Vaccine Development for Burkholderia amllei and B. pseudomallei

这项建议是针对B类毒剂伯克霍尔德氏菌的疫苗的开发 Passomalli和Burkholderia Mallei。人们迫切需要更好地发展，这是公认的 通过使用疫苗和免疫刺激剂预防类鼻疽和 红毛虫。我们认为在这个项目中同时考虑这些病原体是合适的，因为它们是 在基因水平上密切相关，而且有可能对这些疾病的共同方法可以 被指认出来。该项目的目标是： (1)确定最佳的输送系统和蛋白质载体。 (2)建立优化的蛋白质-多糖偶联方法。 (3)比较同源和异种蛋白质-多糖偶联物的疗效。 (4)在急性疾病模型中确定疫苗介导保护的生物标志物和机制， 包括实验室小鼠、人源化的SCID小鼠和非人灵长类动物模型。 我们的主要目标是设计一种非活疫苗，能够预防这两种假鼻疽。 8.锤状病毒感染。这是最终获得许可和潜在使用的一个重要考虑因素 适用于特殊人群，如幼儿、老年人、孕妇和 免疫功能受损的受试者。最终，本提案中概述的研究将建立一个数据集，以 开始向食品和药物管理局成功提交调查性新药(IND)申请的过程 药品管理局。

This proposal is directed towards the development of vaccines for the category B agents Burkholderia pseudomallei and Burkholderia mallei. There is an urgent and acknowledged need to develop better Drophylactic countermeasures through the use of vaccines and immune stimulants for both melioidosis and glanders. We believe it is appropriate to consider these pathogens in parallel in this project because they are closely related at a genetic level, and there is a possibility that common approaches to these diseases can be identified. The aims of this project are to: (1) Identify optimal delivery systems and protein carriers. (2) Develop optimized protein-polysaccharide conjugation methods. (3) Compare efficacy of homologous versus heterologous protein-polysaccharide conjugates. (4) Identify biomarkers and mechanisms of vaccine-mediated protection in acute disease models, including the laboratory mouse, the humanized SCID mouse, and nonhuman primate models. Our principal aim is to devise a non-living vaccine which is able to protect against both 6. pseudomallei and 8. mallei infection. This is an important consideration for eventual licensure and use with potential applications for special populations such as young children, the elderly, pregnant women and immunocompromised subjects. Ultimately, the studies outlined in this proposal will establish a data set to begin the process of a successful submission of an investigative new drug (IND) application to the Food and Drug Administration.