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.

While neutralizing efficiency is dependent on many different antibody-binding characteristics (e.g. epitope recognition, fine specificity, reaction rate kinetics), there is some evidence that the affinity of the antibody correlates well with its neutralization ability (Burton, 2002; Hudson and Souraiu, 2003; Nelson et al., 2007) . With this in mind, the CDR regions of 4049Fab14 were subjected to affinity maturation by a strategy called GSSM TM . This method produces every possible amino acid at each site individually within the protein or region of interest. There are 27 and 40 amino acids in the three CDR regions of the light and heavy chains of 4049Fab14, respectively. As this screen was performed simultaneously with the HuFR TM screen, each of these amino acids was individually mutated to all other possible codons in the backbone of the mouse -human chimera.