Recurrent otitis media and COPD: immunity and vaccines

慢性阻塞性肺疾病（COPD）是美国第四大最常见的死亡原因。慢性阻塞性肺疾病（COPD）的细菌感染导致了大量的发病率和死亡率。在引起慢性阻塞性肺病中耳炎和呼吸道感染的三种最常见的细菌病原体中，有两种是不可分型的流感嗜血杆菌（NTHI）和卡他莫拉菌。开发预防成人慢性阻塞性肺病患者中耳炎和呼吸道感染的疫苗将对降低死亡率、预防发病率和降低这些环境中的医疗保健成本产生重要影响。本项目拟开展研究，阐明NTHI和卡他氏分枝杆菌对特异性抗原的免疫反应。我们的假设是，儿童和成人由NTHI和卡塔林分枝杆菌引起的呼吸道感染的模式取决于对生物体特定表面抗原的免疫反应。该项目的目标将通过一个多学科研究小组的努力来实现，该小组将合作开展三个相互关联的项目。项目1将描述人类T细胞对P6蛋白反应的作用，P6蛋白是一种有希望的疫苗抗原，将通过仔细定义的人类样本进行研究来确定。项目3将重点研究卡他氏芽胞杆菌低脂寡糖（LOS）的抗原性特征，NOS作为粘附素的作用以及人类对LOS分子决定因素的免疫反应。行政/统计核心将协调该方案并为每个项目提供统计专门知识。由于NTHI和M. catarrhalis完全是人类病原体，因此重点放在阐明人类免疫反应上。拟议的研究将推进疫苗开发领域，以预防慢性阻塞性肺病中耳炎和呼吸道感染。

Otitis media leads to enormous morbidity and to direct annual healthcare costs estimated to be $3 billion in the U.S. Chronic obstructive pulmonary disease (COPD) is the fourth most common cause of death in the U.S. Bacterial infection in COPD causes substantial morbidity and mortality. Two of the three most common bacterial pathogens to cause otitis media and respiratory tract infections in COPD are non-typeable Haemophilus influenzae (NTHI) and Moraxella catarrhalis. The development of vaccines to prevent otitis media and respiratory tract infections in adults with COPD would have important impact in reducing mortality, preventing morbidity and reducing healthcare costs in these settings. This program project proposes studies which will elucidate the immune response to specific antigens of NTHI and M. catarrhalis. Our hypothesis is that the pattern of respiratory tract infections due to NTHI and M. catarrhalis in children and adults depends on the immune response to specific surface antigens of the organisms. The aims of the project will be accomplished through the efforts of a multi-disciplinary research team which will collaborate to carry out three interrelated projects. Project 1 will characterized the role of human T cell responses to protein P6, a promising vaccine antigen will be determined through studies with carefully defined samples from humans. Project 3 will focus on antigenic characterization of the lipooligosaccharide (LOS) of M. catarrhalis, the role of NOS as an adhesin and the human immune response to determinants on the LOS molecule. An Administrative/Statistical Core will coordinate the program and provide statistical expertise to each of the projects. Since NTHI and M. catarrhalis are exclusively human pathogens, a strong emphasis is placed on elucidation of the human immune response. The proposed studies will advance the field of vaccine development to prevent otitis media and respiratory tract infections in COPD.