IMMUNOLOGIC PROPERTIES OF COXIELLA BURNETII (Q FEVER) VACCINE

伯内特柯克斯体 (Q FEVER) 疫苗的免疫学特性

• 批准号: 3960468
• 负责人: J C WILLIAMS
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3960468
• 关键词: Q fever; antiserum; bacterial antigens; bacterial cytopathogenic effect; bacterial polysaccharides; bacterial vaccines; bactericidal immunity; cellular immunity; cellular oncology; chemical structure function; disease /disorder model; electron microscopy; enzyme linked immunosorbent assay; gel electrophoresis; histochemistry /cytochemistry; human tissue; humoral immunity; immune tolerance /unresponsiveness; immunodiffusion; immunoelectrophoresis; immunofluorescence technique; immunological substance; immunosuppression; indomethacin; leukocyte activation /transformation; linkage mapping; lipopolysaccharides; macrophage; microorganism immunology; monoclonal antibody; prostaglandin E; radioimmunoassay; radiotracer; virulence

Immunogenic and pathogenic subfractions of Coxiella burnetii, the etiological agent of Q fever, are being studied in animals and in man in order to evaluate humoral and cellular mechanisms of pathogenesis. A. Mice. Sensitive (A/J) mice develop T-cell suppression and produce anti-lipopolysaccharide (LPS) antibodies late (35 days) in a low dose phase I infection; whereas, resistant (C57BL/6J) mice do not develop T-cell suppression and they produce anti-LPS antibodies early (21 days). Some phase I cells possess an immune suppressive complex (ISC) which consists of three separable components that may not be active alone but components 1 & 2 are required for activity, and component 3 anchors 1 & 2 to the cell surface. The biological response modification (BRM) induced by the ISC favors the growth of C. burnetii while not debilitating the hosts' response to other pathogenic agents. The ISC induces T- and B-cell antigen-specific suppressors which bind antigen. A T-cell suppresses the ConA response while a B-cell suppresses responses to antigen, but in concert these cells participate in an antigen-dependent suppressor circuit. B. Subunit vaccine. Major outer membrane proteins were identified and chromosomal DNA encoding at least 5 proteins were cloned and expressed in Escherichia coli. The structure of one of these proteins may be regulated by the acid environment of the phagolysosome thus conferring acidophilic properties to the C. burnetii cell surface. A new pahse I subunit vaccine designated as cholorform-methanol residue (CMR) produced by the Salk Institute will enter preclinical trials in September 1986. Previously, we showed that the CMR vaccine was non-toxic and efficacious in animals. Significance: The objectives of this project are to define the genetic basis of susceptibility to infection in the mouse model, to characterize components of the ISC, to develop a new recombinant subunit vaccine, and test the safety and efficacy of the CMR vaccine. Accomplishment of these objectives will allow us to produce recombinant vaccine against Q fever and test the Biological Respose Modification in model systems.

Coxiella burnetii的免疫原性和致病性亚分支， Q发烧的病因学因动物和人正在研究 为了评估发病机理的体液和细胞机制。 一个。 老鼠。 敏感（A/J）小鼠会形成T细胞抑制并产生 低剂量期的抗脂多糖（LPS）抗体晚期（35天） 我感染；而耐药（C57BL/6J）小鼠不发展T细胞 抑制作用和它们产生抗LPS抗体（21天）。 一些 I期细胞具有免疫抑制复合物（ISC），由 三个可能不单独活跃的可分离组件，但组件1＆ 活动需要2，而组件3将1和2锚定在单元格上 表面。 ISC诱导的生物反应修饰（BRM） 有利于C. burnetii的增长，而不会使宿主的反应使人衰弱 到其他致病剂。 ISC诱导T-和B细胞抗原特异性 结合抗原的抑制剂。 T细胞抑制CONA响应 而B细胞抑制了对抗原的反应，但在协调一时 参与抗原依赖性抑制器电路。 B.亚基 疫苗。 鉴定出主要的外膜蛋白和染色体DNA 克隆至少5种蛋白质的编码，并在大肠杆菌中表达 大肠杆菌。 这些蛋白质之一的结构可以由酸调节 吞噬体的环境，从而将嗜酸性特性赋予 C. burnetii细胞表面。 新的Pahse I亚基疫苗被指定为 Salk Institute生产的胆固醇 - 甲醇残基（CMR）将进入 1986年9月的临床前试验。以前，我们证明了CMR 疫苗在动物中无毒且有效。 意义： 该项目的目标是定义 在鼠标模型中感染感染的敏感性，以表征组件 ISC开发新的重组亚基疫苗，并测试 CMR疫苗的安全性和功效。 实现这些目标 将使我们能够针对Q发烧生产重组疫苗并测试 模型系统中的生物响应修饰。