Mechanisms of ag85a/b DNA vaccine conferred immunotherapy and recovery from Mycobacterium tuberculosis‐induced injury
Abstract Our previous research developed a novel tuberculosis (TB) DNA vaccine ag85a/b that showed a significant therapeutic effect on the mouse tuberculosis model by intramuscular injection (IM) and electroporation (EP). However, the action mechanisms between these two vaccine immunization methods...
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Wiley
2023-05-01
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| Series: | Immunity, Inflammation and Disease |
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| Online Access: | https://doi.org/10.1002/iid3.854 |
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| author | Nan Wang Yan Liang Qianqian Ma Jie Mi Yong Xue Yourong Yang Lan Wang Xueqiong Wu |
| author_facet | Nan Wang Yan Liang Qianqian Ma Jie Mi Yong Xue Yourong Yang Lan Wang Xueqiong Wu |
| author_sort | Nan Wang |
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| description | Abstract Our previous research developed a novel tuberculosis (TB) DNA vaccine ag85a/b that showed a significant therapeutic effect on the mouse tuberculosis model by intramuscular injection (IM) and electroporation (EP). However, the action mechanisms between these two vaccine immunization methods remain unclear. In a previous study, 96 Mycobacterium tuberculosis (MTB) H37Rv‐infected BALB/c mice were treated with phosphate‐buffered saline, 10, 50, 100, and 200 μg ag85a/b DNA vaccine delivered by IM and EP three times at 2‐week intervals, respectively. In this study, peripheral blood mononuclear cells (PBMCs) from three mice in each group were isolated to extract total RNA. The gene expression profiles were analyzed using gene microarray technology to obtain differentially expressed (DE) genes. Finally, DE genes were validated by real‐time reverse transcription‐quantitive polymerase chain reaction and the GEO database. After MTB infection, most of the upregulated DE genes were related to the digestion and absorption of nutrients or neuroendocrine (such as Iapp, Scg2, Chga, Amy2a5), and most of the downregulated DE genes were related to cellular structural and functional proteins, especially the structure and function proteins of the alveolar epithelial cell (such as Sftpc, Sftpd, Pdpn). Most of the abnormally upregulated or downregulated DE genes in the TB model group were recovered in the 100 and 200 μg ag85a/b DNA IM groups and four DNA EP groups. The pancreatic secretion pathway downregulated and the Rap1 signal pathway upregulated had particularly significant changes during the immunotherapy of the ag85a/b DNA vaccine on the mouse TB model. The action targets and mechanisms of IM and EP are highly consistent. Tuberculosis infection causes rapid catabolism and slow anabolism in mice. For the first time, we found that the effective dose of the ag85a/b DNA vaccine immunized whether by IM or EP could significantly up‐regulate immune‐related pathways and recover the metabolic disorder and the injury caused by MTB. |
| format | Article |
| id | doaj-art-5076c20b3b424c24bd9e708046931433 |
| institution | OA Journals |
| issn | 2050-4527 |
| language | English |
| publishDate | 2023-05-01 |
| publisher | Wiley |
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| series | Immunity, Inflammation and Disease |
| spelling | doaj-art-5076c20b3b424c24bd9e7080469314332025-08-20T02:15:41ZengWileyImmunity, Inflammation and Disease2050-45272023-05-01115n/an/a10.1002/iid3.854Mechanisms of ag85a/b DNA vaccine conferred immunotherapy and recovery from Mycobacterium tuberculosis‐induced injuryNan Wang0Yan Liang1Qianqian Ma2Jie Mi3Yong Xue4Yourong Yang5Lan Wang6Xueqiong Wu7Tuberculosis Prevention and Control Key Laboratory, Beijing Key Laboratory of New Techniques of Tuberculosis Diagnosis and Treatment, Senior Department of Tuberculosis, The Eighth Medical Center of PLA General Hospital PLA General Hospital Beijing ChinaTuberculosis Prevention and Control Key Laboratory, Beijing Key Laboratory of New Techniques of Tuberculosis Diagnosis and Treatment, Senior Department of Tuberculosis, The Eighth Medical Center of PLA General Hospital PLA General Hospital Beijing ChinaTuberculosis Prevention and Control Key Laboratory, Beijing Key Laboratory of New Techniques of Tuberculosis Diagnosis and Treatment, Senior Department of Tuberculosis, The Eighth Medical Center of PLA General Hospital PLA General Hospital Beijing ChinaTuberculosis Prevention and Control Key Laboratory, Beijing Key Laboratory of New Techniques of Tuberculosis Diagnosis and Treatment, Senior Department of Tuberculosis, The Eighth Medical Center of PLA General Hospital PLA General Hospital Beijing ChinaTuberculosis Prevention and Control Key Laboratory, Beijing Key Laboratory of New Techniques of Tuberculosis Diagnosis and Treatment, Senior Department of Tuberculosis, The Eighth Medical Center of PLA General Hospital PLA General Hospital Beijing ChinaTuberculosis Prevention and Control Key Laboratory, Beijing Key Laboratory of New Techniques of Tuberculosis Diagnosis and Treatment, Senior Department of Tuberculosis, The Eighth Medical Center of PLA General Hospital PLA General Hospital Beijing ChinaTuberculosis Prevention and Control Key Laboratory, Beijing Key Laboratory of New Techniques of Tuberculosis Diagnosis and Treatment, Senior Department of Tuberculosis, The Eighth Medical Center of PLA General Hospital PLA General Hospital Beijing ChinaTuberculosis Prevention and Control Key Laboratory, Beijing Key Laboratory of New Techniques of Tuberculosis Diagnosis and Treatment, Senior Department of Tuberculosis, The Eighth Medical Center of PLA General Hospital PLA General Hospital Beijing ChinaAbstract Our previous research developed a novel tuberculosis (TB) DNA vaccine ag85a/b that showed a significant therapeutic effect on the mouse tuberculosis model by intramuscular injection (IM) and electroporation (EP). However, the action mechanisms between these two vaccine immunization methods remain unclear. In a previous study, 96 Mycobacterium tuberculosis (MTB) H37Rv‐infected BALB/c mice were treated with phosphate‐buffered saline, 10, 50, 100, and 200 μg ag85a/b DNA vaccine delivered by IM and EP three times at 2‐week intervals, respectively. In this study, peripheral blood mononuclear cells (PBMCs) from three mice in each group were isolated to extract total RNA. The gene expression profiles were analyzed using gene microarray technology to obtain differentially expressed (DE) genes. Finally, DE genes were validated by real‐time reverse transcription‐quantitive polymerase chain reaction and the GEO database. After MTB infection, most of the upregulated DE genes were related to the digestion and absorption of nutrients or neuroendocrine (such as Iapp, Scg2, Chga, Amy2a5), and most of the downregulated DE genes were related to cellular structural and functional proteins, especially the structure and function proteins of the alveolar epithelial cell (such as Sftpc, Sftpd, Pdpn). Most of the abnormally upregulated or downregulated DE genes in the TB model group were recovered in the 100 and 200 μg ag85a/b DNA IM groups and four DNA EP groups. The pancreatic secretion pathway downregulated and the Rap1 signal pathway upregulated had particularly significant changes during the immunotherapy of the ag85a/b DNA vaccine on the mouse TB model. The action targets and mechanisms of IM and EP are highly consistent. Tuberculosis infection causes rapid catabolism and slow anabolism in mice. For the first time, we found that the effective dose of the ag85a/b DNA vaccine immunized whether by IM or EP could significantly up‐regulate immune‐related pathways and recover the metabolic disorder and the injury caused by MTB.https://doi.org/10.1002/iid3.854ag85a/b DNADNA vaccineimmunotherapyMycobacterium tuberculosistranscriptome |
| spellingShingle | Nan Wang Yan Liang Qianqian Ma Jie Mi Yong Xue Yourong Yang Lan Wang Xueqiong Wu Mechanisms of ag85a/b DNA vaccine conferred immunotherapy and recovery from Mycobacterium tuberculosis‐induced injury Immunity, Inflammation and Disease ag85a/b DNA DNA vaccine immunotherapy Mycobacterium tuberculosis transcriptome |
| title | Mechanisms of ag85a/b DNA vaccine conferred immunotherapy and recovery from Mycobacterium tuberculosis‐induced injury |
| title_full | Mechanisms of ag85a/b DNA vaccine conferred immunotherapy and recovery from Mycobacterium tuberculosis‐induced injury |
| title_fullStr | Mechanisms of ag85a/b DNA vaccine conferred immunotherapy and recovery from Mycobacterium tuberculosis‐induced injury |
| title_full_unstemmed | Mechanisms of ag85a/b DNA vaccine conferred immunotherapy and recovery from Mycobacterium tuberculosis‐induced injury |
| title_short | Mechanisms of ag85a/b DNA vaccine conferred immunotherapy and recovery from Mycobacterium tuberculosis‐induced injury |
| title_sort | mechanisms of ag85a b dna vaccine conferred immunotherapy and recovery from mycobacterium tuberculosis induced injury |
| topic | ag85a/b DNA DNA vaccine immunotherapy Mycobacterium tuberculosis transcriptome |
| url | https://doi.org/10.1002/iid3.854 |
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