Department of Bioscience and Biotechnology, College of Bioscience, Sejong University, 98 Kunja-dong, Kwangjin-gu, Seoul 143-747, Republic of Korea.
Int Immunopharmacol. 2011 Sep;11(9):1195-204. doi: 10.1016/j.intimp.2011.03.020. Epub 2011 Apr 12.
Anthrax is an infectious disease caused by Bacillus anthracis. The currently licensed human anthrax vaccines contain protective antigen (PA) as a major protective component and alum as an adjuvant. In this study, we investigated whether CIA05, a TLR4 agonist, is able to promote the immune response to an anthrax vaccine adjuvanted with alum. BALB/c mice were immunized intraperitoneally three times at 2-week intervals with a recombinant B. anthracis PA alone or in combination with CIA05 in the absence or presence of alum, and immune responses were determined 2 or 3 weeks after the third immunization. The results showed that the combination of CIA05 and alum significantly increased both serum anti-PA IgG antibody and toxin-neutralizing antibody titers, and the adjuvant effects were greater when lower antigen doses were used for immunization. Both CIA05 and alum stimulated PA-specific splenocyte secretion of interleukin (IL)-4, IL-5, and IL-6. A combination of the two yielded synergistic effects on IL-4 secretion, but CIA05 tended to repress IL-5 and IL-6 secretions induced by alum. Co-administration of CIA05 and alum also increased GL7 expression in B220(+)CD24(+) splenic cells, indicating the ability to activate B cells. These data suggest that CIA05, combined with alum, could be used to achieve higher immune responses to PA, leading to the development of an effective anthrax vaccine.
炭疽是由炭疽杆菌引起的传染病。目前批准的人类炭疽疫苗含有保护性抗原（PA）作为主要保护成分和明矾作为佐剂。在这项研究中，我们研究了 TLR4 激动剂 CIA05 是否能够促进对明矾佐剂炭疽疫苗的免疫反应。BALB/c 小鼠每隔 2 周通过腹膜内免疫三次重组炭疽 PA 单独或与 CIA05 联合使用，在第三次免疫后 2 或 3 周测定免疫反应。结果表明，CIA05 和明矾的联合使用显著增加了血清抗 PA IgG 抗体和毒素中和抗体滴度，并且当使用较低的抗原剂量进行免疫时，佐剂效果更大。CIA05 和明矾均刺激 PA 特异性脾细胞分泌白细胞介素（IL）-4、IL-5 和 IL-6。两者的组合对 IL-4 分泌具有协同作用，但 CIA05 倾向于抑制明矾诱导的 IL-5 和 IL-6 分泌。CIA05 和明矾的共同给药还增加了 B220(+)CD24(+)脾细胞中 GL7 的表达，表明能够激活 B 细胞。这些数据表明，CIA05 与明矾联合使用可以增强对 PA 的免疫反应，从而开发出有效的炭疽疫苗。
