SURFACE PROTEINS OF MORAXELLA CATARRHALIS

卡他莫拉氏菌的表面蛋白质

• 批准号: 2672365
• 负责人: Eric John Hansen
• 金额: $ 26.98万
• 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 2001-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2672365
• 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）：摩拉氏菌 （Branhamella）卡塔哈里斯现在被认为是 婴儿和幼儿中耳炎或中耳感染，可以 还会在下呼吸道中产生疾病。 几乎什么都没有 有关卡他甲菌的毒力因子或哪种表面抗原已知 该病原体可能是针对M的抗体保护的靶标。 卡塔哈里斯病。 使用动物模型，申请人已经确定 在表面暴露的蛋白质中，有两个有希望的疫苗候选物 生物。 COPB主要外膜蛋白和USPA表面既有 蛋白质已被证明是单克隆抗体的靶标的 用于被动免疫小鼠，增强M的肺清除率。 卡塔哈里斯。 申请人已经确定了一个结合的COPB表位 上述保护性单克隆抗体。 此外，申请人 已经发现USPA蛋白与YADA毒力最相似 病原耶尔森氏症的因素。 该赠款提议的目标是 扩展这些发现并研究这些大分子 潜在的疫苗候选物。 第一个特定目的涉及决心 USPA蛋白的功能作用。 具体来说，申请人 将使用突变分析来确定该蛋白是否是毒力 卡塔哈里斯菌的因素。 第二个特定目标将涉及 确定COPB和USPA衍生的肽是否可以诱导 对抗原分枝杆菌具有生物活性的抗体的合成。 这种生物学活性将在杀菌活性测定中进行评估 并在肺通关系统中。 第三个特定目标涉及 使用重组形式的COPB和USPA蛋白作为测试 实验性疫苗。 这些纯化，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有关有关的重要信息 COPB和USPA对疫苗开发的适用性。