Cheng Chunmei, Bettahi Ilham, Cruz-Fisher Maria I, Pal Sukumar, Jain Pooja, Jia Zhenyu, Holmgren Jan, Harandi Ali M, de la Maza Luis M
Department of Pathology and Laboratory Medicine, Medical Sciences, I, Room D440, University of California, Irvine, CA 92697-4800, USA.
Vaccine. 2009 Oct 19;27(44):6239-46. doi: 10.1016/j.vaccine.2009.07.108. Epub 2009 Aug 15.
The present study was undertaken to test the efficacy of immunization with the native major outer membrane protein (nMOMP) of Chlamydia trachomatis mouse pneumonitis (MoPn) serovar in combination with a novel immunostimulatory adjuvant consisting of CpG oligodeoxynucleotide (ODN) linked to the nontoxic B subunit of cholera toxin (CTB-CpG) to elicit a protective immune response to C. trachomatis. High levels of Chlamydia-specific IgG antibodies were detected in the sera from BALB/c mice immunized intramuscularly and subcutaneously (i.m.+s.c.) with the nMOMP/CTB-CpG vaccine or with nMOMP adjuvanted with a mixture of CT and CpG ODN (CT+CpG). Further, these immunization schemes gave rise to significant T-cell-mediated Chlamydia-specific immune responses. No Chlamydia-specific humoral or cell-mediated immune responses were detected in the control mice vaccinated with ovalbumin together with either CTB-CpG or CT+CpG. Following an intranasal challenge with C. trachomatis the groups of mice immunized with nMOMP plus CTB-CpG, CT+CpG or live C. trachomatis were found to be protected based on their change in body weight and lung weight as well as number of inclusion forming unit recovered from the lungs, as compared with control groups immunized with ovalbumin plus either adjuvants. Interestingly, IFN-gamma-producing CD4(+), but not CD8(+), T-cells showed a significant correlation with the outcomes of the challenge. In conclusion, nMOMP in combination with the novel adjuvant CTB-CpG elicited a significant antigen-specific antibody and cell-mediated immune responses as well as protection against a pulmonary challenge with C. trachomatis.
本研究旨在测试沙眼衣原体鼠肺炎(MoPn)血清型的天然主要外膜蛋白(nMOMP)与一种新型免疫刺激佐剂联合免疫的效果,该佐剂由与霍乱毒素无毒B亚基(CTB-CpG)连接的CpG寡脱氧核苷酸(ODN)组成,以引发对沙眼衣原体的保护性免疫反应。在用nMOMP/CTB-CpG疫苗或用CT和CpG ODN混合物(CT+CpG)佐剂的nMOMP进行肌肉内和皮下(i.m.+s.c.)免疫的BALB/c小鼠血清中检测到高水平的沙眼衣原体特异性IgG抗体。此外,这些免疫方案引发了显著的T细胞介导的沙眼衣原体特异性免疫反应。在用卵清蛋白与CTB-CpG或CT+CpG一起接种的对照小鼠中未检测到沙眼衣原体特异性体液或细胞介导的免疫反应。在用沙眼衣原体进行鼻内攻击后,发现用nMOMP加CTB-CpG、CT+CpG或活沙眼衣原体免疫的小鼠组,根据其体重和肺重量的变化以及从肺中回收的包涵体形成单位数量,与用卵清蛋白加任何一种佐剂免疫的对照组相比受到了保护。有趣的是,产生IFN-γ的CD4(+)而非CD8(+) T细胞与攻击结果显示出显著相关性。总之,nMOMP与新型佐剂CTB-CpG联合引发了显著的抗原特异性抗体和细胞介导的免疫反应以及对沙眼衣原体肺部攻击的保护作用。