Acellular vaccines against Francisella tularensis

描述（由申请人提供）：兼性胞内细菌 病原体，土拉热弗朗西丝菌，可导致严重的肺炎和死亡 吸入极少量的传染性颗粒后。为 这个原因，F。土拉热被认为是一种主要的生物战剂。 针对该病原体的获得性宿主免疫主要是T细胞介导的 而不是体液。用F.土拉热菌是一种有效活菌 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， 免疫力低下的人。因此，为了大规模接种疫苗， 快速作用的无细胞疫苗比目前的活疫苗更可取。 我们的研究所开发了一种新的疫苗输送技术， 由各种古细菌的总极性脂质制成的脂质体。 这些脂质体被称为古细菌体， 在没有任何辅助的情况下， 额外的免疫刺激剂。最近，我们发现一种短肽抗原 另一种细胞内病原体单核细胞增生李斯特菌， 古细菌体，提供了高水平的保护性免疫力， 病原体在鼠绦虫病模型中的作用。因为 多项研究表明，需要相同的宿主防御来对抗F。 tularensis和L.单核细胞增多症，很可能是适当的抗原， 包封在古细菌体中的前病原体将提供有效的非细胞 疫苗。本提案将探讨这种可能性。预计该 拟议研究的结果将适用于发展 针对其他细胞内呼吸道病原体的无细胞疫苗， 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.