Novel vaccine adjuvants to counter bioterrorist threats

描述(由申请人提供)：该项目的主要目标是开发以伽马菊粉为基础的佐剂作为安全有效的佐剂用于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批准，而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伽马菊粉的佐剂与病原体衍生的蛋白质或多肽相结合，开发至少一种针对A、B或C类病原体的疫苗。该项目的具体内容包括：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，从而创造出进一步开发利用类似免疫刺激途径的新型无毒佐剂的能力，验证菊粉佐剂与模式病原体衍生抗原(如Q热、志贺氏菌、黄病毒、小痘病毒、SARS)联合使用的生物活性，验证概念研究证明在经过验证的动物感染模型中的疫苗保护作用，以及临床前安全性和毒理学研究，使菊粉佐剂能够进入第一阶段人体试验。尽管纯重组抗原无疑比整体疫苗更安全，但一个主要问题是它们普遍缺乏免疫原性。这产生了对更有效但安全的佐剂的主要需求，这些佐剂与不可接受的毒性无关。因此，迫切需要一种耐受性好的有效佐剂，能够提高细胞免疫和体液免疫。菊粉佐剂提供了这样的优势，应该可以与生物恐怖主义疫苗很好地结合使用。

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.