沙眼衣原体分泌性蛋白Pgp3滴鼻免疫增强小鼠对衣原体生殖道感染的保护作用

Intranasal immunization with secretion protein Pgp3 enhances protective immunity against mice genital Chlamydia muridarum infection

摘要:

【目的】探讨不同免疫途径沙眼衣原体(Chlamydia trachomatis, Ct)分泌性蛋白Pgp3的免疫保护效果, 分析其可能的保护机制, 以确定Pgp3蛋白疫苗在Ct疫苗研制中的应用价值。【方法】分泌性蛋白Pgp3经滴鼻或肌注途径免疫雌性Balb/c小鼠, 免疫60 d后, 阴道接种鼠沙眼衣原体(Chlamydia muridarum, Cm) 建立生殖道感染动物模型, 在该模型中评价Pgp3蛋白疫苗抗Cm感染的保护效果, 并探讨其机制。【结果】滴鼻或肌注免疫后, 小鼠血清及生殖道中检测到了特异性抗体; 小鼠脾淋巴细胞产生IFN-γ、IL-17及IL-5水平均明显高于对照组, 且滴鼻免疫组IFN-γ水平升高较肌注组更显著(P<0.05); Pgp3蛋白滴鼻免疫组小鼠经Cm生殖道感染后, 阴道带菌时间明显缩短, 输卵管病理改变轻而肌注免疫组其保护作用不明显。【结论】Pgp3蛋白经滴鼻免疫可有效诱导小鼠产生明显的抗Cm保护效应。其可能的免疫保护机制与诱导Th1型为主的细胞免疫应答及高效价的特异性抗体有关, 提示Pgp3蛋白疫苗具有潜在的疫苗研究与开发价值。

Abstract:

[Objective] To validate the immune protective efficacy of Chlamydia secretion protein Pgp3 and to analyze the potential immune mechanisms related to this protection. [Methods] The prokaryotic recombinant protein Pgp3 was purified and evaluated for its pro-tective efficacy in a genital tract infected mouse model. Groups of BALB/c mice were immu-nized intranasally or intramuscularly with adjuvants plus Pgp3 protein or PBS and GST con-trol. Humoral and cellular immune responses were evaluated. After Chlamydia muridarum in-travaginal challenge, the chlamydia shedding from the lower genital tract and the chlamy-dia-induced upper genital tract gross pathology and histopathological characterization were also detected. [Results] Adjuvant plus Pgp3 immunization can induce high level of Pgp3 spe-cific antibody as well as IFN-γ, IL-17 and IL-5 cytokine production. More importantly, intra-nasal immunization compare with intramuscular route induced more Th1-dominant immunity that significantly reduced the shedding of live organisms from the lower genital tract and at-tenuated inflammatory pathologies in the oviduct tissues. [Conculsion] These observations have demonstrated that secretion protein Pgp3 intranasal immunization can induce protective immunity against chlamydial infection and pathology in mice.