Institute of Neurobiology and Molecular Medicine, National Research Council, Via del Fosso del Cavaliere 100, 00133 Rome, Italy.
Microb Pathog. 2010 May;48(5):150-9. doi: 10.1016/j.micpath.2010.02.003. Epub 2010 Feb 26.
One possibility to improve the efficacy of BCG vaccine against TB is to create a recombinant BCG (r-BCG), increasing the expression of mycobacterial antigens, to ameliorate the response to BCG. Here we describe a new r-BCG expressing the gene Rv1767, induced by Mycobacterium tuberculosis during its survival in human macrophages. The r-BCG elicited a specific T cells response in Balb/c mice higher than wt BCG. The r-BCG amount used to immunise mice determined diverse Th1/Th2 equilibriums, which was not the same in spleen and Lymph Nodes. Differences in cytokines production were found for IL-10, IL-4, TNF-alpha, and Arginase-1, which, in some conditions, resulted higher in r-BCG as compared to wt BCG-immunised mice. The immunisation with r-BCG-Rv1767 induced a lesser protective activity than wt BCG in a mouse model of TB. This reduction might likely be explained by the specific T cells phenotype and setting existing before MTB challenge, induced by either the single or the triple dose of r-BCG. The use of this model may help to highlight the capacity of different M. tuberculosis antigens to induce a protective immune response, actually not necessarily embodied by an increased frequency of Antigen-specific effector memory T cells.
提高卡介苗（BCG）疫苗预防结核病疗效的一种可能性是创建重组卡介苗（r-BCG），增加分枝杆菌抗原的表达，以改善对 BCG 的反应。在这里，我们描述了一种新的 r-BCG，它表达了结核分枝杆菌在人类巨噬细胞中生存时诱导的基因 Rv1767。r-BCG 在 Balb/c 小鼠中引发的特异性 T 细胞反应高于野生型 BCG。r-BCG 用于免疫小鼠的量决定了不同的 Th1/Th2 平衡，在脾脏和淋巴结中并不相同。对于白细胞介素 10（IL-10）、白细胞介素 4（IL-4）、肿瘤坏死因子-α（TNF-α）和精氨酸酶-1，发现了不同的细胞因子产生差异，在某些条件下，r-BCG 比野生型 BCG 免疫的小鼠产生的更高。在结核病小鼠模型中，r-BCG-Rv1767 的免疫接种引起的保护活性低于野生型 BCG。这种减少可能是由于在 MTB 挑战之前，单一或三剂量 r-BCG 诱导的特定 T 细胞表型和现有环境引起的。使用这种模型可以帮助突出不同结核分枝杆菌抗原诱导保护性免疫反应的能力，实际上不一定表现为抗原特异性效应记忆 T 细胞的频率增加。
