Prevention of childhood hearing loss through the development of a vaccine against Moraxella catarrhalis: an understudied cause of otitis media.

 描述(由申请者提供)：与拟议的研究项目一起，培训计划将解决免疫学培训方面的差距，并帮助发展成为独立研究科学家所需的专业技能。免疫学的授课课程将解决基础知识的空白，而与一个由专注于疫苗研究和免疫学的教职员工组成的指导团队的季度会议将有助于指导我的工作。参加以疫苗和免疫学为重点的会议，并与同行讨论当前的免疫学话题，将进一步加强在疫苗研究中取得成功所需的免疫学技能。此外，与指导团队召开季度会议的反馈，参加几个专业发展研讨会和计划，以及在多个会议上展示研究，将有助于发展进行独立研究所需的专业技能。卡他莫拉菌是导致中耳炎和慢性阻塞性肺疾病恶化的主要原因，这两种疾病在全球范围内造成巨大的人类痛苦和经济负担。基于聚合酶链式反应的检测显示严重低估了中耳炎中卡他毛支原体的数量。此外，缺乏对卡他分支杆菌的已确定的保护相关因素，以及缺乏研究这种生物的小组，导致卡他分支杆菌疫苗的开发受到拖延。拟议的项目将通过检查接种OPPA(一种有希望的疫苗抗原)后针对卡他支原体的体液和细胞免疫的作用来解决这一领域的空白。因此，目标1的目标是通过评估在人类和OPPA免疫动物中对OPPA的抗体反应来识别保护性B细胞反应；目标2的目标是在OPPA免疫的小鼠中识别保护性T细胞反应。拟议研究的完成将推进卡特哈里分枝杆菌疫苗领域的发展，并有助于开发预防中耳炎和慢性阻塞性肺病恶化的疫苗。

 DESCRIPTION (provided by applicant): Along with the proposed research project, the training plan will address gaps in immunology training and aid in development of professional skills needed to become an independent research scientist. Didactic courses in immunology will address gaps in basic knowledge, while quarterly meetings with a mentoring team comprised of faculty members with a focus in vaccine research and immunology will help guide my work. Attending vaccine and immunology focused conferences and discussion of current topics in immunology with peers will further strengthen immunology skills needed to be successful in vaccine research. Additionally, feedback from quarterly meetings with a mentoring team, participation in several professional development workshops and programs, and presenting research at multiple conferences will aid in development of professional skills necessary to conduct independent research. Moraxella catarrhalis is a leading cause of otitis media and exacerbations of COPD, two diseases that cause tremendous human suffering and economic burden worldwide. PCR-based detection has revealed severe underestimation of M. catarrhalis in otitis media. Furthermore, the lack of identified correlates of protection against M. catarrhali and lack of groups working on this organism has contributed to the delay in the development of an M. catarrhalis vaccine. The proposed project will address this gap in the field by examining the role of humoral and cellular immunity against M. catarrhalis following vaccination with OppA, a promising vaccine antigen. Therefore, the goal of Aim 1 is to identify protective B cell responses by assessing the antibody response to OppA in humans and OppA-vaccinated animals; the goal of Aim 2 is to identify protective T cell responses in mice immunized with OppA. The completion of the proposed studies will advance the field and aid in development of an M. catarrhalis vaccine to prevent otitis media and exacerbations of COPD.