SURFACE PROTEINS OF MORAXELLA CATARRHALIS

性状（改编自申请人摘要）：莫拉菌属 （布兰汉菌）卡他现在被认为是一个重要的原因， 中耳炎或中耳感染，并且可以 也会引起下呼吸道疾病。 事实上， 了解M。卡他毒力因子或关于哪些表面抗原 这种病原体的可能是针对M. 卡他病 使用动物模型，申请人已确定 这两个有希望的疫苗候选人之间的表面暴露的蛋白质， 有机体 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M. 粘膜炎。 申请人已经鉴定了结合C 0 pB的CopB表位。 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。 这项拨款提案的目的是 为了扩展这些发现并研究这些大分子， 潜在的疫苗候选人 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这种蛋白质是否具有毒性 因子M。粘膜炎。 第二个具体目标将涉及 确定CopB-和UspA-衍生肽是否可以诱导 合成对M.粘膜炎。 将在杀菌活性测定中评估该生物活性 和肺清除系统。 第三个具体目标涉及 使用重组形式的CopB和UspA蛋白作为 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用于疫苗开发的适用性。

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.