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: 8142286
• 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/8142286
• 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; 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，最初被认为是引起医疗保健相关感染的细菌。最近在伊拉克/科威特/阿富汗的经验再次证实了A.鲍曼不动杆菌在受伤的战斗人员中引起感染。此外，多重耐药和泛耐药的A.鲍曼不动杆菌正在增加，使我们面临进入后抗生素时代的风险。因此，在世界范围内，所有场馆中不动杆菌感染的发生率都在增加。由于不动杆菌感染的流行病学和发病率的变化，使其成为医学重要性日益增加的病原体。毋庸置疑，不动杆菌属感染的治疗已变得具有挑战性。改善结果将需要开发新的预防和/或治疗策略。不幸的是，要实现这些目标，还存在着重大的知识差距。候选疫苗需要被识别和评估。事实上，对A.鲍曼不动杆菌。表面多糖如荚膜已经形成了几种成功的针对细胞外病原体如H.流感B型、S. pneumoniae和某些血清型的N.脑膜炎这种方法对于不动杆菌也是实用的。因此，本建议的第一个目标，是确定A.将在目标1中完成鲍曼不动杆菌胶囊血清型。这些数据将为旨在评估胶囊作为候选疫苗的免疫和保护研究奠定基础，该研究将在目标2中完成。同样在目标2中，将进行研究以确定3-5种最流行的荚膜血清型的结构。该信息将用于根据需要优化胶囊-蛋白缀合物的方法和设计，以优化免疫原性。这些数据也将用于预测对人表位的可能免疫反应性。最后，结构数据将是评估荚膜表位保守性的额外手段。这项建议将产生新的重要数据，填补知识空白，为制定新的预防方法来防治A。鲍曼不动杆菌，一种在平民、退伍军人和现役军人群体中医学重要性日益增加的病原体。 公共卫生相关性： 鲍氏不动杆菌是退伍军人、军人和平民人群中日益重要的病原体。对许多抗菌药物的耐药性，在某些情况下对所有抗菌药物的耐药性使得A.鲍曼不动杆菌感染具有挑战性。安全可靠的药剂，对A具有可预测的活性。鲍曼不动杆菌目前已不存在。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，对A.鲍曼不动杆菌，这一信息可能导致新的预防或治疗方法。本提案的目标是开始填补这一重大的知识空白，这可能具有重大的翻译影响。将进行研究，以确定胶囊作为疫苗抗原的潜力。从这一建议产生的数据有可能形成新的预防或治疗措施的逻辑发展的基础，以改善在A。鲍曼不动杆菌感染。