Xu Ying, Yang Enzhuo, Wang Jianguang, Li Rui, Li Guanghua, Liu Guoyuan, Song Na, Huang Qi, Kong Cong, Wang Honghai
State Key Laboratory of Genetic Engineering, School of Life Science, Fudan University, Shanghai, China.
Immunology. 2014 Oct;143(2):277-86. doi: 10.1111/imm.12308.
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-Guérin (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.
为防止结核病在全球传播，迫切需要更有效的疫苗和接种策略。由于卡介苗（BCG）在保护儿童免受粟粒性和结核性脑膜炎方面取得成功，大多数人都接种过卡介苗；因此，增强卡介苗引发的免疫力可能是未来疫苗策略的关键组成部分。在本研究中，我们比较了表达抗原Ag85B和Rv3425的基于DNA、蛋白质和慢病毒载体的疫苗在增强卡介苗对C57BL/6小鼠抗结核分枝杆菌免疫和保护作用方面的能力。我们的结果表明，与基于DNA和蛋白质的疫苗相比，用表达抗原Ag85B和Rv3425的慢病毒载体进行初免-加强卡介苗接种可显著增强免疫反应，包括1型辅助性T细胞和CD8(+)细胞毒性T淋巴细胞反应。然而，慢病毒载体疫苗和基于DNA的疫苗大大提高了卡介苗对结核分枝杆菌的保护效力，表现为体重没有减轻，肺部细菌载量显著降低，组织学损伤减轻。我们的研究表明，使用含有抗原Ag85B和Rv3425的慢病毒或DNA疫苗来加强卡介苗接种，是合理设计高效抗结核疫苗策略的一个不错选择。
