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卡他莫拉菌脂膜相关外膜蛋白(OMPs)的免疫原性。

The immunogenicity of the liposome-associated outer membrane proteins (OMPs) of Moraxella catarrhalis.

机构信息

Laboratory of Immunology, Institute of Genetics and Microbiology, University of Wrocław, Przybyszewskiego 63/77, 51-148 Wrocław, Poland.

出版信息

Cell Mol Biol Lett. 2010;15(1):70-89. doi: 10.2478/s11658-009-0035-z. Epub 2009 Oct 22.

Abstract

The outer membrane proteins (OMPs) are the most immunogenic and attractive of the Moraxella catarrhalis vaccine antigens that may induce the protective immune response. The aim of this study was to determine the effectiveness of two types of OMP-associated phosphatidylcholine (PC) liposomal formulations (OMPs-PC, PC-OMPs) and of Zwittergent-based proteomicelles (OMPs-Z) in potentiating an anti-OMP systemic immune response in mice. The immunogenicities of the above preparations were evaluated by assessing serum anti-OMP IgG and IgA reactivity in the post-immunized mouse antisera using ELISA and Western blotting. Additionally, the cross-reactivity of the most effective anti-OMP response was determined using heterologous sera from both humans and mice. Both the proteoliposomes and the proteomicelles showed high immunogenic properties and did not elicit any distinct quantitative differences in the antibody titer or qualitative differences in the pattern of the mouse antisera. The post-immunized mouse antisera predominantly recognized a approximately 60-kDa OMP of M. catarrhalis. That protein was also found to be a highly cross-reactive antigen interacting with a panel of pooled mouse antisera produced by immunization either with whole cells or the purified OMPs of heterologous M. catarrhalis strains. Furthermore, normal sera collected from healthy children were found to be preferentially reactive with the 60-kDa OMP. The serum-specific IgG, IgA and IgM were respectively detected via immunoblotting in 90%, 85% and 30% of heterologous human sera. This similar immunogenic effectiveness of both OMP-associated liposomal formulations could contribute to the practical use of such formulations in the future in human vaccination. Moreover, the highly cross-reactive 60-kDa OMP seems to be an important antigenic marker of M. catarrhalis, and, as it is responsible for the induction of an antibody-mediated and long-lasting immune response, studying it may partially aid us in understanding the relatively low degree of pathogenicity of the bacterium in immunocompetent individuals.

摘要

外膜蛋白 (OMPs) 是黏液莫拉菌疫苗抗原中最具免疫原性和吸引力的一种,可能诱导保护性免疫反应。本研究旨在确定两种 OMP 相关磷脂酰胆碱 (PC) 脂质体制剂 (OMPs-PC、PC-OMPs) 和两性离子表面活性剂基于的蛋白胶束 (OMPs-Z) 在增强小鼠抗 OMP 系统免疫反应中的有效性。通过 ELISA 和 Western blot 检测免疫后小鼠抗血清中的血清抗-OMP IgG 和 IgA 反应性来评估上述制剂的免疫原性。此外,使用来自人和小鼠的异源血清确定最有效的抗-OMP 反应的交叉反应性。两种蛋白脂质体和蛋白胶束均显示出高免疫原性,并且在抗体滴度方面没有引起任何明显的定量差异,在小鼠抗血清的模式方面也没有引起任何明显的定性差异。免疫后的小鼠抗血清主要识别约 60kDa 的黏液莫拉菌 OMP。该蛋白还被发现是一种高度交叉反应性抗原,与一组由免疫接种整个细胞或异源黏液莫拉菌菌株的纯化 OMP 产生的混合小鼠抗血清相互作用。此外,从健康儿童中收集的正常血清被发现优先与 60kDa OMP 反应。通过免疫印迹分别在 90%、85%和 30%的异源人血清中检测到血清特异性 IgG、IgA 和 IgM。这两种 OMP 相关脂质体制剂的免疫原性有效性相似,这可能有助于将来在人类疫苗接种中实际使用这些制剂。此外,高度交叉反应性的 60kDa OMP 似乎是黏液莫拉菌的一个重要抗原标志物,并且由于它负责诱导抗体介导的持久免疫反应,因此研究它可能有助于我们部分理解该细菌在免疫功能正常个体中的相对低致病性。

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