Rapid Quality Control Technology for Biodefense Vaccines

描述（由申请方提供）：由于预期在不久的将来CDC A类病原体的潜在疫苗数量会显著增加，因此必须开发和验证快速反应质量控制技术。该提案的主要目标是开发和验证适用于肽、蛋白质和颗粒等疫苗的这种技术。所提出的技术具有几个明显的优势，使其特别适合在分布式环境中的快速响应。其独特的属性包括执行速度、对重要结构变化的敏感性、低成本和固有的自动化功能。目前生物制品（包括疫苗）的质量控制技术缓慢、复杂，并且经常需要进行体内研究以评估产品的生物活性水平。与活动直接相关的结构信息非常有用，但很难获得。所提出的技术集中于结构的签名或指纹的开发。相对于从已知结构和/或活性性质的参考样品获得的其它特征来定义特征。开发和利用特征所涉及的技术将物理化学分析与数学技术相结合。签名随后以易于解释的方式呈现，无论是数字还是视觉。拟议研究的第一阶段将侧重于可行性研究，为各种血清型的C。肉毒杆菌毒素及其片段。将开发对生产和制剂方面敏感的特征，从而产生不同水平的生物活性。将检查各种辅料、pH值、盐和冻干的影响等问题。I期研究的主要目的是证明构建与各种治疗和条件的影响相关的结构特征的能力，并证明其提供可用于快速质量控制检测的独特信息的可行性。拟议研究的第二阶段将集中于为几种A类疫苗开发额外的特征，进一步分析验证问题，以及开发自动化实验台和便携式生物芯片平台，以快速可靠的方式获得特征。

DESCRIPTION (Provided by applicant): Due to the anticipated significant increase in the number of potential vaccines for CDC Category A agents in the near future, it is imperative that a rapid response quality control technology be developed and validated. The key objective of this proposal is to develop and validate such a technology applicable to vaccines such as peptides, proteins and particles. The proposed technology has several distinct advantages making it particularly suitable for rapid response in distributed environments. Among its unique attributes are speed of execution, sensitivity to structural changes of importance, low cost, and inherent automation capabilities. Present quality control techniques for biologicals, including vaccines, are slow, complex, and frequently require in vivo studies to assess the level of biological activity of the product. Structural information that is directly related to activity is highly useful, but very difficult to obtain. The proposed technology focuses on development of a signature, or a fingerprint, of the structure. The signature is defined in relation to other signatures, obtained from reference samples of known structural and/or activity properties. The technology involved in the development and utilization of signatures combines physico-chemical assays with mathematical techniques. The signature is subsequently presented in an easy to interpret manner, either numerically or visually. Phase I of the proposed study would focus on a feasibility study developing signatures for various serotypes of C. botulinum toxins, as well as their fragments. Signatures will be developed that are sensitive to production and formulation aspects which result in varying levels of bioactivity. Issues such as the effects of various excipients, pH, salts, and lyophilization would be examined. The principal aim of Phase I study would be to demonstrate the ability to construct structural signatures that correlate with the effects of various treatments and conditions, and to prove its feasibility to provide unique information that could be used during rapid quality control testing. Phase II of the proposed study would concentrate on development of additional signatures for several Category A vaccines, on further analytical validation issues, and on development of automated lab-bench and portable biochip platforms to obtain the signatures in a rapid and reliable manner.