结核分枝杆菌感染小鼠模型中 Ag85 复合物蛋白佐剂亚单位疫苗的辅助免疫治疗。
Adjunct immunotherapy with Ag85 complex proteins based subunit vaccine in a murine model of Mycobacterium tuberculosis infection.
机构信息
University of Notre Dame, IN, USA.
出版信息
Immunotherapy. 2009 Jan;1(1):31-7. doi: 10.2217/1750743X.1.1.31.
This study was designed to evaluate the immunotherapeutic potential of Mycobacterium tuberculosis Ag85AB emulsified with unmethylated CpG motif-containing oligonucleotide (CpG-ODN) and dimethyldioctadecylammonium bromide (DDA) adjuvants (Ag85AB-CpG-DDA) in conjunction with antituberculous drugs. Ag85 complex proteins of M. tuberculosis purified from total culture filtrate and purified proteins were emulsified with CpG-ODN and DDA adjuvants. Mice were infected with M. tuberculosis H37 Rv and left for 30 days to establish infection. These mice were named 'tuberculous mice'. Tuberculous mice were treated with Ag85AB-CpG-DDA alone or in conjunction with antituberculous drugs. Treatment of tuberculous mice with Ag85AB-CpG-DDA in conjunction with antituberculous drugs reduced significant bacilli burden in lung and spleen. Moreover, treatment of tuberculous mice with Ag85AB-CpG-DDA induced higher production of type-I cytokines, generated more CD44-positive T cells and suppresses secretion of IL-4 as compared with untreated animals. In conclusion, this study shows that Ag85AB-CpG-DDA formulation may act as a potential future therapeutic regimen in conjunction with antituberculous drugs.
本研究旨在评估结核分枝杆菌 Ag85AB 与未甲基化 CpG 基序含有寡核苷酸（CpG-ODN）和二甲基二十八烷基溴化铵（DDA）佐剂（Ag85AB-CpG-DDA）联合抗结核药物的免疫治疗潜力。从总培养滤液中提取结核分枝杆菌的 Ag85 复合物蛋白，并与 CpG-ODN 和 DDA 佐剂乳化。用结核分枝杆菌 H37Rv 感染小鼠，并放置 30 天以建立感染。这些小鼠被命名为“结核小鼠”。用 Ag85AB-CpG-DDA 单独或联合抗结核药物治疗结核小鼠。与未处理的动物相比，用 Ag85AB-CpG-DDA 联合抗结核药物治疗结核小鼠可显著减少肺和脾脏中的细菌负担。此外，与未处理的动物相比，用 Ag85AB-CpG-DDA 治疗结核小鼠可诱导更高水平的 I 型细胞因子产生，产生更多的 CD44 阳性 T 细胞，并抑制 IL-4 的分泌。总之，这项研究表明，Ag85AB-CpG-DDA 制剂可能与抗结核药物联合成为一种有前途的未来治疗方案。
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