Limits...
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

Histopathological pulmonary alterations in a mouse model of drug-sensitive tuberculosis. Representative photomicrographs (hematoxylin and eosin; magnification, 100×) of lung tissue obtained from 16 mice (both alive and dead) in each group 7 weeks post-infection with Mycobacterium tuberculosis H37Rv are shown. (A) Saline group; (B) vector group; (C) Vaccae vaccine group; (D) antigen 85A (Ag85A) DNA vaccine group; (E) alive and (F) dead mice from the Ag85A/6 kDa early secretory antigenic target (ESAT-6) chimeric DNA vaccine plus Ag85A/ESAT-6 chimeric protein boost group.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4940052&req=5

f4-mmr-14-02-1146: Histopathological pulmonary alterations in a mouse model of drug-sensitive tuberculosis. Representative photomicrographs (hematoxylin and eosin; magnification, 100×) of lung tissue obtained from 16 mice (both alive and dead) in each group 7 weeks post-infection with Mycobacterium tuberculosis H37Rv are shown. (A) Saline group; (B) vector group; (C) Vaccae vaccine group; (D) antigen 85A (Ag85A) DNA vaccine group; (E) alive and (F) dead mice from the Ag85A/6 kDa early secretory antigenic target (ESAT-6) chimeric DNA vaccine plus Ag85A/ESAT-6 chimeric protein boost group.

Mentions: Histopathological examination of the lungs demonstrated that in general the vaccinated groups exhibited reduced pathology compared with in the control groups receiving saline or plasmid vector (Fig. 4). At 3 days post-infection, a small scope of consolidation in the local area, scattered small lung lesions, transudate, and hyperaemia in the alveoli were observed (data not shown). At 7 weeks post-infection, more lymphocytes, extensive lung lesions, hyperaemia in the alveoli and damaged structures were observed in the lung sections of the mice in the saline and vector groups. In the Vaccae vaccine group lung lesions were limited, and moderate lymphocyte infiltration and relatively clear and normal structures were observed. In the Ag85A DNA group, lesions were slight with few lymphocytes, and the alveoli exhibited relatively clear and normal structures. Mice in the Ag85A/ESAT-6 chimeric DNA plus Ag85A/ESAT-6 chimeric protein boost group (both alive and dead) all exhibited reduced lesions; however, more transudatory proteins and hyperaemia were detected in the alveoli, and dilated capillary vessels and more lymphocytes surrounding the capillary vessels were observed.


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)

Histopathological pulmonary alterations in a mouse model of drug-sensitive tuberculosis. Representative photomicrographs (hematoxylin and eosin; magnification, 100×) of lung tissue obtained from 16 mice (both alive and dead) in each group 7 weeks post-infection with Mycobacterium tuberculosis H37Rv are shown. (A) Saline group; (B) vector group; (C) Vaccae vaccine group; (D) antigen 85A (Ag85A) DNA vaccine group; (E) alive and (F) dead mice from the Ag85A/6 kDa early secretory antigenic target (ESAT-6) chimeric DNA vaccine plus Ag85A/ESAT-6 chimeric protein boost group.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4940052&req=5

f4-mmr-14-02-1146: Histopathological pulmonary alterations in a mouse model of drug-sensitive tuberculosis. Representative photomicrographs (hematoxylin and eosin; magnification, 100×) of lung tissue obtained from 16 mice (both alive and dead) in each group 7 weeks post-infection with Mycobacterium tuberculosis H37Rv are shown. (A) Saline group; (B) vector group; (C) Vaccae vaccine group; (D) antigen 85A (Ag85A) DNA vaccine group; (E) alive and (F) dead mice from the Ag85A/6 kDa early secretory antigenic target (ESAT-6) chimeric DNA vaccine plus Ag85A/ESAT-6 chimeric protein boost group.
Mentions: Histopathological examination of the lungs demonstrated that in general the vaccinated groups exhibited reduced pathology compared with in the control groups receiving saline or plasmid vector (Fig. 4). At 3 days post-infection, a small scope of consolidation in the local area, scattered small lung lesions, transudate, and hyperaemia in the alveoli were observed (data not shown). At 7 weeks post-infection, more lymphocytes, extensive lung lesions, hyperaemia in the alveoli and damaged structures were observed in the lung sections of the mice in the saline and vector groups. In the Vaccae vaccine group lung lesions were limited, and moderate lymphocyte infiltration and relatively clear and normal structures were observed. In the Ag85A DNA group, lesions were slight with few lymphocytes, and the alveoli exhibited relatively clear and normal structures. Mice in the Ag85A/ESAT-6 chimeric DNA plus Ag85A/ESAT-6 chimeric protein boost group (both alive and dead) all exhibited reduced lesions; however, more transudatory proteins and hyperaemia were detected in the alveoli, and dilated capillary vessels and more lymphocytes surrounding the capillary vessels were observed.

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