Development and evaluation of subunit vaccine CmeC against Campylobacter jejuni

空肠弯曲菌亚单位疫苗CmeC的研制及评价

• 批准号: 7186011
• 负责人: JUN LIN
• 金额: $ 16.63万
• 依托单位: UNIVERSITY OF TENNESSEE KNOXVILLE
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-20 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7186011
• 关键词: Acute; Address; Animal Model; Animals; Antibiotic Resistance; Antibiotics; Antibodies; Antigens; Bacteria; Bacterial Outer Membrane Proteins; Bile fluid; Campylobacter; Campylobacter infection; Campylobacter jejuni; Categories; Cessation of life; Chickens; Clinical; Condition; Developed Countries; Development; Drug resistance; Ensure; Evaluation; Foundations; Gastroenteritis; Genetic Polymorphism; Genome; Goals; Guillain-Barré Syndrome; Human; Immune; In Vitro; Infection; Intervention; Intestines; Lead; Macrolides; Mediating; Mediator of activation protein; Membrane Proteins; Modeling; Molecular; National Institute of Allergy and Infectious Disease; Operon; Organism; Outcome; Paralysed; Pathogenesis; Pharmacologic Substance; Positioning Attribute; Prevalence; Protein C; Public Health; Publishing; Pump; Regulation; Research; Research Personnel; Resistance; Respiratory Muscles; Reverse Transcriptase Polymerase Chain Reaction; Role; Solid; Subunit Vaccines; System; Testing; Time; United States; Vaccination; Vaccines; Work; antimicrobial; base; bile salts; clinical efficacy; design; efflux pump; enteritis; experience; foodborne; immunogenic; immunogenicity; improved; in vivo; innovation; novel; novel vaccines; pathogen; prevent; programs; protective effect; success; tool; vaccine development

DESCRIPTION (provided by applicant): Campylobacter jejuni, a NIAID Category B Priority Pathogen, is the leading bacterial cause of human enteritis in the United States and presents a major threat to public health. Increasing resistance of Campylobacter to clinical antibiotics in the past decade raised an urgent demand for the development of alternative intervention strategies, such as vaccination, to prevent and control Campylobacter infections. Despite recent progress on the elucidation of immunogenic and protective antigens in C. jejuni, vaccination of animals against C. jejuni colonization had only partial success and the immunogenic antigens with significant protective effect remain to be determined. The main goal of this R21 application is to develop and evaluate a novel subunit vaccine CmeC against C. jejuni. Outer membrane proteins (OMPs) of C. jejuni are considered the major mediators of the pathogen-host interaction, as a consequence, the promising candidates for the design of protective vaccines. Recently, we have characterized a unique OMP CmeC in Campylobacter. As a key component in multidrug efflux system CmeABC, CmeC contributes Campylobacter resistance to a broad spectrum of antimicrobials and is also essential for Campylobacter colonization in animal intestine by mediating bile resistance. As an immunogenic OMP in vivo, CmeC is widely distributed and constitutively expressed among various Campylobacter strains. Particularly, expression of CmeC is dramatically induced by bile salts present in intestine. Based on these observations, we hypothesize that CmeC is a novel subunit vaccine candidate for immune intervention against Campylobacter infections. To test our hypothesis, we plan to i) examine sequence polymorphism, antigenic homology, and in vitro immune protection of CmeC in primary Campylobacter isolates; ii) evaluate the immunogenicity and protective efficacy of a novel subunit CmeC vaccine in a chicken model of C. jejuni infection; and iii) determine the role of CmeC vaccine in potentiating the efficacy of clinical antibiotics. Once the proposed studies are completed, we expect to obtain critical information on the feasibility of targeting CmeC for immune protection against Campylobacter infections in humans. The unique dual functions of CmeC in intestinal colonization and antibiotic resistance greatly improve innovative aspect and significance of this application. Relevance: Campylobacter jejuni is the most prevalent foodborne bacterial pathogen causing human gastroenteritis in the U.S. The proposed research will provide novel information on the development of effective vaccine against C. jejuni to protect public health.

描述（由申请方提供）：空肠弯曲杆菌是NIAID B类优先病原体，是美国人类肠炎的主要细菌病因，对公共卫生构成重大威胁。在过去的十年中，弯曲杆菌对临床抗生素的耐药性不断增加，迫切需要开发替代干预策略，如疫苗接种，以预防和控制弯曲杆菌感染。尽管最近在阐明C. jejuni，接种动物抗C.空肠定殖仅部分成功，具有显著保护作用的免疫原性抗原仍有待确定。本R21申请的主要目标是开发和评估针对C的新型亚单位疫苗CmeC。空肠。外膜蛋白（OMPs）是C.空肠被认为是病原体-宿主相互作用的主要介质，因此，有希望用于设计保护性疫苗。最近，我们在弯曲杆菌中发现了一种独特的OMP CmeC。作为多药外排系统CmeABC中的关键组分，CmeC有助于弯曲杆菌对广谱抗菌剂的耐药性，并且通过介导胆汁耐药性对弯曲杆菌在动物肠道中的定植也是必不可少的。作为体内免疫原性OMP，CmeC在各种弯曲杆菌菌株中广泛分布并组成型表达。特别地，CmeC的表达被存在于肠中的胆汁盐显著诱导。基于这些观察结果，我们假设CmeC是一种新的亚单位疫苗候选人的免疫干预弯曲杆菌感染。为了验证我们的假设，我们计划i）检查原代弯曲杆菌分离株中CmeC的序列多态性、抗原同源性和体外免疫保护; ii）评估新型亚单位CmeC疫苗在鸡弯曲杆菌模型中的免疫原性和保护效力。空肠感染;和iii）确定CmeC疫苗在增强临床抗生素功效中的作用。一旦拟议的研究完成，我们希望获得关于靶向CmeC用于人类弯曲杆菌感染免疫保护的可行性的关键信息。CmeC在肠道定植和抗生素耐药性方面的独特双重功能大大提高了这种应用的创新性和意义。相关性：空肠弯曲菌是美国最常见的引起人类胃肠炎的食源性细菌病原体，该研究将为开发有效的空肠弯曲菌疫苗提供新的信息。空肠保护公众健康。