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亚单位疫苗AEC/BC02对化疗后复发的潜伏感染小鼠模型的治疗效果

Therapeutic Effect of Subunit Vaccine AEC/BC02 on Post-Chemotherapy Relapse Using a Latent Infection Murine Model.

作者信息

Lu Jinbiao, Guo Xiaonan, Wang Chunhua, Du Weixin, Shen Xiaobing, Su Cheng, Wu Yongge, Xu Miao

机构信息

National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun 130012, China.

Division of Tuberculosis Vaccine and Allergen Products, Institute of Biological Product Control, National Institutes for Food and Drug Control, Beijing 102629, China.

出版信息

Vaccines (Basel). 2022 May 23;10(5):825. doi: 10.3390/vaccines10050825.

Abstract

Tuberculosis (TB), caused by the human pathogen (), is an infectious disease that presents a major threat to human health. Bacillus Calmette-Guérin (BCG), the only licensed TB vaccine, is ineffective against latent TB infection, necessitating the development of further TB drugs or therapeutic vaccines. Herein, we evaluated the therapeutic effect of a novel subunit vaccine AEC/BC02 after chemotherapy in a spontaneous relapse model. Immunotherapy followed 4 weeks of treatment with isoniazid and rifapentine, and bacterial loads in organs, pathological changes, and adaptive immune characteristics were investigated. The results showed slowly increased bacterial loads in the spleen and lungs of mice inoculated with AEC/BC02 with significantly lower loads than those of the control groups. Pathological scores for the liver, spleen, and lungs decreased accordingly. Moreover, AEC/BC02 induced antigen-specific IFN-γ-secreting or IL-2-secreting cellular immune responses, which decreased with the number of immunizations and times. Obvious Ag85b- and EC-specific IgG were observed in mice following the treatment with AEC/BC02, indicating a significant Th1-biased response. Taken together, these data suggest that AEC/BC02 immunotherapy post-chemotherapy may shorten future TB treatment.

摘要

结核病(TB)由人类病原体(此处原文缺失具体病原体名称)引起,是一种对人类健康构成重大威胁的传染病。卡介苗(BCG)是唯一获得许可的结核病疫苗,对潜伏性结核感染无效,因此需要开发更多的结核病药物或治疗性疫苗。在此,我们在自发复发模型中评估了新型亚单位疫苗AEC/BC02化疗后的治疗效果。在异烟肼和利福喷汀治疗4周后进行免疫治疗,并研究器官中的细菌载量、病理变化和适应性免疫特征。结果显示,接种AEC/BC02的小鼠脾脏和肺部细菌载量缓慢增加,但明显低于对照组。肝脏、脾脏和肺部的病理评分相应降低。此外,AEC/BC02诱导了抗原特异性分泌IFN-γ或分泌IL-2的细胞免疫反应,这种反应随着免疫次数和时间的增加而降低。在用AEC/BC02治疗后的小鼠中观察到明显的Ag85b和EC特异性IgG,表明存在明显的Th1偏向性反应。综上所述,这些数据表明化疗后进行AEC/BC02免疫治疗可能会缩短未来的结核病治疗时间。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/af1b/9145927/92373fb29d6e/vaccines-10-00825-g001.jpg

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