PDF(Pubmed)
Abstract：
Tularemia is a zoonotic disease caused by the facultative intracellular gram-negative bacterium Francisella tularensis. F. tularensis has a very low infection dose by the aerosol route which can result in an acute, and potentially lethal, infection in humans. Consequently, it is classified as a Category A bioterrorism agent by the US Centers for Disease Control (CDC) and is a pathogen of concern for the International Biodefence community. There are currently no licenced tularemia vaccines. In this study we report on the continued assessment of a tularemia subunit vaccine utilising β-glucan particles (GPs) as a vaccine delivery platform for immunogenic F. tularensis antigens. Using a Fischer 344 rat infection model, we demonstrate that a GP based vaccine comprising the F. tularensis lipopolysaccharide antigen together with the protein antigen FTT0814 provided partial protection of F344 rats against an aerosol challenge with a high virulence strain of F. tularensis, SCHU S4. Inclusion of imiquimod as an adjuvant failed to enhance protective efficacy. Moreover, the level of protection afforded was dependant on the challenge dose. Immunological characterisation of this vaccine demonstrated that it induced strong antibody immunoglobulin responses to both polysaccharide and protein antigens. Furthermore, we demonstrate that the FTT0814 component of the GP vaccine primed CD4+ and CD8+ T-cells from immunised F344 rats to express interferon-γ, and CD4+ cells to express interleukin-17, in an antigen specific manner. These data demonstrate the development potential of this tularemia subunit vaccine and builds on a body of work highlighting GPs as a promising vaccine platform for difficult to treat pathogens including those of concern to the bio-defence community.
摘要：
Tularemia是由兼性细胞内革兰氏阴性细菌Francisellatularensis引起的人畜共患疾病。F.Tularensis通过气雾剂途径具有非常低的感染剂量，可导致急性，并且可能致命，人类感染。因此,它被美国疾病控制中心（CDC）列为A类生物恐怖主义病原体，是国际生物防御界关注的病原体。目前没有许可的tularemia疫苗。在这项研究中，我们报告了利用β-葡聚糖颗粒（GPs）作为免疫原性土拉氏杆菌抗原的疫苗递送平台的土拉氏杆菌亚单位疫苗的持续评估。使用Fischer344大鼠感染模型，我们证明了一种基于GP的疫苗，该疫苗包含土拉沙氏杆菌脂多糖抗原和蛋白质抗原FTT0814，为F344大鼠提供了部分保护，使其免受高毒力土拉沙氏杆菌的气溶胶攻击。SCHUS4。包含咪喹莫特作为佐剂不能增强保护功效。此外，所提供的保护水平取决于攻击剂量.该疫苗的免疫学表征表明，它诱导了对多糖和蛋白质抗原的强抗体免疫球蛋白应答。此外，我们证明GP疫苗的FTT0814成分可使免疫F344大鼠的CD4+和CD8+T细胞表达干扰素-γ，和CD4+细胞以抗原特异性方式表达白细胞介素-17。这些数据证明了这种tularemia亚单位疫苗的发展潜力，并建立在一系列工作基础上，突出了GP作为一种有前途的疫苗平台，用于难以治疗病原体，包括生物防御界关注的病原体。
