Prime-boost bacillus Calmette-Guerin vaccination with lentivirus-vectored and DNA-based vaccines expressing antigens Ag85B and Rv3425 improves protective efficacy against Mycobacterium tuberculosis in mice
Prime-boost bacillus Calmette-Guerin vaccination with lentivirus-vectored and DNA-based vaccines expressing antigens Ag85B and Rv3425 improves protective efficacy against Mycobacterium tuberculosis in mice
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DOI：
10.1111/imm.12308
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发表时间：
2014-10-01
期刊：
影响因子：
6.4
通讯作者：
Wang, Honghai
中科院分区：
文献类型：
--
作者：
Xu, Ying;Yang, Enzhuo;Wang, Honghai
为了防止结核病在全球传播，迫切需要更有效的疫苗和疫苗接种战略。由于卡介苗（BCG）在保护儿童免受军性结核病和脑膜炎方面取得了成功，大多数人将接种卡介苗疫苗；因此，增强bcg引发的免疫力可能是未来疫苗策略的关键组成部分。在这项研究中，我们比较了表达抗原Ag85B和Rv3425的DNA、蛋白质和慢病毒载体疫苗在C57BL/6小鼠中增强BCG免疫和保护结核分枝杆菌的能力。我们的研究结果表明，与基于dna和蛋白质的疫苗相比，用表达抗原Ag85B和Rv3425的慢病毒载体接种卡介苗可显著增强免疫应答，包括T辅助型1和CD8（+）细胞毒性T淋巴细胞应答。然而，慢病毒载体和基于dna的疫苗大大提高了卡介苗对结核分枝杆菌的保护功效，这表明体重没有减轻，并且显著减少了肺部的细菌负荷和组织学损伤。我们的研究表明，使用含有抗原Ag85B和Rv3425的慢病毒或DNA疫苗来增强卡介苗是合理设计有效的结核病疫苗接种策略的良好选择。
To prevent the global spread of tuberculosis (TB), more effective vaccines and vaccination strategies are urgently needed. As a result of the success of bacillus Calmette-Guerin (BCG) in protecting children against miliary and meningeal TB, the majority of individuals will have been vaccinated with BCG; hence, boosting BCG-primed immunity will probably be a key component of future vaccine strategies. In this study, we compared the ability of DNA-, protein-and lentiviral vector-based vaccines that express the antigens Ag85B and Rv3425 to boost the effects of BCG in the context of immunity and protection against Mycobacterium tuberculosis in C57BL/6 mice. Our results demonstrated that prime-boost BCG vaccination with a lentiviral vector expressing the antigens Ag85B and Rv3425 significantly enhanced immune responses, including T helper type 1 and CD8(+) cytotoxic T lymphocyte responses, compared with DNA-and protein-based vaccines. However, lentivirus-vectored and DNA-based vaccines greatly improved the protective efficacy of BCG against M. tuberculosis, as indicated by a lack of weight loss and significantly reduced bacterial loads and histological damage in the lung. Our study suggests that the use of lentiviral or DNA vaccines containing the antigens Ag85B and Rv3425 to boost BCG is a good choice for the rational design of an efficient vaccination strategy against TB.