Proprietary phagemid vector

Rabbit antibodies possess higher CDR sequence and length diversity in both light and heavy chains compared to mouse or human antibodies; rabbit antibodies often possess pM K_D binding affinity compared to nM K_D for mouse antibodies. This makes rabbit monoclonal antibodies excellent sources of diagnostic or therapeutic lead candidates. However, rabbit Fabs have a unique disulfide architecture that prevents their expression in E. coli. Historically, this has led to the development of sub-optimal systems that do not use the full rabbit immune repertoire, including the use of a rabbit strain that lacks the dominant disulfide-containing K1 isotype, construction of chimeric Fabs containing human constant domains, or significant engineering in scFv format. All these workarounds necessarily limit the diversity of the resulting immune library and fail to access the full power of the rabbit immune repertoire. We have had many discussions with clients and industry peers who have given up on constructing immune phage display libraries from rabbits due to their inability to express rabbit antibody fragments in E. coli

Indeed, our early attempts with rabbit Fab-phage selection at Abwiz Bio using an industry standard phagemid vector resulted in few binders and low sequence diversity from an immune library (left image below). However, determined to unlock rabbit Fab display, we put significant effort into optimizing our vector by incorporating unique elements. When using our proprietary vector with the same immune library, we were able to reliably isolate hundreds of binders with diverse sequences (right image below), including a majority of clones possessing the dominant kappa K1 isotype.