Rapid discovery and optimization of therapeutic antibodies against emerging infectious diseases

Rogers, J.; Schoepp, R.J.; Schröder, O.; Clements, T.L.; Holland, T.F.; Li, J.Q.; Li, J.; Lewis, L.M.; Dirmeier, R.P.; Frey, G.J.; Tan, X.; Wong, K.; Woodnutt, G.; Keller, M.; Reed, D.S.; Kimmel, B.E.; Tozer, E.C.

Production of effective antibodies has been the subject of extensive research and with significant success, i.e. 20 recombinant antibodies approved as therapeutics by the FDA as of 2006 (www.researchandmarkets.com/reports/354677). Many organizations involved in this work either focus on the discovery of novel antibodies and subsequently, outsource necessary optimization efforts or vice versa. In contrast, we utilized technology that comprehensively encompasses both the discovery and optimization components of producing therapeutic antibodies. In addition to eliminating potential coordination issues between organizations, this centralized effort can reduce timelines. Using SARS-CoV as the model system, we have discovered, humanized, and optimized the functional performance of novel neutralizing antibodies that inhibit SARS infection in permissive cells and viral replication in vivo. These discovery and evolution strategies will potentially be useful in reducing the current susceptibility to biological threats.