Analysis of A Baumannii Capsule as a Vaccine Candidate

鲍曼氏菌胶囊作为候选疫苗的分析

• 批准号: 8255320
• 负责人: THOMAS A RUSSO
• 金额: --
• 依托单位: VA WESTERN NEW YORK HEALTHCARE SYSTEM
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-04-01 至 2015-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8255320
• 关键词: Acinetobacter; Acinetobacter Infections; Acinetobacter baumannii; Afghanistan; Antibiotics; Antimicrobial Resistance; Bacillus (bacterium); Blood Vessels; CD59 Antigen; Child; Clinical; Community-Acquired Infections; Data; Development; Devices; Epidemiology; Epitopes; Evolution; Foundations; Goals; Haemophilus influenzae; Healthcare; Human; Immune; Immunization; Incidence; Infection; Iraq; Knowledge; Kuwait; Lead; Libraries; Location; Long-Term Care; Measures; Medical; Methods; Military Personnel; Monoclonal Antibodies; Multi-Drug Resistance; Neuraxis; Operative Surgical Procedures; Outcome; Patients; Pharmaceutical Preparations; Pharmacologic Substance; Polysaccharides; Population; Prevalence; Preventive; Proteins; Relative (related person); Reporting; Research Design; Resistance; Respiratory System; Respiratory tract structure; Risk; Role; Serotyping; Services; Site; Streptococcus pneumoniae; Structure; Surface; Therapeutic; Urinary tract; Vaccine Antigen; Vaccines; Veterans; Work; antimicrobial; antimicrobial drug; base; capsule; combat; design; experience; extracellular; immunogenicity; improved; member; neurosurgery; novel; pathogen; posters; public health relevance; vaccine candidate

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. PUBLIC HEALTH RELEVANCE: Acinetobacter baumannii is an increasingly important pathogen in the veteran, military and civilian populations. Antimicrobial resistance to many, and in some cases all, antimicrobial agents has made treatment of A. baumannii infections challenging. Safe reliable agents with predictable activity against A. baumannii are presently non-existent. Development of an efficacious vaccine would assist in solving this evolving clinical problem. Virtually nothing is known about the capsular polysaccharides of A. baumannii and this information may lead to novel preventative or therapeutic approaches. The goal of this proposal is to begin to fill this major knowledge gap, which may have has significant translational implications. Studies will be performed that will determine the potential of capsule as a vaccine antigen. Data generated from this proposal have the potential to form the basis for the logical development of novel preventative or perhaps therapeutic measures to improve outcome in A. baumannii infections.

描述（由申请人提供）： 鲍曼不动杆菌是一种革兰氏阴性杆菌，最初因引起医疗保健相关感染而闻名。最近，伊拉克/科威特/阿富汗的经验再次证实了鲍曼不动杆菌在导致受伤战斗人员感染方面的重要性。此外，鲍曼不动杆菌的多药和泛耐药菌株的流行正在增加，使我们面临进入后抗生素时代的风险。因此，全球范围内所有场所的不动杆菌感染发病率都在增加。不动杆菌引起的流行病学和感染发生率的变化使其成为一种具有日益增加的医学重要性的病原体。不用说，治疗不动杆菌引起的感染已变得具有挑战性。改善结果需要制定新的预防和/或治疗策略。不幸的是，为了实现这些目标，需要填补巨大的知识空白。候选疫苗需要经过识别和评估。事实上，我们对鲍曼不动杆菌中的荚膜多糖一无所知。表面多糖（例如胶囊）已成为针对细胞外病原体（例如 b 型流感嗜血杆菌、肺炎链球菌和脑膜炎奈瑟氏球菌的某些血清型）的几种成功疫苗的基础。这种方法对于不动杆菌也可能是实用的。因此，本提案的第一个目标，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。这些数据将为旨在评估鲍曼不动杆菌胶囊血清型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，还将进行研究以确定 3-5 种最流行的荚膜血清型的结构。该信息将用于优化胶囊蛋白缀合物的方法和设计，以优化免疫原性。这些数据还将用于预测对人类表位可能的免疫反应。最后，结构数据将成为评估荚膜表位保守性的另一种手段。该提案将产生新的重要数据，并填补开发新的预防方法来对抗鲍曼不动杆菌所需的知识空白，鲍曼不动杆菌是一种对平民、退伍军人和现役军人具有日益重要的医疗重要性的病原体。 公共卫生相关性： 鲍曼不动杆菌是退伍军人、军人和平民中日益重要的病原体。对许多（在某些情况下）所有抗菌药物的耐药性使得鲍曼不动杆菌感染的治疗具有挑战性。目前还不存在针对鲍曼不动杆菌具有可预测活性的安全可靠的药物。开发有效的疫苗将有助于解决这一不断发展的临床问题。事实上，我们对鲍曼不动杆菌的荚膜多糖一无所知，这些信息可能会导致新的预防或治疗方法。该提案的目标是开始填补这一重大知识空白，这可能具有重大的转化意义。将进行研究以确定胶囊作为疫苗抗原的潜力。该提案产生的数据有可能成为逻辑开发新的预防或治疗措施的基础，以改善鲍曼不动杆菌感染的结果。