When diagnosed in time, anthrax can be cured by giving large doses of antibiotics. But when treatment is started too late, patients often die: not from Bacillus anthracis bacteria itself, but from their toxin, which wreaks havoc even after the bugs have been killed. Now, researchers have come up with a second line of defense by creating potent antibodies that stop the toxin in its tracks.
The anthrax toxin has three components. One, called protective antigen (PA), latches onto the surface of immune cells called macrophages and shuttles the other two components--edema factor and lethal factor--into the cells. Antibodies harvested from the plasma of people vaccinated against anthrax can interfere with this process (ScienceNOW, 1 February), but the yield is low and many of the antibodies are not specific for the toxin. Now, biochemist Brent Iverson and protein engineer George Georgiou of the University of Texas, Austin, have created a new type of antibodies that specifically interrupt the docking process of PA.
Their team cloned the genes for fragments of binding region of the mouse anthrax antibody in a virus and improved their affinity for PA by repeatedly generating variants and picking out the ones that bound PA best. They ended up with fragments that stuck to PA 50 times more tightly than the original fragments and more tightly than most natural antibodies, they report in the June issue of Nature Biotechnology. And the fragments proved their worth: Whereas unprotected rats died 1.5 hours after they had been given 10 times the lethal dose of anthrax toxin, rats injected with the antibody fragments survived for 5 hours--enough time, the researchers say, for the kidneys to filter the antibody-bound toxin out of the bloodstream. Georgiou now plans to engineer the protective antibody fragment into human antibodies. Those could be tested for efficacy in human patients if bioterrorists strike again, he says.
Anthrax researcher Philip Hanna of the University of Michigan, Ann Arbor, says these results are "reassuring." Humanized antibodies may be useful in the treatment of anthrax, he says, along with antibiotics. But the next question--and the most important one, says Hanna--is whether these designer antibodies protect not just from a toxin shot, but also from the real thing: an infection with inhaled spores. "The bugs grow rapidly," says Hanna, "and they know other tricks besides the toxin."
Related sites
Iverson's
site
Georgiou's
site
Anthrax info
from the Centers for Disease Control and Prevention
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