Through an innovative feat of plant biotechnology and vaccine design, researchers in the Biodesign Institute at Arizona State University have successfully turned tobacco plants into vaccine production factories to combat the deadliest form of plague.
The vaccine elicits a protective immune response in guinea pigs. The results are considered to be a milestone in the future development of a new vaccine for human use.
Plague, caused by a rod-shaped bacterium called Yersinia pestis, no longer invokes the "black death" feared throughout history, having been widely tamed since the advent of antibiotics. But a new concern has emerged in recent years with respect to bioterrorism.
"There have been discovered some resistant strains to antibiotics and that poses a concern, especially if plague would be used as a bioweapon," said Luca Santi, a research assistant professor at the institute and lead author of the study published in the early online edition of the journal Proceedings of the National Academy of Sciences. "A new vaccine approach would be the best way to prevent infection."
In addition to manmade threats, the Centers for Disease Control estimates 1,000 to 3,000 outbreaks still occur in the world every year as a result of people coming into close contact with rodents infected with fleas that harbor the bacteria.
Particularly worrisome to human health is the pneumonic form of the disease, which can spread by an airborne route after infecting the lungs. It is considered universally fatal if not detected and treated after symptoms arise one to six days after the initial exposure.
Current vaccines against plague are severely limited from widespread adoption by having problems with high adverse reaction rates and side effects.
The research team included Santi, Hugh Mason and Charles Arntzen, all members of the institute's Center for Infectious Disease and Vaccinology. They worked out a new plant-based system to rapidly and stably produce high levels of proteins, called antigens, which conferred immunity against the plague.
"This current work represents a new direction in our research because we've come to the realization that plants also have the potential for the production of antigens that can be purified and delivered by typical intramuscular or subcutaneous injections -- the way most vaccines are normally given," said Mason, an associate professor in the School of Life Sciences. "This new system produces really high levels of antigens in relatively short periods of time."
The researchers modified tobacco plants to make high levels of the plague antigens F1, V and a combination of the two, a so-called F1-V fusion antigen. All are known to be important for the plague bacteria to produce its toxic effects.
The antigens were purified from the plants and injected into guinea pigs. Testing using an aerosolized form of plague was performed by Chad Roy and Robert Webb at the U.S. Army Medical Research Institute of Infectious Disease at Fort Detrick, Maryland. This project was also the first comparison study designed to test more than one kind of antigen during the same challenge.
"The idea with any recombinant subunit vaccine is that you can pick and choose selective antigens that can confer protection and limit the potential for adverse reaction," said Mason.