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June 3, 2002, 10:24PM

UT creates antibody to anthrax

Research could thwart terrorists

By LEIGH HOPPER

Copyright 2002 Houston Chronicle Medical Writer

Researchers at the University of Texas at Austin who study anthrax have developed a potential life-saving countermeasure: a genetically engineered antibody that binds to one of the anthrax toxins, preventing it from invading the body's immune cells.

The research is published in the June edition of the journal Nature Biotechnology.

"It's a smart strategy," said Johnny Peterson, a microbiologist at UT Medical Branch at Galveston who is conducting similar research. "As biologists, if we want to do something to interrupt the

(disease-causing) mechanism, we find a target."

One of the reasons anthrax is attractive to bioterrorists is that its victims may be on the brink of death even before the infection is discovered.

In cases of inhalation anthrax, the most lethal form of the disease, the anthrax bacterium itself is not the worst problem, initially causing nothing more than flu-like symptoms. It's the fatal toxins released by the anthrax microbes that flood the body, causing swelling, respiratory distress and death.

In a series of experiments conducted last summer, laboratory rats given a lethal dosage of anthrax toxin were able to survive if they were injected with the synthetic antibodies.

Scientists made the antibodies by isolating thousands of potentially useful protein fragments from mice. Using a process known as "laboratory-directed evolution," they isolated the best mouse antibody in the mixture. The antibody, called 1H, was found to bind 50 times more tightly to the toxin than any antibody known to the scientists.

That "sticky" quality enabled the antibody to hang on to the toxin long enough for it to be eliminated from the body.

Further tests will be conducted in monkeys, using a human antibody engineered to stick to the toxin, under conditions more closely mimicking the way anthrax is contracted. Researchers said it will take several years before a drug for humans can be made.

Jennifer Maynard, who participated in the research as a doctoral candidate in chemical engineering at UT-Austin, said her team's approach has a couple of advantages over strategies being pursued elsewhere.

For one, the antibodies can be grown easily and in large quantities. In addition, there is a long history of using antibodies to neutralize toxins. For example, people who have been bitten by a snake are given antibodies from a horse that has been injected with snake venom.

"It works exactly the same way," said Maynard, who is now studying infectious diseases at Stanford University. "We know a lot about this type of molecule."

The research was funded by the U.S. Department of Defense.

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