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首页> 外文学位 >Pilin-based vaccine design for Neisseria gonorrhoeae: Analysis of murine immune responses to the conserved and hypervariable regions of PilE.
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Pilin-based vaccine design for Neisseria gonorrhoeae: Analysis of murine immune responses to the conserved and hypervariable regions of PilE.

机译：淋病奈瑟氏球菌基于皮林的疫苗设计：鼠对PilE保守和高变区的免疫反应分析。

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摘要

PilE is the primary subunit of type IV pili from Neisseria gonorrhoeae , and contains a surface-exposed hypervariable region that has prevented development of a pilin-based vaccine. We have created a 3-D structure-based antigen by replacing the hypervariable region of PilE with an aspartate-glutamine linker chosen from the sequence of Pseudomonas aeruginosa PilA. We then characterized murine immune responses to this novel protein to determine if HE conserved regions could serve as a vaccine candidate. The control PilE protein elicited strong T cell-dependent B cell responses that are specific to epitopes in both the hypervariable deletion and control proteins. In contrast, the hypervariable deletion protein was unable to elicit an immune response in mice, suggesting that in the absence of the hypervariable region, the conserved regions of PilE alone are not sufficient for antibody production. Further analysis of these PilE proteins with suppressor cell assays showed that neither suppresses T or B cell responses, and flow cytometry experiments suggested they do not exert suppressor effects by activating T regulatory cells. Our results definitively show that the hypervariable region of PilE is required to activate immune responses to pilin, whereas the conserved regions are unusually nonimmunogenic. In addition, we show that both hypervariable and conserved regions of pilin are not suppressive, suggesting that PilE does not cause the decrease in T cell populations observed during gonococcal cervicitis. This work describes the creation of a novel PilE protein using the conserved regions of PilE. In this dissertation I have not only demonstrated that the HE conserved region would not be an appropriate vaccine component, but have also shown that regions of a bacterial protein can be immuno-silent without homology to mammalian proteins.
机译：PilE是淋病奈瑟氏球菌的IV型菌毛的主要亚基，其表面暴露的高变区阻止了基于菌毛蛋白的疫苗的开发。我们通过用选自铜绿假单胞菌PilA序列的天冬氨酸-谷氨酰胺接头取代PilE的高变区，创建了基于3-D结构的抗原。然后，我们表征了对该新蛋白的鼠类免疫反应，以确定HE保守区是否可以作为候选疫苗。对照PilE蛋白引起强T细胞依赖性B细胞应答，其对高变缺失和对照蛋白中的表位具有特异性。相反，高变缺失蛋白不能在小鼠中引发免疫反应，表明在没有高变区的情况下，仅PilE的保守区不足以产生抗体。用抑制细胞试验对这些PilE蛋白进行进一步分析表明，它们都不能抑制T细胞或B细胞反应，流式细胞仪实验表明它们不能通过激活T调节细胞发挥抑制作用。我们的结果明确表明，激活PilE的免疫反应需要PilE的高变区，而保守区则具有非免疫原性。此外，我们表明，菌毛蛋白的高变区和保守区都没有抑制作用，表明PilE不会导致淋球菌性宫颈炎期间观察到的T细胞数量减少。这项工作描述了使用PilE的保守区域创建新的PilE蛋白。在本论文中，我不仅证明了HE保守区不是合适的疫苗成分，而且还表明了细菌蛋白区域可以是免疫沉默的，而与哺乳动物蛋白没有同源性。

著录项

  • 作者

    Hansen, Johanna Kay.;

  • 作者单位

    The University of Wisconsin - Madison.;

  • 授予单位 The University of Wisconsin - Madison.;
  • 学科 Biology Microbiology.; Chemistry Biochemistry.
  • 学位 Ph.D.
  • 年度 2007
  • 页码 168 p.
  • 总页数 168
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 微生物学;生物化学;
  • 关键词

  • 入库时间 2022-08-17 11:40:13

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