NATURAL HISTORY STUDIES: GBS AND PNEUMOCOCCAL INFECTION

自然史研究：GBS 和肺炎球菌感染

• 批准号: 3096836
• 负责人: BARRY GRAY
• 金额: $ 63.51万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 1983
• 资助国家: 美国
• 起止时间: 1983-07-01 至 1993-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3096836
• 关键词: Streptococcus agalactiae; Streptococcus infection; Streptococcus pneumoniae; bactericidal immunity; communicable disease transmission

The objective of this renewal program is to further explore the natural history of infections caused by Streptococcus pneumoniae, group B streptococcus (GBS), and Hemophilus influenzae type b. These three pathogens account for most serious bacterial infection in infants and children and remain significant causes of disease in otherwise healthy young women (GBS puerpural infections) and in aging adults (the pneumococcus). They share many biological and immunological features, and their disease potential has continued to be high, despite advances in antibiotic therapy and development of vaccines. Satisfactory modes of prevention have yet to be realized. This program will focus upon key aspects of host- parasite relationships that may help explain the development of disease and suggest new approaches to its prevention The Core Project provides clinical support for the entire program. While continuing to yield important epidemiologic information through new and ongoing clinical studies, it provides essential patient materials, bacterial isolates, and epidemiological data from well defined patient populations. Seroepidmeiological investigations Project 1 will make use of these materials to more precisely define "protection" in immunological terms. Its studies will evaluate functional (opsonophagocytic) antibody with respect to measured properties, critically examining the roles of avidity and blocking by specific IgA antibodies. Studies of antibody functions other than opsonization will focus upon the activation of platelets and neutrophils in vitro and in acute disease. The immunochemistry of GBS polysaccharides will be studied in Project 2. The similarities between GBS antigens and glycoconjugates of the human host will be examined in relation to colonization and disease. The molecular basis for these similarities will be studied with modern NMR techniques, monoclonal antibodies, and chemically modified GBS antigens: The concept of "virulence" will be examined with respect to biological properties of the bacteria and their polysaccharide capsules. Project 3 will study the surface protein antigens of the pneumococci to develop a protein typing system and to evaluate the possible application of surface proteins as candidate vaccines. The epidemiology of surface protein--will be studied in correlation with the human antibody response to pneumococcal colonization and disease.

该更新计划的目的是进一步探索 肺炎链球菌引起的感染的自然史， B 组链球菌 (GBS) 和 b 型流感嗜血杆菌。 这三种病原体是最严重的细菌感染 在婴儿和儿童中，仍然是疾病的重要原因 在其他方面健康的年轻女性（GBS 脓疱感染）和 老年人（肺炎球菌）。 他们有许多共同的生物学和 免疫学特征，其疾病潜力仍在持续 尽管抗生素治疗和开发取得了进步，但仍然很高 疫苗。 尚待建立令人满意的预防模式 意识到了。 该计划将重点关注主办方的关键方面 寄生关系可能有助于解释 疾病并提出新的预防方法 核心项目为整个项目提供临床支持。 在继续提供重要流行病学信息的同时 通过新的和正在进行的临床研究，它提供了必要的 患者材料、细菌分离物和流行病学数据 来自明确定义的患者群体。 血清流行病学 调查项目 1 将利用这些材料来更多 用免疫学术语精确定义“保护”。 其研究 将评估功能性（调理吞噬）抗体 根据测量的属性，批判性地检查亲和力的作用 并通过特异性 IgA 抗体进行阻断。 抗体研究 除调理作用以外的功能将集中于激活 体外和急性疾病中的血小板和中性粒细胞。 GBS多糖的免疫化学研究将在 项目2. GBS抗原与 将检查人类宿主的糖缀合物 定植和疾病。 这些的分子基础 将使用现代核磁共振技术、单克隆技术来研究相似性 抗体和化学修饰的 GBS 抗原：概念 将根据生物学特性检查“毒力” 细菌及其多糖胶囊。 项目3将研究表面蛋白抗原 肺炎球菌开发蛋白质分型系统并评估 表面蛋白作为候选疫苗的可能应用。 表面蛋白的流行病学--相关研究 人类抗体对肺炎球菌定植的反应 疾病。