Vaccine Development for Burkholderia amllei and B. pseudomallei

该提案针对B类病原体伯克霍尔德氏菌的疫苗开发 鼻疽假单胞菌和鼻疽伯克霍尔德菌。迫切需要和公认的需要更好地发展 通过使用疫苗和免疫刺激剂治疗类鼻疽和类鼻疽， 鼻疽我们认为在本项目中并行考虑这些病原体是适当的，因为它们是 在遗传水平上密切相关，并且有可能针对这些疾病的共同方法可以 被识别。该项目的目标是： (1)确定最佳的输送系统和蛋白质载体。 (2)开发优化的蛋白质-多糖结合方法。 (3)比较同源与异源蛋白质-多糖缀合物的功效。 (4)确定急性疾病模型中疫苗介导的保护作用的生物标志物和机制， 包括实验室小鼠、人源化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，能够保护免受这两种6。pseudomallei 和8.鼻疽感染这是一个重要的考虑因素，最终许可证和使用的潜力 适用于特殊人群，如幼儿、老年人、孕妇和 免疫功能低下的受试者。最终，本提案中概述的研究将建立一个数据集， 开始向食品和药物管理局成功提交研究性新药（IND）申请的流程， 药品监督管理总局.

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.