anthrax spores. antibodies may be able to eliminate anthrax toxin after insects died.
When diagnosed in time, the coal can be cured by giving high doses of antibiotics. But when treatment is started too late, patients often die: not of Bacillus anthracis himself bacteria, but their toxin, which wreaked havoc even after the bugs were killed. Now researchers have developed a second line of defense by creating potent antibodies that prevent the toxin in its tracks.
The anthrax toxin has three components. A called protective antigen (PA), latches on the surface of immune cells called macrophages and shuttles the other two components - edema factor and lethal factor - in the cells. The antibodies harvested from the plasma of people vaccinated against anthrax can interfere with this process ( ScienceNOW February 1), but the yield is low and most antibodies are not specific to the toxin. Now, biochemist Brent Iverson and George Georgiou protein engineer from the University of Texas, Austin, created a new type of antibodies that specifically interrupt the docking process of PA.
Their team cloned genes for the fragments binding region of anthrax antibodies of the mouse in a virus and have improved affinity to PA by generating repeatedly variants and selecting those that bind best PA. They met with fragments that have stuck to PA 50 times closer than the original fragments and more closely than most natural antibodies, they report in the June issue of Nature Biotechnology . And fragments have proven their value: While unprotected rats died 1.5 hours after being 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 toxin bound to the antibody in the bloodstream. Georgiou now plans to design the protective antibody fragment in human antibodies. These could be tested for efficacy in human patients if bioterrorist strike again, he said.
Anthrax scientist Philip Hanna of the University of Michigan, Ann Arbor, said the results are "reassuring". Humanized antibodies may be useful in the treatment of anthrax, he said, with antibiotics. But the question - and most important, says Hanna - is whether these designer antibodies protect not only a stroke of toxin, but the real thing: an infection with inhaled spores. "Insects are developing rapidly," said Hanna, "and they know other things in addition to the toxin."
Related Sites
The site Iverson
the site Georgiou
Anthrax information from the Centers for Disease Control and Prevention
0 Komentar