Potato-based vaccine success comes too late - Lyophilization Articles & Reports

Potato-based vaccine success comes too late
April 26, 2005
Andy Coghlan
New Scientist
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".