Recurrent otitis media and COPD: immunity and vaccines

复发性中耳炎和慢性阻塞性肺病：免疫和疫苗

• 批准号: 6757242
• 负责人: Timothy F Murphy
• 金额: $ 61.58万
• 依托单位: STATE UNIVERSITY OF NEW YORK AT BUFFALO
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-08-15 至 2006-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6757242
• 关键词: Haemophilus influenzae; Haemophilus influenzae vaccines; Moraxella; bacterial vaccines; chronic obstructive pulmonary disease; microorganism immunology; otitis media; vaccine development

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.

在美国，中耳炎导致巨大的发病率和每年直接医疗费用，估计达 30 亿美元。慢性阻塞性肺病 (COPD) 是美国第四大常见死因。COPD 中的细菌感染导致大量发病率和死亡率。引起 COPD 中耳炎和呼吸道感染的三种最常见细菌病原体中的两种是不可分型流感嗜血杆菌 (NTHI) 和卡他莫拉菌。开发预防慢性阻塞性肺病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费用产生重要影响。该计划项目提出的研究将阐明对 NTHI 和粘膜炎莫拉氏菌特定抗原的免疫反应。我们的假设是，儿童和成人中 NTHI 和卡他莫拉氏菌引起的呼吸道感染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多学科研究团队的努力来实现，该团队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 反应的作用，蛋白质 P6 是一种有前途的疫苗抗原，将通过对来自人类的仔细确定的样本进行研究来确定。项目 3 将重点研究卡他莫拉氏菌脂寡糖 (LOS) 的抗原特性、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/统计核心将协调该计划并为每个项目提供统计专业知识。由于 NTHI 和粘膜炎莫拉氏菌完全是人类病原体，因此重点强调阐明人类免疫反应。拟议的研究将推进预防慢性阻塞性肺病中耳炎和呼吸道感染的疫苗开发领域。

项目成果

Biofilm formation by nontypeable Haemophilus influenzae: strain variability, outer membrane antigen expression and role of pili.

不可用嗜血杆菌的生物膜形成：菌株变异性，外膜抗原表达和pili的作用。

• DOI: 10.1186/1471-2180-2-7
• 发表时间: 2002-04-15
• 期刊: BMC MICROBIOLOGY
• 影响因子: 4.2
• 作者: Murphy, Timothy F.;Kirkham, Charmaine
• 通讯作者: Kirkham, Charmaine

Tracking the tissue distribution of marker dye following intranasal delivery in mice and chinchillas: a multifactorial analysis of parameters affecting nasal retention.

• DOI: 10.1016/s0264-410x(02)00247-5
• 发表时间: 2002-08
• 期刊: Vaccine
• 影响因子: 5.5
• 作者: Anju Visweswaraiah;L. Novotny;Erik J Hjemdahl-Monsen;L. Bakaletz;Y. Thanavala