State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China.
Scand J Immunol. 2012 Sep;76(3):271-7. doi: 10.1111/j.1365-3083.2012.02726.x.
Tuberculosis (TB) remains an enormous global health problem, and a new vaccine against TB more potent than the current inadequate vaccine, the Bacille Calmette-Guérin (BCG), is urgently needed. BCG has proven to be an effective recombinant delivery vehicle for foreign antigens because of its ability to induce long-lived specific humoral and cellular immunity. Experimental evidences have revealed that Ag85B, ESAT-6 and Rv2608 are important immunodominant antigens of Mycobacterium tuberculosis and are all promising vaccine candidate molecules. In this study, we have constructed a novel recombinant BCG (rBCG) expressing fusion protein Ag85B-ESAT6-Rv2608 and evaluated the immunogenicity of rBCG in C57BL/6 mice. Results show there is strong TB-specific CD4⁺ and CD8⁺ T lymphocytes proliferative response in mice immunized with rBCG vaccine, especially the cytotoxic CD8⁺ T cells playing an important role in protection against TB. And rBCG immunization has induced a significantly strong Th1 immune response, characterized by the increased ratio of IgG2b/IgG1. Results also show that rBCG immunization could increase the secretion of Th1 cytokines such as TNF-α and IL-2 and could decrease the secretion of Th2 cytokine IL-10. Moreover, it was shown that rBCG immunization induced a strong humoral response in mice, characterized by the elevated IgG titre. Therefore, we conclude that this rBCG immunization could increase both cellular immune response and antigen-specific humoral response significantly as compared to BCG immunization in mice. The above results illustrated that rBCG::Ag85B-ESAT6-Rv2608 is a potential candidate against M. tuberculosis for further study.
结核病（TB）仍然是一个巨大的全球健康问题，迫切需要一种比目前效果不佳的卡介苗（BCG）更强效的针对结核病的新型疫苗。由于能够诱导长期存在的特异性体液和细胞免疫，BCG 已被证明是一种有效的重组外来抗原传递载体。实验证据表明，Ag85B、ESAT-6 和 Rv2608 是结核分枝杆菌的重要免疫优势抗原，都是很有前途的候选疫苗分子。在本研究中，我们构建了一种表达融合蛋白 Ag85B-ESAT6-Rv2608 的新型重组卡介苗（rBCG），并评估了 rBCG 在 C57BL/6 小鼠中的免疫原性。结果表明，rBCG 疫苗免疫的小鼠中存在强烈的结核特异性 CD4⁺和 CD8⁺T 淋巴细胞增殖反应，尤其是细胞毒性 CD8⁺T 细胞在抗结核保护中发挥重要作用。并且 rBCG 免疫诱导了强烈的 Th1 免疫反应，表现为 IgG2b/IgG1 的比值增加。结果还表明，rBCG 免疫可增加 Th1 细胞因子如 TNF-α和 IL-2 的分泌，并降低 Th2 细胞因子 IL-10 的分泌。此外，研究表明 rBCG 免疫可诱导小鼠产生强烈的体液反应，表现为 IgG 滴度升高。因此，与 BCG 免疫相比，rBCG 免疫可显著增强细胞免疫反应和抗原特异性体液反应。上述结果表明，rBCG::Ag85B-ESAT6-Rv2608 是一种有潜力的抗结核分枝杆菌候选疫苗，值得进一步研究。
