Effective, Safe Anthrax Vaccine Can Be Grown In Tobacco Plants

Mice immunized with a vaccine produced in UCF professor Henry Daniell's laboratory through the genetic engineering of tobacco plants survived lethal doses of anthrax administered later by National Institutes of Health researchers. The results of the NIH-funded study are featured in the December issue of the Infection & Immunity journal.

Daniell's research is a breakthrough in efforts to find a safe and effective method of producing large quantities of vaccine for anthrax, one of the top bioterrorism threats facing the United States. The new production method also could help the government and health care providers avoid supply shortages, as one acre of plants can produce 360 million doses in a year.

"Anthrax vaccine is very much in need, primarily because of bioterrorism concerns," Daniell said. "But in the United States, only one company has the capacity to produce the vaccine, and it is made in very small quantities by fermentation. We can provide enough doses of a safe and effective vaccine for all Americans from just one acre of tobacco plants."

Current production of the vaccine involves an expensive fermentation process that can cause harmful side effects such as inflammation, flu-like symptoms and rashes. This has prompted some people to refuse to be vaccinated.

Seeking a safer and more effective alternative, Daniell and his colleagues injected the vaccine gene into the chloroplast genome of tobacco cells, partly because those plants grow much faster than carrots, tomatoes and coffee. They grew the cells for several weeks in Daniell's laboratory. Tests showed the vaccine taken from the plants was just as potent as the one produced through fermentation but lacks the bacterial toxin that can cause harmful side effects.

Researchers then injected the vaccine into mice to immunize them against anthrax and sent the mice to NIH labs, where they survived doses of anthrax several times stronger than the amounts to which humans have been exposed.

The next step for the anthrax vaccine would involve a company working with NIH to conduct clinical trials. Human subjects would be injected only with the vaccine and not with anthrax itself, and scientists would then check the subjects' immunity levels. The vaccine later could be mass-produced and stockpiled for emergencies.

Daniell conducted his study with part of a $1 million NIH grant and a $2 million U.S. Department of Agriculture grant that cover research related to genetic engineering in plants as a way to produce therapies for several diseases. Daniell's work holds promise for treating other diseases, including diabetes and hepatitis, and improving vaccines for plague, cholera and other bioterrorism agents.

Daniell is developing a new technology that would enable vaccines to be administered orally and allow effective and less expensive treatments to be more accessible worldwide. He believes fruits and vegetables such as carrots and tomatoes are the keys to figuring out a way for people to take anthrax vaccines orally in capsules of dried plant cells that contain correct doses of the protective antigen.

If that research is successful, the needs for requiring doctors to administer the shots and for shipping vaccines in refrigerated trucks, both of which can be especially difficult in poorer nations, would be eliminated.

The military now administers the vaccine with three shots in the first four weeks, three more in the next 17 months and then annual booster shots, according to the Pentagon (www.anthrax.mil).

Daniell, who is the first UCF Trustee Chair in Life Sciences, began teaching at UCF in 1998. He has formed a biotechnology company called Chlorogen to apply his work in chloroplast genetic engineering. In 2004, he won UCF's Pegasus Professor Award, the top honor given to a faculty member who excels in teaching, research and service. Last year, he also became only the 14th American in the last 222 years to be elected to the Italian National Academy of Sciences.

The research team for the anthrax project also included Vijay Koya, a graduate student in Daniell's lab, and Mahtab Moayeri and Stephen H. Leppla of the Microbial Pathogenesis Section of the National Institute of Allergy and Infectious Diseases at NIH.