Fending off the plague: ASU generates plant-made vaccine to fight bioterrorism

TEMPE,Ariz.—Combining lessons in plant biology and vaccine generation, scientists atArizonaStateUniversity's (ASU's) Biodesign Institute have engineered tobacco plants to produce vaccine antigens against the microbe that causes the legendary Black Death, Yersinia pestis. In doing so, they have taken another step toward helping the world protect itself from bioterrorist attack.

"The current vaccine for plague is not very effective and produces frequent adverse reactions, because it is a killed, whole-cell vaccine," says Dr. Hugh Mason, ASU professor. "Our work extended the work of others showing that one or two antigens from the bacterial cells can be produced as 'subunit vaccines' in recombinant systems, purified, and injected to produce protective immunity."

What makes this effort particularly different from the others is Mason's reliance on plants to produce the bacterial antigens that form the basis of the vaccine. Describing their efforts in a recent issue of PNAS, the researchers used the magnICON system from their collaborators at Icon Genetics, based inMunich,Germany, to modify tobacco mosaic virus to produce the pathogen peptides upon infection of tobacco plants. They then tested the vaccine candidates in guinea pigs and found they conferred strong resistance to Y. pestis.

The Biodesign Institute's efforts are part of a larger trend by academics and corporations to pursue plant-made pharmaceuticals (PMPs). According to Anne Anscomb, an analyst with Kalorama Information, PMP development is progressing steadily, if slowly, through the regulatory process both in theUnited StatesandEurope. She adds that the first transgenic PMP— Planet Biotechnology's CaroRX, which targets dental caries—could get market approval from the EMEA this year.

"Plants have the potential for immense-scale production," Mason says. "Furthermore, plant production limits the chance of contamination with bacterial components or animal viruses, in the case of vaccines produced in animal cells."

Unlike most other PMP attempts, Icon Genetics and the Biodesign Institute chose to focus their efforts on viral infection rather than transgenically modified plants for the sake of product speed and yield. According to Mason, viral systems can be developed in a matter of weeks, whereas transgenic plant lines may take months or years to create and fully characterize. Likewise, viral systems can produce incredibly high yields, up to 80% of total soluble protein, while transgenics often only produce 1% of total soluble protein.

Efforts like this are attracting interest in the drug discovery field. Says Annescomb: "Transgenic biotechnology companies will become attractive buyout targets for large pharma in their search to reduce drug production costs while expanding their market share." Along these lines, Bayer Innovation recently acquired Icon Genetics (see editconnect code E030606).

To move beyond the testing stage, however, cost-effective production will require a vertically integrated plant production and processing facility, says Mason, in which plants can be grown, infected with recombinant virus, harvested, processed, and antigens purified and formulated. "We are planning such a facility at ASU that would produce small lots of materials for use in Phase I clinical trials," he adds.

In the meantime, the group will continue to develop its system for a wider variety of pathogens and is in the process of developing an edible plague vaccine candidate that they describe in an upcoming issue of Vaccine. "Oral doses needed to produce an effect are much higher than by injection, but if mass production is easy, the convenience of oral delivery can outweigh the use of needles," Mason says.