Novel vaccine adjuvants to counter bioterrorist threats

描述（由申请人提供）：本项目的主要目标是开发基于γ菊粉的佐剂作为安全有效的佐剂，用于针对A、B和C类生物恐怖主义病原体的疫苗。由于佐剂本身不能获得监管部门的批准，只能作为疫苗组合物的一部分，因此进一步的目标是通过将基于γ菊粉的佐剂与病原体衍生的蛋白质或肽结合，开发至少一种针对a、B或C类病原体的疫苗。该项目的具体组成部分包括用于生物恐怖主义亚单位疫苗的菊粉佐剂的物理化学表征和优化，确定菊粉佐剂的作用机制，从而创造开发利用类似免疫刺激途径的新型无毒佐剂的能力，验证菊粉佐剂与模型病原体衍生抗原(例如Q热，志贺氏菌，黄病毒，天花，SARS)，证明疫苗在经过验证的动物感染模型中具有保护作用的概念证明研究，以及临床前安全性和毒理学研究，使基于菊粉的佐剂能够进入1期人体试验。虽然纯重组抗原无疑比整个生物体疫苗更安全，但一个主要问题是它们普遍缺乏免疫原性。这就产生了对更有效、更安全、没有不可接受毒性的佐剂的主要需求。因此，迫切需要一种耐受性良好且有效的佐剂，能够增强细胞和体液免疫。以菊粉为基础的佐剂就具有这样的优势，与生物恐怖主义疫苗结合使用应该能很好地发挥作用。

DESCRIPTION (provided by applicant): This Project's primary goal is to develop the use of gamma inulin-based adjuvants as safe and effective adjuvants for use in vaccines against Category A, B and C bioterrorism pathogens. As adjuvants cannot receive regulatory approval in their own right but only as part of a vaccine composition, a further objective is to develop at least one vaccine against a Category A, B or C pathogen by combining gamma inulin-based adjuvant with pathogen derived proteins or peptides. Specific components of the project include the physico-chemical characterization, and optimization of inulin-based adjuvants for use in bioterrorism subunit vaccines, determination of the mechanisms of action of inulin-based adjuvants, thereby creating the ability to develop further novel nontoxic adjuvants that utilize similar immuno-stimulatory pathways, validation of the biological activity of inulin-based adjuvants in combination with model pathogen-derived antigens (e.g. Q Fever, Shigella, flaviviruses, small pox, SARS), proof of concept studies demonstrating vaccine protection in validated animal infection models and pre-clinical safety and toxicology studies to enable inulin-based adjuvants to advance into phase 1 human trials. Although pure recombinant antigens although undoubtedly safer than whole organism vaccines, a major problem is their general lack of immunogenicity. This has created a major demand for more potent yet safe adjuvants not associated with unacceptable toxicity. Hence the urgent need for a well tolerated and effective adjuvant capable of boosting both cellular and humoral immunity. Inulin-based adjuvants offer just such advantages and should work well in combination with bioterrorism vaccines.