Robust production of virus-like particles and monoclonal antibodies with geminiviral replicon vectors in lettuce
Article first published online: 26 AUG 2011
© 2011 The Authors. Plant Biotechnology Journal © 2011 Society for Experimental Biology, Association of Applied Biologists and Blackwell Publishing Ltd
Plant Biotechnology Journal
Volume 10, Issue 1, pages 95–104, January 2012
How to Cite
Lai, H., He, J., Engle, M., Diamond, M. S. and Chen, Q. (2012), Robust production of virus-like particles and monoclonal antibodies with geminiviral replicon vectors in lettuce. Plant Biotechnology Journal, 10: 95–104. doi: 10.1111/j.1467-7652.2011.00649.x
- Issue published online: 6 DEC 2011
- Article first published online: 26 AUG 2011
- Received 27 April 2011; revised 2 July 2011; accepted 7 July 2011.
- geminiviral replicon system;
- plant vaccine;
- plant antibody;
- West Nile virus;
- Ebola virus
Pharmaceutical protein production in plants has been greatly promoted by the development of viral-based vectors and transient expression systems. Tobacco and related Nicotiana species are currently the most common host plants for the generation of plant-made pharmaceutical proteins (PMPs). Downstream processing of target PMPs from these plants, however, is hindered by potential technical and regulatory difficulties owing to the presence of high levels of phenolics and toxic alkaloids. Here, we explored the use of lettuce, which grows quickly yet produces low levels of secondary metabolites and viral vector-based transient expression systems to develop a robust PMP production platform. Our results showed that a geminiviral replicon system based on the bean yellow dwarf virus permits high-level expression in lettuce of virus-like particles (VLP) derived from the Norwalk virus capsid protein and therapeutic monoclonal antibodies (mAbs) against Ebola and West Nile viruses. These vaccine and therapeutic candidates can be readily purified from lettuce leaves with scalable processing methods while fully retaining functional activity. Furthermore, this study also demonstrated the feasibility of using commercially produced lettuce for high-level PMP production. This allows our production system to have access to unlimited quantities of inexpensive plant material for large-scale production. These results establish a new production platform for biological pharmaceutical agents that are effective, safe, low cost, and amenable to large-scale manufacturing.