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Comparison of Chlamydia outer membrane complex to recombinant outer membrane proteins as vaccine.
Vaccine ( IF 5.5 ) Pub Date : 2020-03-06 , DOI: 10.1016/j.vaccine.2020.02.059
Hong Yu 1 , Karuna P Karunakaran 1 , Xiaozhou Jiang 1 , Queenie Chan 2 , Caren Rose 3 , Leonard J Foster 2 , Raymond M Johnson 4 , Robert C Brunham 1
Affiliation  

The Chlamydial outer membrane complex (COMC) from the elementary body (EB) is a protein rich insoluble outer membrane shell from which cytosolic proteins have been extracted with detergent. In this study we conducted mass spectrometry experiments to detect proteins in the COMC prepared from C. muridarum EB. Proteomic analysis showed that the COMC contained 75 proteins that included 10 outer membrane proteins (OMPs) such as the major outer membrane protein (MOMP) and polymorphic membrane proteins (Pmps) that were previously identified as CD4 T cell vaccine candidates. We tested the vaccine efficacy of COMC in comparison to individual or combination of recombinant OMPs formulated with Th1 polarizing adjuvant DDA/MPL in two murine genital tract models (C. muridarum and C. trachomatis) by measuring organismal shedding, tubal pathology and immune responses including neutralizing antibodies. In the C. muridarum model, the COMC vaccine generated broadly reactive immune responses against multiple outer membrane proteins, high levels of EB binding and neutralizing antibody and exhibited superior protection against genital infection and pathology when compared to the recombinant PmpG vaccine. Denaturing the COMC by boiling significantly reduced protection. In the C. trachomatis model, the COMC vaccine also conferred greater protection compared to individual or multiple recombinant outer membrane proteins. Immunization with multiple COMCs from C. trachomatis serovars D, F and J generated neutralizing antibodies against multiple C. trachomatis serovars. We conclude that broader immunogenicity and generation of neutralizing antibody may explain the superior efficacy of COMC vaccine. The study suggests that conformationally intact proteins will be necessary for a successful recombinant OMP vaccine.



中文翻译:

衣原体外膜复合物与重组外膜蛋白作为疫苗的比较。

来自基本体(EB)的衣原体外膜复合物(COMC)是富含蛋白质的不溶性外膜壳,已经用去污剂从中提取了胞质蛋白。在这项研究中,我们进行了质谱实验,以检测由muridarum EB制备的COMC中的蛋白质。蛋白质组学分析表明,COMC包含75种蛋白质,其中包括10种外膜蛋白(OMP),例如以前被鉴定为CD4 T细胞疫苗候选物的主要外膜蛋白(MOMP)和多态膜蛋白(Pmps)。我们在两个鼠生殖道模型(C. muridarum)中,比较了用Th1极化佐剂DDA / MPL配制的重组OMP的个体或组合与COMC的疫苗功效沙眼衣原体C. trachomatis)),方法是测量生物体脱落,输卵管病理和免疫反应,包括中和抗体。在鼠疫衣原体模型中,与重组PmpG疫苗相比,COMC疫苗对多种外膜蛋白产生广泛的反应性免疫反应,具有高水平的EB结合和中和抗体,并且对生殖器感染和病理表现出优异的保护作用。通过煮沸使COMC变性会大大降低保护作用。在沙眼衣原体模型中,与单个或多个重组外膜蛋白相比,COMC疫苗还具有更大的保护作用。用沙眼衣原体的多个COMC进行免疫血清D,F和J产生针对多种沙眼衣原体血清的中和抗体。我们得出结论,更广泛的免疫原性和中和抗体的产生可能解释了COMC疫苗的优越功效。研究表明,构象完整的蛋白对于成功的重组OMP疫苗是必要的。

更新日期:2020-03-09
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