Rapid Quality Control Technology for Biodefense Vaccines

生物防御疫苗的快速质量控制技术

• 批准号: 6555373
• 负责人: BORIS Y ZASLAVSKY
• 金额: $ 9.92万
• 依托单位: ANALIZA, INC.
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-08-15 至 2003-08-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6555373
• 关键词: bioassay; bioterrorism /chemical warfare; botulinum toxins; chemical fingerprinting; chemical structure; drug quality /standard; mathematics; portable biomedical equipment; protein structure; technology /technique development; vaccine development

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.

描述(由申请人提供)：由于预计在不久的将来疾控中心A类药物的潜在疫苗数量将显著增加，开发和验证快速反应质量控制技术是当务之急。这项提议的关键目标是开发和验证适用于多肽、蛋白质和颗粒等疫苗的这种技术。提出的技术具有几个明显的优点，使其特别适合于分布式环境中的快速响应。它的独特属性包括执行速度、对重要结构变化的敏感度、低成本和固有的自动化能力。目前生物制品，包括疫苗的质量控制技术缓慢、复杂，而且经常需要体内研究来评估产品的生物活性水平。与活动直接相关的结构性信息非常有用，但很难获得。这项拟议的技术专注于开发该结构的签名或指纹。根据从已知结构和/或活性性质的参考样本获得的其他签名来定义该签名。开发和利用签名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，无论是数字形式还是视觉形式。拟议研究的第一阶段将侧重于开发各种血清型肉毒杆菌毒素及其片段的特征的可行性研究。将开发对生产和配方方面敏感的签名，这些方面会导致不同程度的生物活性。诸如各种赋形剂、pH、盐类和冷冻干燥的影响等问题将被研究。第一阶段研究的主要目的将是证明构建与各种处理和条件的影响相关的结构特征的能力，并证明其提供可在快速质量控制测试期间使用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类疫苗开发更多的签名，进一步的分析验证问题，以及开发自动化实验室平台和便携式生物芯片平台，以快速和可靠的方式获得签名。