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重组卡介苗共表达 Ag85b、CFP10 和白细胞介素-12 可有效预防结核分枝杆菌感染。

Recombinant bacille Calmette-Guerin coexpressing Ag85b, CFP10, and interleukin-12 elicits effective protection against Mycobacterium tuberculosis.

机构信息

National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan, Miaoli, Taiwan.

National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan, Miaoli, Taiwan.

出版信息

J Microbiol Immunol Infect. 2017 Feb;50(1):90-96. doi: 10.1016/j.jmii.2014.11.019. Epub 2014 Dec 11.

DOI:10.1016/j.jmii.2014.11.019
PMID:25732698
Abstract

BACKGROUND

The tuberculosis (TB) pandemic remains a leading cause of human morbidity and mortality, despite widespread use of the only licensed anti-TB vaccine, bacille Calmette-Guerin (BCG). The protective efficacy of BCG in preventing pulmonary TB is highly variable; therefore, an effective new vaccine is urgently required.

METHODS

In the present study, we assessed the ability of novel recombinant BCG vaccine (rBCG) against Mycobacterium tuberculosis by using modern immunological methods.

RESULTS

Enzyme-linked immunospot assays demonstrated that the rBCG vaccine, which coexpresses two mycobacterial antigens (Ag85B and CFP10) and human interleukin (IL)-12 (rBCG2) elicits greater interferon-γ (IFN-γ) release in the mouse lung and spleen, compared to the parental BCG. In addition, rBCG2 triggers a Th1-polarized response. Our results also showed that rBCG2 vaccination significantly limits M. tuberculosis H37Rv multiplication in macrophages. The rBCG2 vaccine surprisingly induces significantly higher tumor necrosis factor-α (TNF-α) production by peripheral blood mononuclear cells that were exposed to a nonmycobacterial stimulus, compared to the parental BCG.

CONCLUSION

In this study, we demonstrated that the novel rBCG2 vaccine may be a promising candidate vaccine against M. tuberculosis infection.

摘要

背景

尽管广泛使用了唯一获得许可的抗结核疫苗卡介苗(BCG),但结核病(TB)仍然是导致人类发病率和死亡率的主要原因。BCG 预防肺结核的保护效果差异很大;因此,迫切需要一种有效的新型疫苗。

方法

在本研究中,我们使用现代免疫学方法评估了新型重组卡介苗(rBCG)疫苗针对结核分枝杆菌的能力。

结果

酶联免疫斑点分析显示,与亲本 BCG 相比,共表达两种分枝杆菌抗原(Ag85B 和 CFP10)和人白细胞介素(IL)-12 的 rBCG2 疫苗在小鼠肺部和脾脏中引起更大的干扰素-γ(IFN-γ)释放。此外,rBCG2 引发 Th1 极化反应。我们的研究结果还表明,rBCG2 疫苗接种可显著限制巨噬细胞中结核分枝杆菌 H37Rv 的繁殖。与亲本 BCG 相比,rBCG2 疫苗出乎意料地诱导了对外周血单个核细胞暴露于非分枝杆菌刺激物时产生的肿瘤坏死因子-α(TNF-α)的产生显著增加。

结论

在这项研究中,我们证明了新型 rBCG2 疫苗可能是一种有前途的抗结核分枝杆菌感染候选疫苗。

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