SURFACE PROTEINS OF MORAXELLA CATARRHALIS

描述(改编自申请者的摘要)：莫拉氏菌 (Branhamella)卡特拉病现在被认为是 婴幼儿中耳炎或中耳感染 也会在下呼吸道产生疾病。几乎没有什么是 已知卡他毛杆菌毒力因子或哪些表面抗原 可能是M。 卡特哈里斯病。使用动物模型，申请者已经识别出 在该病毒的表面暴露蛋白中有两个很有希望的候选疫苗 有机体。CopB主要外膜蛋白和USPA表面 蛋白质已被证明是单抗的靶标，当 用于被动免疫小鼠，增强M。 卡特哈利斯。申请人已经确定了一个CopB表位，它结合了 上述保护性单抗。此外，申请人 已经发现UspA蛋白与雅达毒力最相似 耶尔森氏菌致病因子。这项拨款提案的目标是 在这些发现的基础上扩展并研究这些大分子 潜在的疫苗候选者。第一个具体目标涉及决心 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质是否是毒力 卡氏支原体的致病因子。第二个具体目标将涉及 确定CopB和USPA衍生的多肽是否能诱导 抗卡他毛虫生物活性抗体的合成。 这种生物活性将在杀菌活性分析中进行评估。 在肺清除系统中。第三个具体目标涉及 利用重组形式的CopB和USPA蛋白检测AS 实验性的疫苗原。这些纯化的、完整的蛋白质将被测试 因为它们有能力诱导合成生物活性抗体。 这些实验的结果将提供关于 CopB和USPA在疫苗开发中的适用性。

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.