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）： 前杆菌鲍曼尼（Baumannii）是一种革兰氏阴性芽孢杆菌，最初以引起医疗保健相关感染而闻名。最近，在伊拉克/科威特/阿富汗的经验重申了鲍曼尼伊曲霉在引起受伤战斗人员感染的重要性。此外，鲍曼尼氏杆菌的多药和耐泛力分离株的患病率正在增加，使我们有进入抗生素后时代的风险。结果，在所有场所，所有场所感染的发生率都在全球增加。流行病学引起的流行病学和感染的发病率变化将其确立为增加医学重要性的病原体。不用说，由于杆菌引起的感染的治疗变得具有挑战性。改进的结果将需要制定新的预防和/或治疗策略。不幸的是，存在需要填补的重大知识差距来实现这些目标。候选疫苗需要通过确定和评估。几乎没有关于鲍曼尼曲霉中囊囊多糖的知识。诸如胶囊之类的表面多糖已成为针对细胞外病原体的几种成功疫苗的基础，例如B.型流感B，肺炎链球菌和某些脑膜炎N.这种方法对于射杆菌也可能是实用的。因此，该提案的第一个目标是在目标1中完成该提案的数量和相对患病率。这些数据将奠定免疫和保护研究的基础，旨在评估作为疫苗候选胶囊的囊囊，在AIM 2研究中还将在AIM 2中完成。还将在AIM 2中完成。该信息将用于优化胶囊蛋白结合物的方法和设计，以优化免疫原性。这些数据还将用于预测对人表位的免疫反应性。最后，结构数据将是评估囊膜表位保护的另一种手段。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A. Baumannii的知识空白，这是一种在平民，退伍军人和活跃的军事人群中提高医学重要性的病原体。 公共卫生相关性： 鲍曼尼（Baumannii）的杆菌是老兵，军事和平民人口中越来越重要的病原体。对许多人的抗菌素耐药性，在某些情况下，抗菌剂的抗菌剂使鲍曼尼曲霉的感染具有挑战性的治疗。目前，具有可预测活性的安全可靠药物目前不存在。开发有效的疫苗将有助于解决这一不断发展的临床问题。几乎没有关于鲍曼尼曲霉的囊多糖的知识，这些信息可能会导致新颖的预防或治疗方法。该提案的目的是开始填补这一主要知识差距，这可能具有重大的翻译含义。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构成新型预防或治疗措施的逻辑发展以改善鲍曼尼曲霉感染预后的基础。