Expression of human lambda expands the repertoire of OmniChickens

PLoS One. 2020 Jan 29;15(1):e0228164. doi: 10.1371/journal.pone.0228164. eCollection 2020.

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 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified / genetics*
  • Animals, Genetically Modified / immunology
  • Antibodies, Monoclonal / genetics
  • Antibodies, Monoclonal / immunology
  • B-Lymphocytes / immunology
  • Chickens / genetics*
  • Chickens / immunology
  • Humans
  • Immunity, Humoral
  • Immunoglobulin Heavy Chains / genetics
  • Immunoglobulin Variable Region / genetics
  • Immunoglobulin lambda-Chains / genetics*
  • Immunoglobulin lambda-Chains / immunology
  • Progranulins / immunology
  • T-Lymphocytes / immunology
  • Transgenes / genetics

Substances

  • Antibodies, Monoclonal
  • Immunoglobulin Heavy Chains
  • Immunoglobulin Variable Region
  • Immunoglobulin lambda-Chains
  • Progranulins

Grants and funding

Neither Carterra, Inc or Ligand Pharmaceuticals Incorporated played a role in the study design, data collection and analysis, decision to publish or preparation of the manuscript. Both organizations provided only financial support in the form of salary and research materials.