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.

弗朗西斯菌（Francisella toarlensis）是一种辅助细胞内人畜共患病原体，是t骨的病因。它 具有1-10个生物之间的传染性剂量，能够引起急性使人衰弱的疾病 死亡率高的人。 F. Tularensis已被指定为一个类别的选择代理，因为它是 Biowarfare的潜在代理。目前对此使用的毒力决定因素知之甚少 生物体在宿主中引起疾病​​。此外，在发生的情况下，没有许可疫苗 故意释放该细菌。鉴定有助于f。tularensis毒力的基因 宿主将大大提高我们对这种生物使用机制的理解 疾病，并促进能够提供保护性免疫的新型疫苗菌株的结构。在 这种新的机会应用程序，将在A型中生成一个未标记的purmcd删除突变体 F. tularensis的菌株，并分析了其充当活疫苗候选和宿主的能力 体内表达技术（IVET）基于毒力基因鉴定的菌株。总的来说，这些 预计研究将为F. tularensis所需的基因提供重要的见解 主人。重要的是，本应用程序中提出的实验将为您提供高级概念证明 嘌呤的合子作为f。tularensis的可行的活疫苗候选物。