(242b) A Comparison of Antibodies Isolated from Immune Libraries by Two Different Anchored Periplasmic Expression (APEx) Systems

High affinity antibodies to the Protective Antigen (PA) component of the Bacillus anthracis toxin are in late stage testing for prophylaxis and therapy against anthrax intoxication. However, recent studies (Nowakowski, A et al.) indicate that treatment with multiple antibodies simultaneously can confer a synergistic protection to toxin challenge. To explore multi-antibody therapeutic approaches, antibodies toward the protective antigen (PA) component of the B. anthracis exotoxin were isolated from immune libraries using two variations of the E. coli based protein library screening technology, Anchored Periplasmic Expression (APEx) (Harvey, B.R. et al., Mazor, Y. et al.). Full length antibodies and scFv antibodies with nanomolar affinities were isolated as early as the second round of flow cytometric screening. While all of the scFvs were easily converted to functional full-length antibodies, the converse was not true. These results indicate the E¬-clonal system is better suited than the original APEx system for the isolation of a diverse array of antibodies with a wide affinity range. Furthermore, all antibodies isolated are currently being evaluated for multi-antibody therapy.

Nowakowski, A. et al. (2002) Proceedings of the National Academy of Sciences of USA 99(17): 11346

Harvey, B.R. et al. (2004) Proceedings of the National Academy of Sciences of USA 101(25): 9193

Mazor, Y, et al. (2007) Nature Biotechnology 25(5): 563