Aug. 11, 2000 -- It's vaccination time, but no needles are needed. You hand your child's prescription to the pharmacist, and she gives you a bottle of tomato juice -- or applesauce, or spinach, or rice, or maybe a dried vegetable powder. Today, bio-engineered plants are being used as inexpensive factories to manufacture vaccine ingredients. Tomorrow we may be eating the plants themselves.
By infecting them with genetically altered plant viruses or bacteria that can't cause disease but can reproduce, scientists can make plants produce large quantities of many different kinds of substances -- including vaccines.
The idea fascinates vaccine pioneer Hilary Koprowski, a key player in the development of the oral polio vaccine and inventor of the modern rabies vaccine. Koprowski has been working on plant-derived vaccines for the past decade. He is now director of the Biotechnology Foundation Laboratories and the center for neurovirology at Jefferson Medical College at Thomas Jefferson University in Philadelphia.
"Why plants? Three things," Koprowski tells WebMD. "Reason No. 1 is extremely good safety -- there is nothing in plants that can contaminate the vaccine [and make humans sick]. The plant viruses we use cannot infect mammals, including humans. Second, the cost. You do not need a factory to grow a plant. Third, the ease of distribution. You could easily make a freeze-dried vegetable powder."
It's not science fiction. One virus on the defensive is respiratory syncytial virus, or RSV -- the single most important cause of respiratory infection in infants and children throughout the world, which causes an illness commonly referred to as croup. An injectable vaccine against RSV was a spectacular failure -- vaccinated children actually got a worse disease because the vaccine stimulated the wrong kind of immunity. Dennis E. Buetow, PhD, and co-workers at the University of Illinois at Urbana-Champaign have created engineered cherry tomatoes that appear to elicit the right kind of immune responses in mice.
"Our idea is to prevent RSV infection," Buetow tells WebMD. "We are thinking that you would eat the fruit at some time preceding each RSV season. The reason we began with the cherry tomato is that we are thinking about the apple. Of course, growing fruit trees is a three- to five-year process, so we wanted to see whether it would work in cherry tomatoes first."
It won't take years to grow orchards in all cases. One firm -- Large Scale Biology Corp. -- already has built a factory capable of processing three tons of plant material per hour. "Plants will grow anything," Koprowski says. "The state of the art is that a large number of labs all over the world" are trying to use plants to produce a lot of vaccines, hormones, cancer fighting substances, and blood products. In 10 years you will have a lot of plant-derived human products available, predicts Koprowski.
Koprowski has worked with a Polish research team that has grown a vaccine against the hepatitis B virus in lettuce. After eating the lettuce, the immune systems of human volunteers started fighting the hepatitis B virus, which causes severe and sometimes fatal liver disease.
Another exciting product is a vaccine that would be used to treat patients with incurable leukemia, a form of blood cancer. Renowned cancer specialist Ronald Levy, MD, chief of the division of oncology at Stanford University in Palo Alto, Calif., developed the vaccine and hopes to begin human tests of the plant product this fall. Because of differences in the tumors between leukemia patients, each vaccine will have to be individualized. Making such a vaccine with conventional techniques takes the better part of a year -- but it takes only six to eight weeks to produce it in a tobacco plant.
"We've been doing clinical trials for about 10 years now, producing [the vaccine] in a variety of ways," Levy tells WebMD. "The plant system has the potential advantage of convenience, simplicity, and perhaps even [strength]."
The strength of the vaccine is a major issue and is one reason why scientists continue to seek plant vaccines that can be eaten, unlike those produced by a tobacco plant, which presumably would have to be inhaled. Oral vaccines stimulate different kinds of immune system responses than their injectable cousins -- and these kinds of immunity can protect the membranes of the nose and mouth where most germs, including RSV, first enter the body.
One of the main goals of Buetow's team is the creation of a vaccine that is affordable for poor nations. "It should be readily adaptable to almost any place that needs it," he says. "That would take care of any problems with shipping -- just grow it locally."
Charles E. Rupprecht, PhD, VMD, chief of the rabies section at the CDC's National Center for Infectious Diseases, agrees that affordability is indeed a major issue driving plant vaccine research. "It's a question of the haves and the have-nots," he says. "Most of the risk is in the developing countries that can't afford current vaccines."