A European Union (EU)-funded research project has opened up a radical new era in the world of vaccine discovery and production. Focused on veterinary vaccines, the project's work has made possible a dramatically faster and more effective route to the creation of vaccines to combat some of the most devastating diseases affecting farm livestock. The same accelerated route can be used to uncover a vast new range of urgently-needed vaccines for humans as well.
Named PLAPROVA (Plant Production of Vaccines), the project was the successful result of an unprecedented co-funding initiative between the EU and Russia, with Russia matching the €2 million of funding provided by the EU under its 7th Framework Programme. Consisting of six research teams from various EU countries, four from Russia and one from South Africa, the PLAPROVA consortium focused on the use of plants proteins to produce vaccines against diseases such as avian flu, bluetongue, foot and mouth disease, and porcine reproductive and respiratory syndrome.
Plants have been used to produce pharmaceuticals in the past, but the crucial element at the heart of the three-year PLAPROVA project was a technique for doing this much more quickly than previously possible – an advance which has revolutionary implications for future vaccine production. It also helped win a major innovation award for the lead researcher.
Known as 'transient expression', the method developed by the PLAPROVA group involves introducing a modified virus, which has been engineered to contain specifically chosen genes, into the leaf of a plant. This triggers the production of proteins which are of potential pharmaceutical interest as the basis for new vaccines. In contrast with previous methods, which required the genetic transformation of the entire plant to produce a protein - and which took years to produce a single protein in any sufficient quantity – the procedure developed by the PLAPROVA team can produce large quantities of new plant proteins in a matter of just weeks.
In the words of PLAPROVA's Project Coordinator, Professor George Lomonossoff of the John Innes Centre in the UK, the new technique turns the host plants into 'mini-factories', but without resorting to permanent genetic modification of the entire plant. The foreign genes that are transiently introduced are not inherited by subsequent generations of the plant.
The crucial advantage of PLAPROVA's method is that researchers are now able to produce and assess large numbers of proteins in a very short space of time, thus opening up much wider possibilities for genuinely novel vaccines. Previously, the timescale required before results were known for just a single protein meant researchers naturally played safe and tended to produce 'biosimilars', i.e. vaccines which replicated already existing ones. It was a situation which discouraged the search for new products.
Now, says Professor Lomonossoff, that has all changed: "You don't have to place all your money on one particular construct, then wait five years and hope you made the right selection," he says. "The great thing is, you get your failures quickly. If you are not sure which of 20 options will be best, you can just try all 20 and then select. You can be much more adventurous."
The speed of the new process is also a critical factor when dealing with seasonal outbreaks when a vaccine needs to be created urgently, usually in a matter of months from the time the strain of disease is first indentified.
The success of PLAPROVA has already generated significant commercial interest. Discussions are in progress with vaccine manufacturers in South Africa about production of a bluetongue vaccine. And a Canadian firm, Medicago Inc, has successfully applied the technique to the discovery and production of pandemic flu vaccines for humans, on which it has recently completed a Phase II clinical trial.
The revolutionary impact of the new PLAPROVA technique, with the possibilities it opens up for future work in vaccine discovery, was recognised with the naming of Professor Lomonossoff as Innovator of the Year 2012 by the Biotechnology and Biological Sciences Research Council (BBSRC), UK.