SURFACE PROTEINS OF MORAXELLA CATARRHALIS

卡他莫拉氏菌的表面蛋白质

• 批准号: 6170003
• 负责人: Eric John Hansen
• 金额: $ 29.18万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-07-01 至 2002-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6170003
• 关键词: Moraxella; active immunization; antibacterial antibody; antibody formation; bacterial antigens; bacterial proteins; bacterial vaccines; bactericidal immunity; collagen; complement; fibronectins; laboratory mouse; membrane proteins; molecular cloning; monoclonal antibody; mucosa; mutant; protein structure function; recombinant proteins; surface antigens; virulence

DESCRIPTION (Adapted from the applicant's abstract): Moraxella (Branhamella) catarrhalis is now acknowledged to be an important cause of otitis media, or middle ear infection, in infants and young children and can also produce disease in the lower respiratory tract. Virtually nothing is known about M. catarrhalis virulence factors or about which surface antigens of this pathogen may be targets for antibodies protective against M. catarrhalis disease. Using an animal model, the applicant has identified two promising vaccine candidates among the surface-exposed proteins of this organism. Both the CopB major outer membrane protein and the UspA surface protein have been shown to be targets for monoclonal antibodies which, when used to passively immunize mice, enhance pulmonary clearance of M. catarrhalis. The applicant has identified a CopB epitope that binds the protective monoclonal antibody described above. In addition, the applicant has discovered that the UspA protein is most similar to the YadA virulence factor of pathogenic Yersinia species. The goal of this grant proposal is to expand upon these findings and investigate these macromolecules as potential vaccine candidates. The first Specific aim involves determination of the functional role of the UspA protein. Specifically, the applicant will use mutant analysis to determine whether this protein is a virulence factor for M. catarrhalis. The second Specific Aim will involve determination of whether CopB- and UspA-derived peptides can induce the synthesis of antibodies that are biologically active against M. catarrhalis. This biological activity will be assessed in bactericidal activity assays and in the pulmonary clearance system. The third Specific Aim involves the use of recombinant forms of the CopB and UspA proteins for testing as experimental vaccinogens. These purified, intact proteins will be tested for their ability to induce the synthesis of biologically active antibodies. The results of these experiments will provide important information about the suitability of CopB and UspA for vaccine development.

描述（改编自申请人的摘要）：莫拉氏菌 (Branhamella) 卡他菌现已被认为是导致 婴儿和幼儿的中耳炎或中耳感染，可以 还会引起下呼吸道疾病。 几乎没有什么是 了解卡他莫拉氏菌毒力因子或表面抗原 这种病原体可能是针对支原体的抗体的目标。 卡他螺旋体病。 使用动物模型，申请人已经确定 该表面暴露蛋白中的两种有前途的候选疫苗 生物。 CopB 主要外膜蛋白和 UspA 表面 蛋白质已被证明是单克隆抗体的靶标，当 用于被动免疫小鼠，增强结核分枝杆菌的肺部清除率。 卡他螺旋体。 申请人已鉴定出与 CopB 结合的表位 如上所述的保护性单克隆抗体。 此外，申请人 发现UspA蛋白与YadA毒力最相似 致病性耶尔森氏菌的因子。 该拨款提案的目标是 扩展这些发现并研究这些大分子 潜在的候选疫苗。 第一个具体目标涉及决心 UspA 蛋白的功能作用。 具体而言，申请人 将使用突变分析来确定该蛋白质是否具有毒力 卡他莫拉氏菌的因子。 第二个具体目标将涉及 确定 CopB 和 UspA 衍生肽是否可以诱导 合成具有抗粘膜炎莫拉氏菌生物活性的抗体。 这种生物活性将在杀菌活性测定中进行评估 和肺部清除系统。 第三个具体目标涉及 使用 CopB 和 UspA 蛋白的重组形式进行测试 实验疫苗原。 这些纯化的、完整的蛋白质将被测试 因为它们能够诱导生物活性抗体的合成。 这些实验的结果将提供重要的信息 CopB 和 UspA 对于疫苗开发的适用性。