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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

Histopathological pulmonary alterations in a mouse model of multi-drug-resistant tuberculosis. Representative photomicrographs (hematoxylin and eosin; magnification, 200×) of lung tissues obtained from the mice of each group that were still alive 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) RFP + Ag85A/6 kDa early secretory antigenic target (ESAT-6) chimeric DNA group; (F) PZA + Ag85A/ESAT-6 chimeric DNA group. Ag85A/ESAT-6 chimeric DNA group is not shown.
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f2-mmr-14-02-1146: Histopathological pulmonary alterations in a mouse model of multi-drug-resistant tuberculosis. Representative photomicrographs (hematoxylin and eosin; magnification, 200×) of lung tissues obtained from the mice of each group that were still alive 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) RFP + Ag85A/6 kDa early secretory antigenic target (ESAT-6) chimeric DNA group; (F) PZA + Ag85A/ESAT-6 chimeric DNA group. Ag85A/ESAT-6 chimeric DNA group is not shown.

Mentions: Microscopic examination of the lung sections from mice in the plasmid vector and RFP-treated groups detected little alteration from the expected histopathological characteristics of murine tuberculosis. Mice in the other groups exhibited more foam cells and multi-nucleated giant cells, but fewer lymphocytes in the lung sections, and the alveolar profiles detected relatively clear and normal structures. The percentage of the total section area that was deemed pathological was 100, 90, 65–75, 30–40, 50–60 and 50–60% in the plasmid vector group, RFP group, PZA group, Ag85A DNA group, RFP + Ag85A/ESAT-6 chimeric DNA group and PZA + Ag85A/ESAT-6 chimeric DNA group, respectively. Representative histopathological images of each group are presented in Fig. 2.


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 multi-drug-resistant tuberculosis. Representative photomicrographs (hematoxylin and eosin; magnification, 200×) of lung tissues obtained from the mice of each group that were still alive 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) RFP + Ag85A/6 kDa early secretory antigenic target (ESAT-6) chimeric DNA group; (F) PZA + Ag85A/ESAT-6 chimeric DNA group. Ag85A/ESAT-6 chimeric DNA group is not shown.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f2-mmr-14-02-1146: Histopathological pulmonary alterations in a mouse model of multi-drug-resistant tuberculosis. Representative photomicrographs (hematoxylin and eosin; magnification, 200×) of lung tissues obtained from the mice of each group that were still alive 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) RFP + Ag85A/6 kDa early secretory antigenic target (ESAT-6) chimeric DNA group; (F) PZA + Ag85A/ESAT-6 chimeric DNA group. Ag85A/ESAT-6 chimeric DNA group is not shown.
Mentions: Microscopic examination of the lung sections from mice in the plasmid vector and RFP-treated groups detected little alteration from the expected histopathological characteristics of murine tuberculosis. Mice in the other groups exhibited more foam cells and multi-nucleated giant cells, but fewer lymphocytes in the lung sections, and the alveolar profiles detected relatively clear and normal structures. The percentage of the total section area that was deemed pathological was 100, 90, 65–75, 30–40, 50–60 and 50–60% in the plasmid vector group, RFP group, PZA group, Ag85A DNA group, RFP + Ag85A/ESAT-6 chimeric DNA group and PZA + Ag85A/ESAT-6 chimeric DNA group, respectively. Representative histopathological images of each group are presented in Fig. 2.

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