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High Level Production of Monoclonal Antibodies Using an Optimized Plant Expression System
Andrew G Diamos1,2, Joseph G L Hunter1,2, Mary D Pardhe1,2
1Center for Immunotherapy, Vaccines and Virotherapy, The Biodesign Institute, Arizona State University, Tempe, AZ, United States.
Frontiers in Bioengineering and Biotechnology
|February 4, 2020
Summary
Plant-based expression systems efficiently produce complex biopharmaceuticals like antibodies. Optimized geminiviral vectors enable high yields of therapeutic proteins, including a potent Zika virus neutralizing antibody, offering a cost-effective production method.
Area of Science:
- Biotechnology
- Molecular Biology
- Plant Science
Background:
- Biopharmaceuticals, particularly antibody therapeutics, represent a significant market share.
- Mammalian cell-based systems are traditional for antibody production but have limitations.
- Plant-based expression systems offer advantages for producing complex proteins.
Purpose of the Study:
- To demonstrate advances in plant transient expression systems using optimized geminiviral vectors.
- To showcase the efficient coexpression and high-yield production of heteromultimeric proteins.
- To validate the system for producing functional antibodies, including a broadly neutralizing anti-flavivirus antibody.
Main Methods:
- Utilized optimized geminiviral vectors for transient expression in plants.
- Coexpressed two, three, or four fluorescent proteins to assess yield and efficiency.
- Engineered and produced a chimeric broadly neutralizing anti-flavivirus antibody (2A10G6) by fusing murine variable regions to human IgG1.
- Employed a simple one-step purification process for antibody recovery.
Main Results:
- Achieved high yields of fluorescent proteins (3-5 g/kg leaf fresh weight), constituting ~50% of total soluble protein.
- Successfully produced a chimeric anti-flavivirus antibody at 1.5 g/kg leaf tissue.
- Demonstrated that the plant-produced antibody retains its ability to recognize the Zika virus envelope protein and potently neutralizes the virus.
- Produced two additional monoclonal antibodies at comparable levels (1.2-1.4 g/kg).
Conclusions:
- Optimized plant transient expression systems using geminiviral vectors are effective for high-yield production of heteromultimeric proteins.
- This technology provides a versatile, fast, powerful, and cost-effective platform for pharmaceutical multi-protein complex production.
- Plant-based antibody production offers a viable alternative to traditional methods, with demonstrated therapeutic potential.
