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.
