Expression of human lambda expands the repertoire of OmniChickens

• Published in: PloS one Vol. 15; no. 1; p. e0228164
• Main Authors: Ching, Kathryn H, Berg, Kimberley, Morales, Jacqueline, Pedersen, Darlene, Harriman, William D, Abdiche, Yasmina N, Leighton, Philip A
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 29.01.2020; Public Library of Science (PLoS)
• Subjects: Analysis; Animal genetic engineering; Animals; Animals, Genetically Modified - genetics; Animals, Genetically Modified - immunology; Antibodies; Antibodies, Monoclonal - genetics; Antibodies, Monoclonal - immunology; Antigenic determinants; Antigens; B cells; B-Lymphocytes - immunology; Binders; Biology and Life Sciences; Birds; Book publishing; Chickens - genetics; Chickens - immunology; Epitopes; Genes; Genetic engineering; Genetically modified animals; Health aspects; Humans; Immune response; Immune system; Immunity, Humoral; Immunoglobulin Heavy Chains - genetics; Immunoglobulin lambda-Chains - genetics; Immunoglobulin lambda-Chains - immunology; Immunoglobulin Variable Region - genetics; Immunoglobulins; Light; Loci; Mammals; Medical research; Medicine and Health Sciences; Monoclonal antibodies; Pharmaceuticals; Poultry; Progranulins - immunology; Proteins; Research and Analysis Methods; T-Lymphocytes - immunology; Transgenes - genetics; Transgenic animals; United Kingdom; United States > US; California
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0228164

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 Vλ-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 Vκ-expressing OmniChickens. Kinetic analysis identified binders in the picomolar range. The Vλ-expressing bird increases the antibody diversity available in the OmniChicken platform, further enabling discovery of therapeutic leads.