HAEMOPHILUS INFLUENZAE OTITIS MEDIA--PROTECTIVE IMMUNITY

流感嗜血杆菌中耳炎--保护性免疫

• 批准号: 3131983
• 负责人: Stephen J. Barenkamp
• 金额: $ 16.23万
• 依托单位: SAINT LOUIS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-09-01 至 1995-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3131983
• 关键词: Bordetella pertussis; Haemophilus influenzae; active immunization; antibacterial antibody; bacterial antigens; bacterial proteins; bactericidal immunity; chinchilla; disease /disorder model; genetic strain; hemagglutinin; host organism interaction; human tissue; organ culture; otitis media

Otitis media and other illnesses caused by nontypable Haemophilus influenzae (NTHI) remain significant health problems for children in this country and elsewhere in the world. Efforts to develop vaccines for the prevention of disease are being made by a number of investigators. We have identified a family of high molecular weight outer membrane proteins nontypable Haemophilus influenzae which are major targets of host antibody both in children convalescing from nontypable Haemophilus acute otitis media and in normal adults who are naturally immune to disease. In an effort to further characterize these proteins, we have cloned, expressed, and sequenced two genes from a prototype NTHI strain which encode high molecular weight proteins identical to those recognized by the human sera. The nucleotide sequence data from these two cloned genes and additional immunologic and morphologic data suggest that the NTHI high, molecular weight proteins are structural and possibly functional analogues of the filamentous hemagglutinin protein of Bordetella Pertussis. Filamentous hemagglutinin is an important adherence factor and protective antigen of Bordetella pertussis. Our hypothesis is that the high molecular weight serve a similar functional role for NTHI. We will use several in vitro and in vivo techniques to further characterize these high molecular weight proteins and define their role in bacterial adhesion and the role of antibody directed against them in host protection. Specifically, we will perform absorption experiments to determine the contribution of antibody directed against the high molecular weight proteins to the bactericidal activity present in human sera. We will prepare antisera against purified high molecular weight proteins and assay the resulting antisera in functional assays which include bactericidal assays in vitro and animal protection experiments in the chinchilla otitis media in vivo. Active immunization experiments with purified proteins will also be performed in the animal model. We will assess the contribution of these high molecular weight proteins to the adherence of NTHI using an adenoidal organ culture model. Finally, we will further examine the relationship between the NTHI high molecular weight proteins and the filamentous hemagglutinin protein of Bordetella pertussis using several Bordetella pertussis specific adherence assays. The resulting information should be of value not only for enhancing our understanding of the biology of NTHI and but also may be of importance in efforts to develop vaccines protective against infection caused by these organisms.

中耳炎培养基和其他由不可抑制的血友病引起的疾病 流感（nthi）在这方面仍然是儿童的重大健康问题 国家和世界其他地方。 为开发疫苗的努力 许多研究人员正在预防疾病。 我们有 确定了一个高分子量外膜蛋白的家族 不可用的嗜血杆菌流感，这是宿主抗体的主要靶标 这两者都在因不可抑制的嗜血性急性中耳炎而康复的儿童中 媒体和正常成年人自然免受疾病的影响。 在 为了进一步表征这些蛋白质的努力，我们已经克隆，表达， 并从编码高的原型NTHI菌株中测序了两个基因 分子量蛋白与人类血清识别的蛋白相同。 来自这两个克隆基因的核苷酸序列数据和其他 免疫学和形态学数据表明，NTHI高分子 重量蛋白是结构性的，可能是功能类似物 百日草的丝状血凝素蛋白。 丝状 血凝素蛋白是重要的依从性因素和保护性抗原 Bordetella百日咳。 我们的假设是高分子量 在NTHI中发挥类似的功能作用。 我们将使用几个体外， 体内技术以进一步表征这些高分子量 蛋白质并定义其在细菌粘附中的作用和 抗体针对宿主保护。 具体来说，我们会的 执行吸收实验以确定抗体的贡献 针对杀菌的高分子量蛋白针对高分子量蛋白 人类血清中存在的活动。 我们将准备安提塞拉抗纯化 高分子量蛋白，并在 功能分析，包括体外和动物的杀菌测定 在体内龙猫中耳炎的保护实验。 积极的 纯化蛋白质的免疫实验也将在 动物模型。 我们将评估这些高分子的贡献 使用腺体器官培养 模型。 最后，我们将进一步研究NTHI之间的关系 高分子量蛋白和丝状血凝素蛋白 百日咳bordetella buldetella bordetella distect 测定。 结果信息不仅应具有 增强我们对NTHI生物学的理解，但也可能是 在开发防止感染的疫苗保护性的努力方面的重要性 由这些生物引起。