Expression of human lambda expands the repertoire of OmniChickens.

ABSTRACT: Most of the approved monoclonal antibodies used in the clinic were initially discovered in mice. However, many targets of therapeutic interest are highly conserved proteins that do not elicit a robust immune response in mice. There is a need for non-mammalian antibody discovery platforms which would allow researchers to access epitopes that are not recognized in mammalian hosts. Recently, we introduced the OmniChicken®, a transgenic animal carrying human VH3-23 and VK3-15 at its immunoglobulin loci. Here, we describe a new version of the OmniChicken which carries VH3-23 and either VL1-44 or VL3-19 at its heavy and light chain loci, respectively. The V?-expressing birds showed normal B and T populations in the periphery. A panel of monoclonal antibodies demonstrated comparable epitope coverage of a model antigen compared to both wild-type and V?-expressing OmniChickens. Kinetic analysis identified binders in the picomolar range. The V?-expressing bird increases the antibody diversity available in the OmniChicken platform, further enabling discovery of therapeutic leads.

SUBMITTER: Ching KH 

PROVIDER: S-EPMC6988971 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature