Subcutaneous Administration of Modified Vaccinia Virus Ankara Expressing an Ag85B‐ESAT6 Fusion Protein, but Not an Adenovirus‐Based Vaccine, Protects Mice Against Intravenous Challenge with Mycobacterium tuberculosis
Subcutaneous Administration of Modified Vaccinia Virus Ankara Expressing an Ag85B‐ESAT6 Fusion Protein, but Not an Adenovirus‐Based Vaccine, Protects Mice Against Intravenous Challenge with Mycobacterium tuberculosis
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DOI：
10.1111/j.1365-3083.2011.02629.x
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发表时间：
2012-01
影响因子：
3.7
通讯作者：
Qingrui You;Chunlai Jiang;Yongge Wu;Xianghui Yu;Yan Chen;Xue-Zhong Zhang;Wei Wei-Wei;Yaping Wang;Zhijiao Tang;Dehua Jiang;Changyong Wang;X. Meng;X. Zhao;W. Kong
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文献类型：
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作者：
Qingrui You;Chunlai Jiang;Yongge Wu;Xianghui Yu;Yan Chen;Xue-Zhong Zhang;Wei Wei-Wei;Yaping Wang;Zhijiao Tang;Dehua Jiang;Changyong Wang;X. Meng;X. Zhao;W. Kong
基于重组病毒的结核病（TB）疫苗具有很强的免疫原性，并能引发强大的细胞免疫，被认为是理想的候选疫苗。在这里，我们设计了一种基于痘病毒的疫苗MVA 85 B-E6和一种基于腺病毒的疫苗AD 85 B-E6，两者都表达融合蛋白Ag 85 B-ESAT 6。皮下接种AD 85 B-E6可通过CD 4和CD 8 T细胞产生强干扰素（IFN）-γ，并产生CD 8细胞毒性T淋巴细胞活性;这些结果表明，在小鼠中引发了强的1型辅助性T细胞免疫应答，这与接种MVA 85 B-E6诱导的中度应答相反。然而，皮下给予MVA 85 B-E6在肺和脾中产生的保护水平与卡介苗诱导的保护水平相当，而皮下给予AD 85 B-E6在用结核分枝杆菌H37 Rv静脉内攻击BALB/c小鼠后未显示任何保护效力。我们的研究强调，更有效的生物标志物的疫苗效力和更适当的疫苗管理途径是必要的，一个成功的结核病疫苗的发展。
Recombinant virus‐based tuberculosis (TB) vaccines that are strongly immunogenic and elicit robust cellular immunity are considered ideal vaccine candidates. Here, we engineered a poxvirus‐based vaccine, MVA85B‐E6, and an adenovirus‐based vaccine, AD85B‐E6, both of which express the fusion protein Ag85B‐ESAT6. Subcutaneous vaccination of AD85B‐E6 generated strong interferon (IFN)‐γ production by both CD4 and CD8 T cells and CD8 cytotoxic T lymphocyte activity; these results indicate that strong T‐helper type 1 immune responses were elicited in mice, which is in contrast to the moderate responses induced by vaccination with MVA85B‐E6. However, MVA85B‐E6 given subcutaneously led to levels of protection comparable with that induced by the bacillus Calmette–Guérin vaccine in the lungs and spleens, whereas AD85B‐E6 given subcutaneously did not show any protective efficacy after intravenous challenge of BALB/c mice with Mycobacterium tuberculosis H37Rv. Our study emphasizes that more efficient biomarkers for vaccine efficacy and more appropriate routes of vaccine administration are necessary for the development of a successful TB vaccine.