Agriculture, pharmaceuticals create even tighter bond as potato vaccine is developed.

While traveling in India, Dr Charles Arntzen came across a mother nursing a crying child.

But he noticed when the mother put a tiny morsel of food on the tip of her finger and fed it to the child, the baby stopped crying.

This sparked an idea in Arntzen, president of the Ithaca, NY-based Boyce Thompson Institute for Plant Research (BTI), which focuses on developing vaccines to be delivered through plants - if only vaccinating a child could be as easy.

Now, this concept is becoming a reality. A potato in which the vaccine for the Hepatitis B virus has been placed is scheduled to be grown as a pharmaceutical crop in Wisconsin by Delavan, WI-based American Ag-Tec International, Ltd., an agricultural technology company. Production and manufacturing agreements have been reached between Ag-Tec, BTI, and Cambridge, England-based Axis Genetics, a plant pharmaceutical company.

Tuber Technology
The agreement allows Ag-Tec to move ahead with the multiplication of the first-ever large-scale, pharmaceutical potato crop. In addition, not only is the success of this research a breakthrough in medical technology, but it also reinforces the importance of medical agriculture as a new worldwide industry and helps solidify the growing ties between ag and pharmaceutical companies as both combine to form life sciences companies.

"This is a major departure from what things have been in the past," says Robert G. Britt, Ag-Tec president, "not only in pharmaceutical vaccines but in the way potatoes are being grown."

Rapid multiplication minituber technology developed by Ag-Tec, branded as Quantum Tubers, is allowing for the accelerated production of these trial pharmaceutical potatoes. Traditionally, potato production involves the use of seed tubers that need to continually be monitored and evaluated for the presence of pathogens. Since before the turn of the century, those in the ag business have known that the use of high quality seed potatoes is the preferred method for preventing the decline in vigor, which occurs from the accumulation of pathogens when tubers are repeatedly recycled for "seed."

Since the early 1980s, the use of tissue culture methods has facilitated the production process of pathogen-free potato seed. But there was still a need for several production generations (usully five to seven) to multiply seed stocks for use by commercial growers. Quantum Tubers technology allows for pathogen-free, harvestable seed tubers to be developed in about 40 to 50 days, and then multiplied within two generations in the field (eliminating five field multiplications) to provide commercial quantities of seed potato.

This technology allows rapid multiplication of genetically engineered prototypes developed at BTI.

"The use of transgenic plants for production of edible vaccines represents a human interest application for the biotech industry," says Dwayne Kirk, BTI edible vaccines project manager.

Worldwide Benefits
Despite the protest concerning transgenic crops from anti-biotech crop groups worldwide, the true benefits of these farmed pharmaceuticals will be reaped by developing countries, which will be better able to afford these cheaper vaccines. And the recipients of the vaccines, often in remote locations, can be assured the edible vaccines are still safe and not heat-inactivated during shipping, Kirk says.

"Genetic engineering has allowed scientists to readily identify and clone a wide assortment of genes, including those which encode for various antigens (foreign proteins which the body recognizes and produces antibodies against) capable of immunization," he says. The proteins normally form part of the bacteria or virus structure - or the toxic proteins that pathogens produce during the course of infection.

Traditional vaccines have been effective through killed bacteria injected into the bloodstream, whereas this modern method removes the possibility of infection.

"By introducing that isolated gene into a foreign living system," Kirk says. "we can produce the same protein without any of the infectious DNA. This can be done in a plant tissue which doesn't need purification and is normally eaten in its natural form, as well as removing the expense of essential refrigeration."

Development of edible pharmaceuticals will, in a sense, revolutionize vaccination programs "by significantly reducing the cost of vaccine production and cost to the consumer," Kirk says. "It will allow greater access to vaccines for countries suffering under a poor economy. This technology has opened a new avenue of biotech research and further promotes the link between biotechnology and improved quality of life for humankind."

Major Challenges
Human trials for the potatoes now involve feeding raw potato cubes to volunteers, but the vaccine in its final edible form will more likely be a powdered potato, tomato paste, or dried banana chips.

When the potato is eaten, Kirk says, the rigid structure of the plant cell walls protects the antigen against the digestive enzymes and low pH in the stomach, until it can be slowly released in the lower gastrointestinal (GI) tract. The mucous linings of the lower GI tract contain specialized cells that can recognize certain types of foreign proteins, then in turn capture the proteins and present them to the body's immune system.

Only one published human trial test has been conducted (but many successful animal trials for several vaccines), so it can't yet be determined whether this method will work across a variety of vaccines. But if the technology for this method of vaccination proves successful, "It will certainly reduce the use of injected vaccines in favor of consumption of transgenic 'vaccine food,"' Kirk says.

The first human trial with potatoes containing a vaccine was completed in 1998. The raw vegetable stimulated specific antibody protection against diarrhea caused by E. coli contamination. Several clinical trials to evaluate other vaccines produced in potatoes are slated for this year.

A Long Road
Edible vaccines are unlikely to be available for at least another three years, after further testing and federal Food and Drug Administration (FDA) approval.

Even if the method takes off, the traditional needle and syringe is unlikely to become obsolete. "I would not anticipate the complete phasing out of certain injected vaccines," Kirk says. In fact, some vaccines may work better if the initial dose is injected but followed by boosting doses from transgenic plants. Immunization may be most effective if the same antigen can be provided by two different methods.

Since vaccine potatoes must grow under controlled conditions (like any other vaccine) and because they are "under the guise of a pharmaceutical product" - they won't be released for general commercial use. Kirk says.

Adds Britt: "It's important if we can prevent one more needle stick."

The Web site for American Ag-Tec is www.ag-tec.com.
End

Farm Chemicals Magazine, March 1999