Biomimetic plants offer rich vaccine harvest – In the field: pharmaceutical science & technology news
Kaylynn Chiarello
Many vaccines in use today aren’t suited to the needs of developing countries. Not only are traditional injectable vaccines expensive to produce, they must also be kept refrigerated from point-ofmanufacture to point-of-use. In regions where electricity is not readily available, it’s challenging to transport and deliver vaccines before they expire. A research team from the Center for Infectious Diseases and Vaccinology at Arizona State University (ASU, Tempe, AZ) is developing a novel manufacturing technology that could provide solutions for these problems.
The key to ASU’s unique approach is the use of genetically-altered plant material as the basis for vaccine formulations. Basing their technology on biomimetics, a technique that imitates natural mechanisms and processes, ASU’s team of 25 research scientists changes a plant’s genetic code to produce fruits that induce certain immune responses when consumed. Much like traditional vaccines that use yeast or eggs as surrogate hosts for viral pathogens, biomimetics transforms fruit-bearing plants into production lines for subunit vaccines by inserting genes for noninfectious viral protein segments into the plants cells. The genetically altered plant cells mature into cuttings that are planted and grown in soil to full-size plants.
After harvest, ASU’s team freeze-dries the fruit, grinds it into a powder, and inserts it into a capsule. “At this point, the capsule is a vaccine, formulated in a freeze-dried state in plant cells. With this powder we can treat it like any other pharmaceutical,” says Charles Arntzen, director of ASU’s Center for Infectious Diseases and Vaccinology. The entire process takes about 4-5 months to complete, making possible oral, heat-stable vaccines for the third world.
“Breaking the ‘cold chain’ is the key to this availability and is the group’s primary focus,” says Arntzen. “We’re saving enormous costs because the freeze-dried material doesn’t need to be refrigerated.” For the same reasons that plant seeds can lie dormant for long periods of time without losing their vitality, the plant-derived vaccines don’t need to be kept cold. “In a dehydrated state, plant cells’ enzymes, nucleic acids, and proteins are stable because they’re not subject to any sort of degradative activity. We’re mimicking a natural biopreservation system,” points out Arntzen.
In addition to saving money on refrigeration, ASU researchers will be able to manufacture an oral plant-derived vaccine for a fraction of the cost of traditional vaccines. “Our target is to make unit doses of oral vaccines at five cents per dose or less,” says Arntzen.
Since plants are also suitable sources of organic matter for excipients, scientists won’t need to spend time formulating the vaccine once the fruit is produced. Both the excipient and active ingredient would be “packaged” together within the genetically-altered fruit. “We’re skipping a step,” says Arntzen. “By using just the starches, proteins, and sugars that are naturally present in plant cells, the entire formulation will be inside the freeze-dried plant cells.”
Researchers are also addressing concerns that genetically-altered plants could intermix with other plants in the food chain. For example, they are using tomatoes as the host of their vaccines, and tomatoes don’t easily transfer their genetically altered genes to other plants. Additionally, all work on the genetically altered plants is performed in greenhouses to prevent cross-breeding with other crops.
To validate the technology, scientists from the Center for Infectious Diseases and Vaccinology have conducted three human clinical trials on the oral plant vaccines. In all tests, the appropriate immune response was produced. The researchers also recently received approval from the National Institutes of Health to perform a human clinical trial with a vaccine against diarrheal diseases. The study is expected to commence early in 2004.
Because millions of children living in developing countries die from diarrheal diseases each year, the research team chose to begin their studies with vaccines to treat Norwalk virus, cholera, and Escherichia coli. However, the oral, plant-derived vaccines have the potential to treat other types of bacterial and viral illness as well. “We’re continuing to work on an oral vaccine to treat hepatitis B and human papilloma virus. After this is achieved, measles may also be a suitable target for freeze-dried vaccines,” says Arntzen. Additionally, the Center is confident that its vaccine technology will be easily adapted to the production of veterinary vaccines for poultry, swine, and even household pets.
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