Systematic Antibody Optimization

Optimization of antibody affinity and specificity is of paramount importance to the military for the development of biological warfare agent receptors and vaccine components. Exhaustive saturation mutagenesis of the complete antigen binding site for such optimization must typically involve the construction and characterization of several hundred mutants. Using conventional mutagenesis, the expense and time needed to complete such an undertaking are daunting. Systems & Processes Engineering Corporation (SPEC) and Drs. Brent L. Iverson and George Georgiou propose to demonstrate a novel method for systematic optimization of antibodies. Drs. Iverson and Georgiou have developed a new method for systematic in-vitro saturation mutagenesis which provides for a highly efficient method to screen and mutate antibodies and characterize the mutants. SPEC proposes to demonstrate this novel approach with a botulinum toxin (BoTX) antibody. SPEC will also develop a design for scale-up and automation of this novel process to provide a rapid-response, low-cost system for the systematic optimization of antibodies. The design will be implemented in a Phase II prototype. This system could be used to optimize antibodies for other military significant agents including plague, anthrax, straphylococcal enterotoxin B, Venezuelan equine encephalitis virus (VEE), and dengue virus to name a few. A cost effective, rapid response in vitro saturation mutagenesis system has broad application. Development of high-specificity, high-affinity antibodies where none currently exist will be possible. Systematic optimization of antibodies can provide optimized receptors for detection and monitoring of chemical and biological agents, water monitoring, agricultural product inspection, illicit drug detection, and biomedical instrumentation. The scale-up manufacturing system will allow fast, low-cost optimization of antibodies for biosensor applications clinical immunoassays. and new pathogenic treatment protocols and drugs.