Banana medicine

What will the vaccines of tomorrow look like? Recent advances in crop technology mean that we are able to produce vaccines in plants. But would you eat a vaccine? Harriet...
04 May 2009

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Think about it - the ideal vaccine: needle-free and it includes one of your five-a-day. Eat FruitBut what are the motivations for edible vaccines, and could they one day become standard practise?

GM controversy

Consumers everywhere are clamouring for natural foods free from genetic modification (GM), but what about a GM potato that could save your life? Altering the properties of crops is not a new phenomenon. Our ancestors chose the best crops with the best yields to breed the "super crops" which we rely on for foods today but now biotech companies are taking things a step further by using genetic modification (manipulating the genetic make-up of a plant) to short-circuit the breeding process and add desirable traits that can even turn plants into "vaccine factories".

Several approaches have been taken. In some cases the DNA sequences encoding antibodies (a molecule which is able to recognise a disease-causing agent) have been inserted into the genomes of plants, enabling the plants to produce the antibodies in their cells. These can then be harvested and purified for therapeutic use, or even just consumed alongside the rest of the plant, releasing the antibodies in the process.

Dirt Cheap

In 2002 it was estimated that as little as $0.005 could grow enough antigen for one dose of hepatitis B vaccine in an unprocessed form. Such cheapness would benefit vaccine programmes for rarer diseases or diseases which are not so financially rewarding for pharmaceutical companies (i.e. diseases which do not affect developed countries). There is also the potential to "grow" several vaccines simultaneously, producing the edible plant-equivalent of MMR, the combined measles, mumps and rubella jab.

There are other advantages too. Oral vaccines have the benefit of providing what is termed "mucosal immunity". This is the means by which the immune system defends sites such as the mouth, eyes, intestines and urogenital tract, usually through the production of secreted IgA antibodies. Some needle-administered vaccines produce only very weak protection at these sites, so this can be a major attraction.

Mass production is another bonus of oral vaccines - if we run out, we can simply plant more. The efficiency of these crops is also very high. According to Arizona State University researchers Charles Arntzen and Richard Mahoney "enough hepatitis B antigen to vaccinate all [the] babies in the world each year could be grown on roughly 200 acres of land". Plant-derived vaccines also have no requirements for energy-hungry refrigerators, the provision and maintenance of which can also hamper vaccination efforts in developing countries.

Feed the world

Undeniably, parts of the third world could use a cheap vaccine. Many thousands of children will die before their 5th birthday due to hunger and disease. Already some GM food crops are being trialled in these countries, modified in such a way to deal with difficult conditions such as drought. An oral vaccine given in these countries would not only protect the individual, but would also guarantee some form of nutrition for these infants. Importantly, such oral vaccines do not require refrigeration, cutting down on high distribution costs incurred by other vaccines. It also enables the vaccine to be carried safely to rural areas with limited access.

The lack of needles is not only important for the needle phobic. Needle administered vaccines are plagued with problems of re-use, mis-use and an occasional lack of sterilisation. With oral vaccines, infection risks would be very small. Giving an oral vaccine would require little or no training at all, which reduces the significant cost of vaccination programmes which require trained professionals.

Vaccines on a plate?

Before you get your recipe book out, there is a small restriction to the use of these truly 'super-foods'. Antibodies are sensitive to temperature, and so the material would have to be eaten raw. Dr Julian Marr (one of the leading scientists in this field) produces his vaccine against oral bacteria in a potato- one that must not be cooked! However, this crunchy vegetable is not the only option; there are potential vaccine candidates in bananas, maize, tomato and tobacco plants.

Another problem is ensuring the vaccine survives the digestive processes of the gut. One possible method would be to use attenuated (i.e. rendered harmless) strains of gut bacteria such as Salmonella. However, as with any attenuated organism, this could carry some risk. An alternative method would be to encapsulate the antibodies so that they are protected from the digestive chemicals in the gut. One option would be to naturally encapsulate the antibody within seeds- which are slowly digested.

One aspect that biotechnology companies would also need to consider would be how effective these vaccines actually are. Currently, most experimental vaccines do not provide adequate protection with just one dose, and biotech companies are looking at ways to boost this immune response. The immune response could be increased by adding an adjuvant (i.e. another chemical which boots the immune response).

The forbidden fruit?

However, these wonder-plants are not without their critics. Dr. Joe Cummins, Emeritus Professor of Genetics at the University of Western Ontario warns against the problem of horizontal gene transfer (where genes can transfer from one species to another) in these plants. Could we end up making the problem worse or cause resistance to the vaccine? "People subject to persistent exposure to the [HPV] crop vaccine are likely to develop oral tolerance, rendering them susceptible to virus infection," he says.

Progress in developing the vaccine has also been slow with many biotech companies holding back due to doubts over whether they will achieve a significant return and concerns over the regulatory process and licensing. In addition, there is, at best, limited human clinical trial data, which will be needed establish the correct dosage, timing and possible side effects of these vaccines.

Not quite 5-a-day?

So what does the future hold for the vaccine that doubles as a snack? Certainly the day when we all reach for a mouthful of a fruity lifesaver is probably still some way off, but the initial research has provided a tantalising taste of the potential of this technology. Could you be getting your next vaccine in the fruit and veg aisle at Tesco's? Watch this space.

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