NTHi Immunity in Young Children

描述（由申请人提供）：非分型流感嗜血杆菌（NTHi）是急性中耳炎（AOM）的主要病因之一，在发展中国家和发达国家的儿童中发病率非常高。本研究的长期目标是更好地了解NTHi的发病机制和鼻咽（NP）定植和AOM后的人类免疫反应，以便制定干预该疾病的策略。我们将前瞻性地收集2至24个月的幼儿的NP、中耳液（MEF）和血清，这些幼儿有中耳炎易发、中耳炎不常见或没有中耳炎。我们建议通过比较清除定植的儿童和长期定植的儿童，来评估对NTHi外膜蛋白P2、P5、P6和OMP26的特异性免疫反应在NP定植清除中的作用。此外，我们将为中耳炎的其他研究人员建立一个前瞻性收集粘膜和血清样本的储存库。本研究的具体目的是：具体目的1：前瞻性地收集中耳炎易发、中耳炎少见或无中耳炎的幼儿的NP分泌物、MEF和血清。特异性目的2：通过比较不同AOM经历的儿童，评估NTHi P2、P5、P6和OMP26特异性免疫应答在AOM清除中的作用；通过比较不同定植经历的儿童，评估NTHi P2、P5、P6和OMP26特异性免疫应答在NP定植清除中的作用。具体目标3：建立一个前瞻性收集的粘膜和血清样本库，用于未来中耳炎的研究。与公共卫生的相关性：该项目特别响应2004年6月8日至9日在美国国立卫生研究院举行的由美国国立卫生研究院和美国国家疾病预防控制研究所组织的关于“中耳炎疫苗：克服进展障碍的建议”的讲习班确定的研究需求。从这些研究中获得的结果将为中耳炎发病机制中涉及的免疫机制提供见解，有助于中耳炎疫苗的开发。

DESCRIPTION (provided by applicant): Nontypable Haemophilus influenzae (NTHi) is one of the major etiological agents of acute otitis media (AOM) which has very high morbidity among children in both developing and developed countries. The long term goal of this research is to better understand NTHi pathogenesis and human immune responses following nasopharyngeal (NP) colonization and AOM, in order to develop strategies for intervention in the disease. We will prospectively collect NP, middle ear fluids (MEF), and sera from young children age 2 to 24 months, who are otitis prone, have infrequent otitis, or remain otitis free. We propose to evaluate the role of specific immune responses to NTHi outer membrane proteins P2, P5, P6, and OMP26 in clearance of NP colonization by comparing children who clear colonization with those who experience prolonged colonization. In addition, we will establish a repository of prospectively collected mucosal and serum samples for other researchers in otitis media. The specific aims of this research are: Specific Aim 1: To prospectively collect NP secretions, MEF, and sera from young children who are otitis prone, have infrequent otitis, or remain otitis free. Specific Aim 2: To evaluate the role of specific immune responses to NTHi P2, P5, P6, and OMP26 in clearance of AOM by comparing children with different AOM experiences and in clearance of NP colonization by comparing children with different colonization experiences. Specific Aim 3: To establish a repository of prospectively collected mucosal and serum samples for future research in otitis media. Relevance to Public Health: This project is specifically responsive to research needs identified at an NIAID and NIDCD-organized workshop held at the NIH on 8-9 June 2004 on "Vaccines for Otitis Media: Proposals for Overcoming Obstacles to Progress." The results gained from these studies will provide insight to the immune mechanisms involved in the pathogenesis of otitis media aid in the development of a vaccine for otits media.