"we are still far from knowing if this approach will eventually produce safe and efficacious vaccines for humans... the number of non-responders is much higher than that observed with the conventional vaccine". - Martin Friede at the World Health Organization's Initiative for Vaccine Research
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Potato-based vaccine success comes too late
Andy Coghlan
NewScientist.com, 14 February 2005
http://www.newscientist.com/article.ns?id=dn7006

Genetically engineered potatoes containing a hepatitis B vaccine have successfully boosted immunity in their first human trials.

But the newly-published study missed a moving target - drug developers are now abandoning their quest for vaccines contained in staple foods like bananas, tomatoes or potatoes.

The hope was that the altered foods would provide a cheap source of vaccines that could be grown and administered in poorer countries without the need for costly refrigeration or needle injections. However, developers have changed tack to avoid any possibility of vaccine-laden food straying into shops or markets. If this occurred, it could be unwittingly eaten by consumers, with unpredictable results.

Instead, developers are now focusing on making vaccines in the safely edible leaves of plants not on sale as food.

"We've not worked with potatoes for two years now," says Charles Arntzen at Arizona State University in Tempe, US, who led the potato study and is a veteran of the decade-long bid to produce GM vaccines in foods. "We don't say 'edible' vaccine any more - we say 'heat-stable oral vaccines'."

Ground-up leaves

Arntzen and his colleagues have remained focused on making oral vaccines, but this time using ground-up leaf tissues, administered in gelatine capsules - the same format as conventional pharmaceuticals.

"We're doing all the animal studies now," says Arntzen. A number of plants are being investigated, but the best results so far have been in Nicotiana benthamiana, a relative of tobacco already widely used in research, but previously not eaten. "There's no edible use of it at all," he says.

The leaves are harvested, washed, ground-up and freeze-dried for preservation before packaging in capsules. The freeze-drying means they survive in hot climates, avoiding the need for refrigeration which hampers delivery of conventional, heat-sensitive vaccines.

The approach also means that the vaccine can be delivered in uniform doses, making it more likely to win approval from regulators.

Finely-chopped chunks
Despite abandoning the potatoes, Arntzen says he is proud of the results, and that they support the principle of oral vaccination.

In the study, the volunteers all ate finely-chopped chunks of raw potato. Some ate potatoes in which a major surface protein of the hepatitis B virus had been produced, while others received unaltered potatoes.

More than 60% of the volunteers who had three doses of the vaccine made a large number of extra antibodies against the viral protein, as did 53% on two doses. None of the volunteers eating ordinary potato generated new antibodies.

But all the recipients had previously received a conventional hepatitis B vaccine, so the potato vaccine was simply boosting immunity that was already present.

Sterner test

Arntzen acknowledges that giving the vaccine to unvaccinated volunteers would have been a much sterner test. But he claims that the results seen are still stunning with an oral vaccine consisting of only a protein. The only other effective oral vaccine is the one for polio, but that is a live, weakened form of the virus itself.

Additionally, an immune system stimulator usually administered with a vaccine was not given. All this bodes well for the leaf-based oral vaccines now in development, he says.

"We are very interested in the approach, and these results are very encouraging," says Martin Friede at the World Health Organization's Initiative for Vaccine Research. "But we are still far from knowing if this approach will eventually produce safe and efficacious vaccines for humans."

For example, Friede told New Scientist, "the number of non-responders is much higher than that observed with the conventional vaccine".

Journal reference: Proceedings of the National Academy of Sciences (DOI: 10.1073/pnas.0409899102)
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Charles J. Arntzen - GM Watch profile
http://www.gmwatch.org/profile1.asp?PrId=13

Arntzen is the founding Director of the Arizona Biomedical Institute (ABI) at Arizona State University (ASU).

The ABI forms a key means of achieving the ASU's goal of facilitating interactions with Arizona's biotechnology industrial base, and of dramatically expanding the ASU's external funding in areas like biotechnology. The ASU wants a particular focus on high-payoff areas that will help to expand economic development for the State's biotech sector.
http://researchnet.asu.edu/prop301/bio.html

Arntzen was previously the former President and CEO of the Boyce Thompson Institute for Plant Research, Cornell University, Ithaca, New York.

Arntzen has specialised in 'edible vaccines' genetically engineered into food plants such as tomatoes, bananas and potatoes.

Arntzen has bred potatoes that express Norwalk virus and E. coli antigens. Human test subjects have been fed the potatoes raw, because cooking might damage the antigen, even though cooking is normally considered necessary to render harmless the high levels of natural toxins that can occur in potatoes.

It also remains unclear how much vaccine a person would need to eat to ensure protection and how often, nor is it known how to avoid overdosing, or what side effects such as allergies may arise.

Like other plant biotechnologists, Arntzen has also found unexplained effects within plants he has genetically engineered. (Newsweek International, January 28, 2002)

In 1999 Arntzen attacked US company Frito Lay for bowing to consumer demands to make their snacks GM-free. Arntzen warned that consumers would boycott Frito Lay in punishment for denigrating GM 'crops that are helping make American agriculture more competitive on a global scale' (Top Producer magazine, December 1999). US farm exports have suffered multi-million dollar losses since the introduction of GM crops.