Plant-based technologies for human and animal health
The production of large amounts of pure, properly folded, biologically active proteins is essential for the development of vaccines and diagnostic tools. Recombinant proteins for these purposes are currently produced using prokaryotic (for example, E. coli) or eukaryotic expression systems.
One of the problems of prokaryotic expression systems is that bacterial cells do not perform the same types of post translational modification as eukaryotes. Moreover, the interior of a bacterial cell may not conduct proper folding of eukaryotic proteins. This affects a protein’s activity, stability and response to antibodies and as a result, improperly folded and inactive recombinant proteins can be produced.
The use of plants as bioreactors for expressing proteins and extracting them in an active form opens up new opportunities for the production of pharmaceutical proteins. In the last few years substantial evidence has accumulated that plant-derived vaccines are economically and therapeutically advantageous.
The main advantages provided by plants as factories for foreign proteins production are (i) low cost of cultivation, (ii) short time frame for protein production, (iii) the technology is entirely safe, since only selected target proteins are produced as the vaccine protein, (iv) the protein production can be easily scaled up or down (without large additional costs) depending on demands.
EU FP7-funded PLAPROVA project
We have recently been involved in the EU FP7-funded project PLAPROVA to exploit transient expression systems developed by the partners that can produce significant amounts of candidate vaccine protein suitable for testing within weeks, rather than months. This €4 million EU-FP7 project consortium comprises seven key research teams in six EU countries, four teams in Russia and one team in South Africa. Initially, the consortium has concentrated on diseases of importance to farming in both the EU and Russia, which include avian influenza, blue tongue, foot and mouth disease and porcine reproductive and respiratory syndrome. Candidate proteins identified through this research programme will be developed for large-scale production and ultimately low-cost production of effective vaccines.
During the project we have developed an approach based on use of an Agrobacterium-mediated plant expression system carrying a self-replicating plant virus to produce high yields (185mg/kg fresh weight) of the bovine papilloma virus (BPV) capsid protein, which self-assembles into virus like particles (VLPs) within the plant. BPV is an economically important virus that induces tumorigenic pathologies in horses and cows. The VLPs produced at TJHI can be used not only as a potential vaccine for BPV but also as a scaffold for the presentation of epitopes of other important pathogens.
New DEFRA grant on the development of diagnostic tools and vaccines to control sheep scab
Another successful example of our research in this area is sheep scab mite. Sheep scab seriously affects the welfare of sheep and is a widespread problem in the UK. A new grant has been awarded by the Moredun Research Institute to develop novel strategies to control sheep scab using immunological approaches and the development of diagnostic tools. The James Hutton Institute team led by Professor Michael Taliansky has joined Moredun Research Institute as a sub-contractor to ensure the sufficient production in plants of recombinant proteins which will be used for both diagnostic and vaccine purposes.
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