Analysis of A Baumannii Capsule as a Vaccine Candidate

描述(由申请人提供)： 鲍曼氏酸杆菌是一种革兰氏阴性杆菌，最初被认为会引起医疗保健相关的感染。最近，伊拉克/科威特/阿富汗的经验重申了鲍曼不动杆菌在造成受伤战斗人员感染方面的重要性。此外，鲍曼不动杆菌多重耐药和泛耐药菌株的流行正在增加，将我们置于进入抗生素后时代的风险中。因此，全世界所有场所不动杆菌感染的发生率都在增加。不断变化的流行病学和不动杆菌感染的发病率使其成为一种日益重要的医学病原体。不用说，不动杆菌感染的治疗已经变得具有挑战性。改善结果将需要制定新的预防和/或治疗战略。不幸的是，要实现这些目标，需要填补重大的知识缺口。需要对候选疫苗进行识别和评估。鲍曼不动杆菌中的荚膜多糖几乎一无所知。表面多糖，如胶囊，已经形成了几种成功的针对细胞外病原体的疫苗，如b型流感嗜血杆菌、肺炎链球菌和某些血清型的脑膜炎奈瑟氏菌。这种方法可能也适用于不动杆菌。因此，这项提议的第一个目标，即确定鲍曼不动杆菌胶囊血清型的数量和相对流行率，将在目标1中实现。这些数据将为评估胶囊作为候选疫苗而设计的免疫和保护研究奠定基础，该研究将在目标2中完成。此外，在目标2中，将进行研究以确定最流行的3-5个胶囊血清型的结构。这些信息将被用来根据需要优化胶囊-蛋白质结合物的方法和设计，以优化免疫原性。这些数据还将被用来预测可能对人类表位的免疫反应。最后，结构数据将是评估包膜表位保守性的另一种手段。这项建议将产生新的重要数据，并填补开发新的预防方法以对抗鲍曼不动杆菌所需的知识空白。鲍曼不动杆菌是一种在平民、退伍军人和现役军人中日益重要的病原体。

DESCRIPTION (provided by applicant): Acientobacter baumannii is a gram-negative bacillus, which was initially known for causing health-care associated infections. Most recently the experience in Iraq/Kuwait/Afghanistan has reaffirmed the importance of A. baumannii in causing infections in wounded combatants. Further the prevalence of multi-drug and pan- resistant isolates of A. baumannii is increasing, placing us at risk for entering a post-antibiotic era. As a result, the incidence of Acinetobacter infection in all venues is increasing worldwide. The changing epidemiology and incidence of infections due to Acinetobacter establishes it as a pathogen of increasing medical importance. Needless to say, treatment of infections due to Acinetobacter has become challenging. Improved outcomes will require the development of new preventative and/or therapeutic strategies. Unfortunately, significant knowledge gaps exist that need to be filled to accomplish these goals. Vaccine candidates need to by identified and assessed. Virtually nothing is known about capsular polysaccharides in A. baumannii. Surface polysaccharides such as capsule have formed the basis for several successful vaccines directed against extracellular pathogens such as H. influenzae type b, S. pneumoniae, and certain serotypes of N. meningitidis. This approach may also be practical for Acinetobacter. Therefore, the first goal of this proposal, to determine the number and relative prevalence of A. baumannii capsule serotypes, will be accomplished in aim 1. These data will lay the foundation for immunization and protection studies designed to assess capsule as a vaccine candidate, which will be completed in aim 2. Also in aim 2 studies will be performed to determine the structures of 3-5 of the most prevalent capsular serotypes. This information will be used to optimize the method and design of capsule- protein conjugates as needed to optimize immunogenicity. These data will also be used to predict possible immune reactivity to human epitopes. Lastly, structural data will be an additional means to assess the conservation of capsular epitopes. This proposal will generate new and important data and fill knowledge gaps necessary for the development of new preventive approaches to combat A. baumannii, a pathogen of increasing medical importance in the civilian, veteran, and active military populations.