Department of Pathology and Laboratory Medicine, Medical Sciences 1, Room D440, University of California, Irvine, Irvine, CA 92697-4800, USA.
Vaccine. 2011 Mar 16;29(13):2437-43. doi: 10.1016/j.vaccine.2011.01.031. Epub 2011 Jan 26.
IC31(®), a novel adjuvant, has been shown to be effective by increasing the levels of IFN-γ in animal models when delivered with several antigens. Here, we tested the ability of IC31(®), to enhance the protective ability of the Chlamydia trachomatis native major outer membrane protein (nMOMP). BALB/c mice were immunized by the intramuscular (i.m.) and subcutaneous (s.c.) routes with nMOMP+IC31(®). Another group of animals was immunized with nMOMP+Alum and as a negative control mice were immunized with ovalbumin (Ova)+IC31(®). Animals immunized with nMOMP+IC31(®) developed high Chlamydia-specific IgG titers. The serum levels of IgG1 were higher than those of the IgG2a. T cells, from the spleens of mice immunized with IC31(®)-adjuvanted nMOMP demonstrated a strong lymphoproliferative reaction to Chlamydia elementary bodies (EB) compared with the groups immunized with nMOMP+Alum or Ova+IC31(®). A similar comparison between these groups of mice revealed that the levels of IFN-γ in the supernatants from stimulated T-cells were significantly higher in animals immunized with nMOMP+IC31(®). Following an intranasal challenge with C. trachomatis, the mice immunized with IC31(®)-adjuvanted nMOMP showed significant protection. The change in body weight, an indication of the severity of the infection, was significantly less reduced in mice immunized with nMOMP+IC31(®). Furthermore, the weight of the lungs, as well as the pulmonary Chlamydia burden, was significantly lower in the animals immunized with nMOMP+IC31(®) when compared with the groups immunized with nMOMP+Alum or with Ova+IC31(®). In conclusion, these results provide the rationale for further preclinical testing of IC31(®) using other chlamydial antigens, and support the potential evaluation of this adjuvant in human vaccines against Chlamydia.
IC31(®) 是一种新型佐剂,当与几种抗原一起使用时,在动物模型中显示出通过增加 IFN-γ 水平而有效。在这里,我们测试了 IC31(®) 增强沙眼衣原体天然主要外膜蛋白 (nMOMP) 的保护能力的能力。BALB/c 小鼠通过肌肉内 (i.m.) 和皮下 (s.c.) 途径用 nMOMP+IC31(®) 免疫。另一组动物用 nMOMP+Alum 免疫,作为阴性对照,用卵清蛋白 (Ova)+IC31(®) 免疫。用 nMOMP+IC31(®) 免疫的动物产生了高的衣原体特异性 IgG 滴度。血清 IgG1 水平高于 IgG2a。与用 nMOMP+Alum 或 Ova+IC31(®) 免疫的组相比,来自用 IC31(®) 佐剂 nMOMP 免疫的小鼠脾脏的 T 细胞对衣原体原体 (EB) 表现出强烈的淋巴增殖反应。对这些组的小鼠进行类似的比较表明,在用 nMOMP+IC31(®) 免疫的动物中,从刺激的 T 细胞上清液中 IFN-γ 的水平明显更高。在用 C. trachomatis 进行鼻内攻击后,用 IC31(®) 佐剂 nMOMP 免疫的小鼠表现出显著的保护作用。用 nMOMP+IC31(®) 免疫的小鼠的体重变化(感染严重程度的指示)明显减少。此外,与用 nMOMP+Alum 免疫的组或用 Ova+IC31(®) 免疫的组相比,用 nMOMP+IC31(®) 免疫的动物的肺部重量和肺部衣原体负担明显降低。总之,这些结果为使用其他衣原体抗原进一步进行 IC31(®) 的临床前测试提供了依据,并支持在针对衣原体的人类疫苗中评估这种佐剂的潜力。