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Antibodies, also known as immunoglobulins, are produced by B cells in response to foreign substances, such as bacteria and viruses. These proteins are critical for recognizing and neutralizing these substances, protecting the body from potential harm.
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Area of Science:

  • Immunology
  • Molecular Biology
  • Biotechnology

Background:

  • Heavy chain-only antibodies (sdAbs) are naturally found in camelids and sharks, offering unique antigen-binding properties due to their smaller size.
  • Most vertebrates utilize conventional antibodies composed of both heavy and light chains, limiting the development of sdAb formats.
  • Investigating sdAb production in non-traditional species like chickens could broaden the scope of antibody engineering.

Purpose of the Study:

  • To engineer transgenic chickens capable of producing heavy chain-only antibodies (sdAbs).
  • To assess the development, expression, and functional capabilities of chicken-derived sdAbs.
  • To evaluate the potential of chickens as a novel platform for generating sdAbs.

Main Methods:

  • Generation of transgenic chickens lacking the light chain V region, retaining only the LC region for chaperone function.
  • Analysis of B cell populations, antibody repertoire diversity (IgM), and isotype switching.
  • Immunization of transgenic chickens with various protein immunogens and SARS-CoV-2.
  • High-affinity monoclonal antibody (mAb) recovery via single B cell screening and in vitro functional assays.

Main Results:

  • Transgenic chickens produced viable B cell populations and expressed chicken sequence sdAbs with a spontaneous CH1 deletion in heavy chains.
  • A diverse IgM repertoire was observed, with no isotype switching to IgY or IgA.
  • Immunization rapidly induced high, specific serum titers, and high-affinity mAbs were efficiently recovered.
  • Chicken-derived sdAbs demonstrated potent neutralization and prevention of SARS-CoV-2 replication in vitro.

Conclusions:

  • The truncated light chain design successfully enabled sdAb development and expression in chickens.
  • Transgenic chickens represent a viable and promising new host system for generating functional sdAbs.
  • Chicken-derived sdAbs hold significant potential for therapeutic and diagnostic applications, including against viral pathogens like SARS-CoV-2.