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沙眼衣原体血清型 F 型、天然主要外膜蛋白疫苗在非人灵长类动物模型中的免疫原性。

Immunogenicity of a vaccine formulated with the Chlamydia trachomatis serovar F, native major outer membrane protein in a nonhuman primate model.

机构信息

Department of Pathology and Laboratory Medicine, Medical Sciences I, Room D440, University of California, Irvine, Irvine, CA 92697-4800, USA.

出版信息

Vaccine. 2011 Apr 18;29(18):3456-64. doi: 10.1016/j.vaccine.2011.02.057. Epub 2011 Mar 4.

Abstract

To determine the ability of a vaccine formulated with the genital Chlamydia trachomatis, serovar F, native major outer membrane protein (Ct-F-nMOMP), to induce systemic and mucosal immune responses, rhesus macaques (Macaca mulatta) were immunized three times by the intramuscular (i.m.) and subcutaneous (s.c.) routes using CpG-2395 and Montanide ISA 720 VG, as adjuvants. As controls, another group of M. mulatta was immunized with ovalbumin instead of Ct-F-nMOMP using the same formulation and routes. High levels of Chlamydia-specific IgG and IgA antibodies were detected in plasma, vaginal washes, tears, saliva, and stools from the Ct-F-nMOMP immunized animals. Also, high neutralizing antibody titers were detected in the plasma from these animals. Monkeys immunized with ovalbumin had no detectable Chlamydia-specific antibodies. Furthermore, as measured by a lymphoproliferative assay, significant Chlamydia-specific cell-mediated immune responses were detected in the peripheral blood mononuclear cells (PBMC) from the rhesus macaques vaccinated with Ct-F-nMOMP when compared with the animals immunized with ovalbumin. In addition, the levels of two Th1 cytokines, IFN-γ and TNF-α, were significantly higher in the animals immunized with Ct-F-nMOMP when compared with those from the monkeys immunized with ovalbumin. To our knowledge, this is the first time that mucosal and systemic immune responses have been investigated in a nonhuman primate model using a subunit vaccine from a human genital C. trachomatis serovar.

摘要

为了确定用生殖器沙眼衣原体血清型 F 天然主要外膜蛋白(Ct-F-nMOMP)制成的疫苗诱导全身和粘膜免疫应答的能力,恒河猴(Macaca mulatta)通过肌肉内(i.m.)和皮下(s.c.)途径用 CpG-2395 和 Montanide ISA 720 VG 作为佐剂进行了三次免疫接种。作为对照,另一组恒河猴使用相同的制剂和途径用卵清蛋白代替 Ct-F-nMOMP 进行免疫接种。从 Ct-F-nMOMP 免疫的动物的血浆、阴道冲洗液、眼泪、唾液和粪便中检测到高水平的沙眼衣原体特异性 IgG 和 IgA 抗体。此外,还从这些动物的血浆中检测到高中和抗体滴度。用卵清蛋白免疫的猴子没有检测到特异性的沙眼衣原体抗体。此外,通过淋巴细胞增殖试验测量,与用卵清蛋白免疫的动物相比,用 Ct-F-nMOMP 免疫的恒河猴外周血单核细胞(PBMC)中检测到显著的沙眼衣原体特异性细胞介导的免疫应答。此外,与用卵清蛋白免疫的猴子相比,用 Ct-F-nMOMP 免疫的动物中两种 Th1 细胞因子 IFN-γ和 TNF-α的水平显著升高。据我们所知,这是首次在非人灵长类动物模型中使用来自人生殖道沙眼衣原体血清型的亚单位疫苗来研究粘膜和全身免疫应答。

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