Qie Y Q, Wang J L, Zhu B D, Xu Y, Wang Q Z, Chen J Z, Wang H H
Institute of Genetics, School of Life Science, Fudan University, Shanghai, China.
Scand J Immunol. 2008 Feb;67(2):133-9. doi: 10.1111/j.1365-3083.2007.02048.x.
Tuberculosis (TB) caused by Mycobacterium tuberculosis continues to be one of the major public health problems in the world. The eventual control of this disease will require the development of a safe and effective vaccine. Bacille Calmette-Guerin (BCG), the only vaccine against TB, is not perfect for its limited ability to protect against the adult form of TB. Some improvements of TB vaccines relied to strengthening the immunogenicity and/or persistence of genetically modified recombinant BCG (rBCG) strain. Antigen 85B (Ag85B) and Mtb8.4 are importantly immunodominant antigens of M. tuberculosis, and both are very promising vaccine candidate molecules. MPT64(190-198), is presented to CD8(+) T cells during mycobacterial infections. In this study, we combined these above genes into one recombinant gene of ag85B-mpt64(190-198)-mtb8.4. Then we constructed the new rBCG containing this united gene. This rBCG can induce an increased Th1-type immune response in mice, characterized by an elevated level of interferon-gamma in antigen-stimulated splenocyte culture and a strong IgG2a antibody response. Also, it can elicit longer immune responses than BCG. The results show that this rBCG is a promising candidate for further study.
由结核分枝杆菌引起的结核病仍然是世界上主要的公共卫生问题之一。最终控制这种疾病需要研发一种安全有效的疫苗。卡介苗（BCG）是唯一的抗结核疫苗，但因其预防成人型结核病的能力有限而并不完美。一些结核病疫苗的改进依赖于增强基因改造重组卡介苗（rBCG）菌株的免疫原性和/或持久性。抗原85B（Ag85B）和Mtb8.4是结核分枝杆菌重要的免疫显性抗原，二者都是非常有前景的疫苗候选分子。MPT64(190 - 198)在分枝杆菌感染期间会呈递给CD8(+) T细胞。在本研究中，我们将上述基因组合成一个ag85B - mpt64(190 - 198) - mtb8.4的重组基因。然后构建了含有该联合基因的新型rBCG。这种rBCG能在小鼠体内诱导增强的Th1型免疫反应，其特征为抗原刺激的脾细胞培养物中γ干扰素水平升高以及强烈的IgG2a抗体反应。此外，它能引发比卡介苗更长时间的免疫反应。结果表明，这种rBCG是进一步研究的一个有前景的候选疫苗。
