NTHi Immunity in Young Children

描述(申请人提供)：非分型流感嗜血杆菌(NTHi)是急性中耳炎(AOM)的主要病原体之一，在发展中国家和发达国家的儿童中都有很高的发病率。这项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个月大的幼儿的NP、中耳液(MEF)和血清，这些幼儿易患中耳炎、不常患中耳炎或保持无中耳炎。我们建议通过比较明确定植的儿童和经历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清除NP定植中的作用。此外，我们将建立一个前瞻性收集的粘膜和血清样本的资料库，供其他中耳炎研究人员使用。这项研究的具体目标是：特定目标1：前瞻性地收集易患中耳炎、少见中耳炎或保持无中耳炎的幼儿的NP分泌物、MEF和血清。具体目的2：通过比较不同AOM经历的儿童和不同定植经历的儿童，评价对NTHi P2、P5、P6和OMP26的特异性免疫应答在清除AOM中的作用和对NP定植的清除作用。具体目标3：建立一个前瞻性收集的粘膜和血清样本的资料库，用于未来中耳炎的研究。与公共卫生的相关性：该项目具体回应了NIAID和NIDCD于2004年6月8日至9日在NIH举办的关于“耳炎媒体疫苗：克服进展障碍的建议”的研讨会上确定的研究需求。这些研究的结果将为深入了解中耳炎发病机制提供帮助，有助于研制中耳炎疫苗。

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.