Immunity directed against MSP 2 during anaplasmosis

无形体病期间针对 MSP 2 的免疫

• 批准号: 6741510
• 负责人: JEFFREY R ABBOTT
• 金额: $ 4.64万
• 依托单位: WASHINGTON STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-05-01 至 2005-01-01
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6741510
• 关键词: B lymphocyte; Rickettsiales; Rickettsiales disease; antibacterial antibody; antibody titering; bacterial antigens; bacterial proteins; bacterial vaccines; complementary DNA; cow; helper T lymphocyte; immunotherapy; leukocyte activation /transformation; membrane proteins; microorganism immunology; molecular cloning; nonhuman therapy evaluation; recombinant proteins; ticks; vaccine development

DESCRIPTION (provided by applicant): Agents of the tribe Ehrlichiae cause a variety of tick-borne diseases in both humans and animals. Many of these agents persist in the host thus acting as potential reservoirs for further spread of disease. Anaplasma marginale is closely related genetically (16S rRNA) with E. phagocytophila, the causative agent of human granulocytic ehrlichiosis (HGE). Indeed, both organisms express antigenically variant outer membrane proteins, major surface protein-2 (MSP-2) that share significant amino acid sequence conservation characterized by highly conserved N and C terminal regions and a central, hydrophilic, hypervariable region. Levels of rickettsemia during persistent anaplasmosis are approximately two orders of magnitude less than rickettsemia levels during acute infection and do not result in clinical disease. We hypothesize that the control of rickettsemia to levels significantly below those observed during acute clinical anaplasmosis is due to a memory CD4+ Th-cell response to conserved epitopes on MSP-2 that enhance variant specific B cell responses directed against the hypervariable region. The results of this research will provide insight into means of developing outer membrane protein-based vaccines against A. marginale and other ehrlichial organisms that cause disease in animals and humans, especially the closely related agent of HGE, E. phagocytophila

描述（由申请人提供）：埃里希体族病原体引起 人类和动物的各种蜱传疾病。许多这些 病原体在宿主中持续存在，从而充当进一步的潜在储存库。 疾病的传播。边缘无形体在遗传上密切相关（16 S rRNA）与E.嗜吞噬细胞菌，人粒细胞 埃立克体病（HGE）。事实上，这两种生物体都表达抗原性变异的外 膜蛋白，主要表面蛋白-2（MSP-2）， 以高度保守的N和C为特征的氨基酸序列保守性 末端区和中心的亲水性高变区。水平 持续无形体病期间的立克次体约为两个数量级， 在急性感染期间的幅度低于立克次体水平， 导致临床疾病。我们假设控制立克次体， 水平显著低于急性临床无形体病期间观察到的水平 是由于记忆性CD 4 + Th细胞对MSP-2上保守表位的应答， 增强针对高变的变异体特异性B细胞应答 地区这项研究的结果将提供洞察手段， 开发基于外膜蛋白的抗A.边缘和 其他在动物和人类中引起疾病的埃里希体生物， 尤其是与HGE密切相关的病原体E.嗜吞噬细胞