Francisella tularensis purine auxotrophs as vaccines candidates

土拉弗朗西斯菌嘌呤营养缺陷型作为候选疫苗

• 批准号: 7700368
• 负责人: THOMAS C. ZAHRT
• 金额: $ 15.96万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-03-01 至 2009-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7700368
• 关键词: Acute; Address; Attenuated; Attenuated Live Virus Vaccine; Attenuated Vaccines; Bacteria; Biological Assay; Biological Models; Biological Warfare; Categories; Characteristics; Deletion Mutation; Disease; Dose; Event; Facility Construction Funding Category; Francisella tularensis; Fright; Funding; Genes; Goals; Growth; Human; Immunity; In Vitro; Infection; Libraries; Licensing; Mus; Organism; Purines; Rate; Research Proposals; Route; Technology; Time; Tularemia; United States Food and Drug Administration; United States National Institutes of Health; Vaccines; Virulence; Virulent; auxotrophy; base; concept; immunogenic; improved; in vivo; insight; macrophage; mortality; mouse model; mutant; novel vaccines; pathogen; promoter; purine; research study; therapeutic target; vector

Francisella tularensis is a facultative intracellular zoonotic pathogen and the etiological agent of tularemia. It has an infectious dose of between 1-10 organisms, and is capable of causing an acute debilitating disease in humans with high mortality rates. F. tularensis has been designated a Category A Select Agent as it is a potential agent of biowarfare. Little is currently known about the virulence determinants utilized by this organism to cause disease in the host. In addition, there is no licensed vaccine available in the event of an intentional release of this bacterium. Identification of genes contributing to virulence of F. tularensis within the host would greatly improve our understanding of the mechanisms utilized by this organism to cause disease, and facilitate the construction of novel vaccine strains capable of providing protective immunity. In this New Opportunities application, an unmarked purMCD deletion mutant will be generated in a type A strain of F. tularensis and analyzed for its ability to serve as a live attenuated vaccine candidate and host strain for in vivo expression technology (IVET)-based virulence gene identification. Collectively, these studies are expected to provide important insights into the genes required by F. tularensis for growth within the host. Importantly, experiments proposed in this application will provide advanced proof-of-concept of purine auxotrophs as viable live vaccine candidates for F. tularensis.

土拉菌是兼性胞内人畜共患病原体，是土拉菌病的病原。它