We have shown previously that intranasal vaccination with recombinant chlamydial protease-like activity factor (rCPAF: antigen) and interleukin-12 (IL-12) as an adjuvant induces robust protection against pathological consequences of female genital tract infection with Chlamydia muridarum, a closely related species and a rodent model for the human pathogen Chlamydia trachomatis. Another related species Chlamydia pneumoniae, a human respiratory pathogen, has been associated with exacerbation of atherosclerotic pathology. CPAF is highly conserved among Chlamydia spp. leading us to hypothesize that immunization with rCPAF with IL-12 will protect against high-fat diet (HFD) and C. pneumoniae-induced acceleration of atherosclerosis. rCPAF ± IL-12 immunization induced robust splenic antigen (Ag)-specific IFN-γ and TNF-α production and significantly elevated serum total anti-CPAF Ab, IgG2c, and IgG1 antibody levels compared to mock or IL-12 alone groups. The addition of IL-12 to rCPAF significantly elevated splenic Ag-specific IFN-γ production and IgG2c/IgG1 anti-CPAF antibody ratio. Following intranasal C. pneumoniae challenge and HFD feeding, rCPAF ± IL-12-immunized mice displayed significantly enhanced splenic IFN-γ, not TNF-α, response on days 6 and 9 after challenge, and significantly reduced lung chlamydial burden on day 9 post-challenge compared to mock- or IL-12-immunized mice. Importantly, rCPAF ± IL-12-immunized mice displayed significantly reduced atherosclerotic pathology in the aortas after C. pneumoniae challenge. Serum cholesterol levels were comparable between the groups suggesting that the observed differences in pathology were due to protective immunity against the infection. Together, these results confirm and extend our previous observations that CPAF is a promising candidate antigen for a multisubunit vaccine regimen to protect against Chlamydia-induced pathologies, including atherosclerosis.

中文翻译：

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用重组衣原体蛋白酶样活性因子进行鼻内免疫可减轻小鼠肺炎衣原体感染后的动脉粥样硬化病理。

以前我们已经表明，鼻腔内接种重组衣原体蛋白酶样活性因子（rCPAF：抗原）和白介素12（IL-12）作为佐剂可有效抵抗女性生殖道感染衣原体（密切相关）的病理后果人类病原体沙眼衣原体的物种和啮齿动物模型。另一相关物种肺炎衣原体，一种人类呼吸道病原体，与动脉粥样硬化病理的恶化有关。CPAF在衣原体中是高度保守的。导致我们假设，用IL-12的rCPAF进行免疫可以预防高脂饮食（HFD）和肺炎衣原体诱导的动脉粥样硬化的加速。与单独的模拟组或单独的IL-12组相比，rCPAF±IL-12免疫诱导了强大的脾脏抗原（Ag）特异性IFN-γ和TNF-α的产生，并显着提高了血清总抗CPAF Ab，IgG2c和IgG1抗体的水平。向rCPAF中添加IL-12可显着提高脾脏Ag特异性IFN-γ的产生和IgG2c / IgG1抗CPAF抗体的比例。鼻内肺炎衣原体攻击和HFD喂养后，经rCPAF±IL-12免疫的小鼠在攻击后第6天和第9天表现出明显增强的脾脏IFN-γ（而非TNF-α）反应，并在术后第9天显着降低了肺衣原体负担与模拟免疫或IL-12免疫的小鼠相比具有更大的挑战性。重要的是，在肺炎衣原体感染后，rCPAF±IL-12免疫的小鼠在主动脉中显示出明显降低的动脉粥样硬化病理。两组之间的血清胆固醇水平相当，这表明观察到的病理学差异是由于对感染的保护性免疫所致。总之，这些结果证实并扩展了我们先前的观察结果，即CPAF是多亚单位疫苗方案中有希望的候选抗原，可以预防衣原体诱导的疾病，包括动脉粥样硬化。