Recurrent otitis media and COPD: immunity and vaccines

中耳炎导致巨大的发病率，并且在美国每年的直接医疗保健费用估计为30亿美元。慢性阻塞性肺病（COPD）是美国第四大最常见的死亡原因。COPD中的细菌感染导致显著的发病率和死亡率。在COPD中引起中耳炎和呼吸道感染的三种最常见的细菌病原体中的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COPD成人中耳炎和呼吸道感染的疫苗将对降低这些环境中的死亡率、预防发病率和降低医疗保健成本产生重要影响。本计画计画提出研究将阐明NTHI与M之特定抗原之免疫反应。粘膜炎。我们的假设是，NTHI和M引起的呼吸道感染的模式。儿童和成人的卡他病取决于对生物体的特异性表面抗原的免疫应答。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将表征人类T细胞对蛋白质P6的反应的作用，这是一种有希望的疫苗抗原，将通过对人类仔细定义的样本进行研究来确定。项目3将重点研究M.卡他，NOS作为粘附素的作用和对LOS分子决定簇的人体免疫应答。一个行政/统计核心将协调该方案，并为每个项目提供统计专门知识。自NTHI和M.卡他炎是人类独有的病原体，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COPD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.