Acellular vaccines against Francisella tularensis

描述(申请人提供)：兼性胞内细菌 图拉氏方济氏菌可引起严重肺炎和死亡。 在吸入极少量的感染性颗粒之后。为 因此，图拉氏丝虫被认为是一种主要的生物战剂。 对这种病原体的获得性宿主免疫主要是T细胞介导的 而不是幽默。图拉氏丝虫的减毒株是一种有效的活体 针对病原体强毒株的疫苗。然而，这种菌株保留了 它对小鼠的毒性，如果给药可能会导致疾病 免疫功能受损的个体。因此，为了大规模接种疫苗，定义了一种 快速有效的无细胞疫苗将比目前的活疫苗更可取。 我们研究所开发了一种新的疫苗递送技术，基于 由各种考古细菌的总极性脂类制成的脂质体。 这些脂质体被称为古生物小体，能产生强大的细胞免疫。 对被困在其中的模型抗原的反应，而不需要任何 额外的免疫兴奋剂。最近，我们发现了一种短肽抗原 另一种胞内致病菌，单核细胞增生性李斯特氏菌，包装在 古生物提供了一种高水平的保护性免疫力 只接种一次疫苗的小鼠李斯特氏菌病模型中的病原体。因为 多项研究表明，对抗F。 图拉氏菌和单核细胞增多性李斯特氏菌的适当抗原很可能是 包裹在古生物体内的前病原体将提供有效的脱细胞 疫苗。这项提案将探索这一可能性。预计将会有 拟议研究的结果将适用于 针对其他细胞内呼吸道病原体的无细胞疫苗，如 结核分枝杆菌和肺炎衣原体。

DESCRIPTION (Provided by Applicant): The facultative intracellular bacterial pathogen, Francisella tularensis, can cause severe pneumonia and death following the inhalation of very small numbers of infectious particles. For this reason, F. tularensis is considered a primary biological warfare agent. Acquired host immunity against this pathogen is predominantly T-cell-mediated rather than humoral. An attenuated strain of F. tularensis is an effective live vaccine against virulent strains of the pathogen. However, this strain retains its virulence for mice, and might cause disease if administered to immunocompromised individuals. Thus, for mass-vaccination purposes, a defined fast-acting acellular vaccine would be preferable to the current live vaccine. Our institute has developed a novel vaccine delivery technology based on liposomes manufactured from the total polar lipids of various Archaebacteria. These liposomes termed, archaeosomes, generate robust cell-mediated immune responses to model antigens entrapped within them, without the aid of any additional immune stimulants. Recently, we showed that a short peptide antigen of another intracellular pathogen, Listeria monocytogenes, packaged in archaeosomes, provides a high level of protective immunity against this pathogen in a murine listeriosis model after only a single vaccination. Because multiple studies indicate that the same host defenses are needed to combat F. tularensis and L. monocytogenes, it is likely that appropriate antigens of the former pathogen encapsulated in archaeosomes will provide effective acellular vaccines. This proposal will explore this possibility. It is expected that the findings from the proposed studies will be applicable to the development of acellular vaccines against other intracellular respiratory pathogens such as Mycobacterium tuberculosis, and Chlamydia pneumoniae.