Evaluation of a multisubunit recombinant polymorphic membrane protein and major outer membrane protein T cell vaccine against Chlamydia muridarum genital infection in three strains of mice.
Evaluation of a multisubunit recombinant polymorphic membrane protein and major outer membrane protein T cell vaccine against Chlamydia muridarum genital infection in three strains of mice.
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多亚基重组多态性膜蛋白和主要外膜蛋白 T 细胞疫苗对三种小鼠品系小鼠衣原体生殖器感染的评价。
DOI：
10.1016/j.vaccine.2014.06.002
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发表时间：
2014
期刊：
影响因子：
5.5
通讯作者：
Brunham,RobertC
中科院分区：
文献类型：
--
作者：
Yu,Hong;Karunakaran,KarunaP;Jiang,Xiaozhou;Brunham,RobertC
控制沙眼衣原体感染需要一种有效的疫苗。在衣原体感染小鼠模型中，多功能粘膜CD4T细胞是保护性免疫的基础，抗体起次要作用。我们先前使用基于树突状细胞的免疫蛋白质组学方法确定了四种衣原体外膜蛋白(PMPE、PMPF、PmpG和PmpH)作为CD4T细胞疫苗候选。在C57BL/6小鼠生殖道模型中，通过加速清除衣原体感染，我们还证明了这四种多态膜蛋白(PMPs)分别具有保护作用。MOMP是主要的外膜蛋白，也是该系统中研究得很好的保护性疫苗抗原。在本研究中，我们测试了由四种PMP(PmpEFGH)组成的多亚单位重组蛋白疫苗(PmpEFGH)在C57BL/6、Balb/c和C3H小鼠中的免疫原性和保护性。我们发现，用PmpEFGH+MMOMP免疫的C57BL/6小鼠比用单个蛋白抗原免疫的小鼠产生了更强劲的细胞免疫反应。在三个品系的小鼠中，PMPs比MOMP能引起更多不同的细胞免疫反应。联合疫苗加速了三个品系的小鼠的清除，尽管速度不同。我们的结论是，重组外膜蛋白组合构成了一种有希望的第一代衣原体疫苗构建物，应该能在远交群体中提供广泛的免疫原性。
An efficacious vaccine is needed to controlChlamydia trachomatisinfection. In the murine model ofChlamydia muridarumgenital infection, multifunctional mucosal CD4 T cells are the foundation for protective immunity, with antibody playing a secondary role. We previously identified fourChlamydiaouter membrane proteins (PmpE, PmpF, PmpG and PmpH) as CD4 T cell vaccine candidates using a dendritic cell-based immunoproteomic approach. We also demonstrated that these four polymorphic membrane proteins (Pmps) individually conferred protection as measured by accelerated clearance ofChlamydiainfection in the C57BL/6 murine genital tract model. The major outer membrane protein, MOMP is also a well-studied protective vaccine antigen in this system. In the current study, we tested immunogenicity and protection of a multisubunit recombinant protein vaccine consisting of the four Pmps (PmpEFGH) with or without the major outer membrane protein (MOMP) formulated with a Th1 polarizing adjuvant in C57BL/6, Balb/c and C3H mice. We found that C57BL/6 mice vaccinated with PmpEFGH + MOMP elicited more robust cellular immune responses than mice immunized with individual protein antigens. Pmps elicited more variable cellular immune responses than MOMP among the three strains of mice. The combination vaccine accelerated clearance in the three strains of mice although at different rates. We conclude that the recombinant outer membrane protein combination constitutes a promising first generationChlamydiavaccine construct that should provide broad immunogenicity in an outbred population.