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: 3821980
• 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/3821980
• 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; leukocyte activation /transformation; linkage mapping; lipopolysaccharides; microorganism immunology; monoclonal antibody; radioimmunoassay; radiotracer; virulence; zoonosis

Immunogenic and pathogenic subfractions of Coxiella burnetii, the etiological agent of Q fever, are being studied in animals and humans to evaluate humoral and cellular mechanisms of immunity. A. Mice. Phase I whole cell and chloroform-methanol residue vaccines prepared by Salk Institute protected A/J mice from lethal challenge by aerosol and intraperitoneal routes. The aerosol route did not induce antibodies against phase I lipopolysaccharide, yet marked increases of antibody against surface proteins were measured. This surprising result contradicts the traditional view that antibodies against LPSI are a measure of immunity. Therefore protein subunit vaccines may be efficacious. The resistance of C. burnetii to formalin treatment has led to the evaluation of gamma (60Co) dose response to inactivate residual viable organisms in vaccine preparations. One thousand kilo Rads are required to kill 3.8X1010 organisms per ml of medium for the effective sterilization of vaccines and reagents. B. Immune Modulation. The immune suppressive complex (ISC) virulence factor was expressed differently among 9 strains of C. burnetii. Strains expressing only smooth LPSI carried the most potent ISC. None of the strains with only rough LPSII expressed the ISC. However, one strain isolated from heart valve did not expressed the ISC although it contained both smooth and rough LPS chemotypes. C. Antigen Shift. Immuno-gold labeling techniques were used to verify that the different morphologic forms of C. burnetii express different antigenic surfaces. Also the endospore within the large cells were not detected by any antibody preparation. D. Seroepidemiology. A case controlled study to determine the incidence and risk for acquisition of Q fever has revealed that parturient cats are significant in outbreaks of atypical pneumonia. The role of cats in the spread of Q fever to humans may impact significantly of this zoonosis. E. Significance. This project identified a non-toxic efficacious Q fever vaccine, derived a gamma irradiation protocol to kill residual C. burnetii, described different components of the ISC and the distribution among strains, verified antigenic shift among cell variants and defined the role of parturient cats in the spread of Q fever.

Coxiella burnetii的免疫原性和致病性亚分支， Q发烧的病因学剂正在动物中研究， 人类评估体液和细胞机制 免疫。 A.老鼠。 I期全细胞和氯仿 - 甲醇 Salk Institute制备的残留疫苗保护A/J小鼠 来自气溶胶和腹膜内路线的致命挑战。 这 气溶胶路线没有诱导I期抗体 脂多糖，但标志着抗体的增加 测量表面蛋白。 这个令人惊讶的结果 与传统观点相矛盾，即对LPSI的抗体是一种 衡量免疫力。 因此蛋白质亚基疫苗可能是 有效。 C. burnetii对福尔马林治疗的阻力 导致对伽马（60co）剂量反应的评估 在疫苗制剂中灭活残留的生物体。 一 每毫升需要杀死3.8x1010生物需要千公斤 有效疫苗灭菌的培养基和 试剂。 B.免疫调节。 免疫抑制 复合物（ISC）毒力因子在9中的表达方式不同 C. burnetii的菌株。 仅表达光滑LPSI的菌株 携带最有效的ISC。 没有一个粗糙的菌株 LPSII表示ISC。 但是，一个菌株从心脏隔离 阀没有表达ISC，尽管它既包含平滑 和粗糙的LPS化学型。 C.抗原转移。 免疫金 标签技术用于验证是否不同 C. burnetii的形态形式表达不同的抗原 表面。 大细胞内的内孢子也不是 通过任何抗体制剂检测到。 D. SeroepideMiology。 一个 病例对照研究，以确定发生率和风险 Q发烧的获取表明猫是 非典型肺炎的暴发意义重大。 猫的角色 在Q发烧传播中，人类可能会显着影响 这个动物病。 E.意义。 该项目确定了无毒的 有效的Q发烧疫苗，得出伽马辐照方案 杀死残留的C. burnetii，描述了的不同组成部分 ISC和菌株之间的分布，经过验证的抗原移位 在细胞变体中，并定义了分离猫在 Q热的传播。