Tobacco mosaic virus (TMV) is one of the oldest known diseases of the plant world. Plague--known as the "black death" in medieval Europe--is one of the oldest diseases afflicting humans, and has become a focus of concern in recent years because of its potential use as a bioweapon. Now scientists have transformed TMV to infect host plants and produce immunizing proteins rather than debilitating leaf shrivel, turning greenhouse tobacco into a biofactory for plague vaccine.
Biotechnology specialists Charles Arntzen and his colleagues at Arizona State University used a process developed in Germany to effect the change. First, they injected the tobacco plants with TMV, genetically modified to produce one of three previously proven plague antigens: proteins known as F1, V and a fusion of the two. The three varieties of modified viruses quickly infiltrated the plants and replicated, but instead of producing infection, each viral cell started producing its assigned type of antigen. Within 10 days, the researchers had a full crop of tobacco leaves filled with vaccine. "Every time it replicates, it makes the proteins that we are interested in getting produced," Arntzen says.
Arntzen and colleagues then ground up the leaves--garnering roughly two milligrams of antigen for every gram of leaf--and purified the resulting vaccine with acids. Fellow researchers at the U.S. Army Medical Research Institute of Infectious Disease in Maryland then vaccinated groups of eight female guinea pigs with the different varieties of antigens before exposing them to Yersinia pestis--the bacteria responsible for airborne plague, the most potentially deadly form. Within six days, whereas all guinea pigs that had not been vaccinated were dead, nearly 60 percent of the vaccinated guinea pigs survived, and even those that died survived for longer than six days. The V antigen proved most effective, saving 75 percent of the inoculated guinea pigs.
Human testing remains to be done. But if the vaccine passes that test, it could provide an effective deterrent to emerging strains that have shown resistance to the antibiotics that have kept the deadly disease at bay in recent history. The findings are being published online this week by the Proceedings of the National Academy of Sciences.