterial load in the lungs was determined at 3 days (data not shown) or 7 weeks post-infection (Fig. 3). At 3 days post-infection with H37Rv (prior to treatment), the log10 bacterial load in the lungs from 10 mice was 7.04. At 7 weeks post-infection, compared with the CFU in the control groups treated with saline (7.31) or empty DNA vaccine vector (7.20), treatment with Vaccae had no effect on CFU (7.21). The load was slightly but significantly lower (6.93; P<0.05) following treatment with Ag85A DNA, and was almost 2 log10 lower in the mice that succumbed following treatment with Ag85A/ESAT-6 chimeric DNA plus Ag85A/ESAT-6 chimeric protein boost (5.37 log10; P< 0. 0 01).

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