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Antibody Cocktail Battles Botulism

Researchers have developed a potent weapon against the paralyzing disease botulism. The affliction results from exposure to botulinum neurotoxin (BoNT), which is secreted by a soil bacterium called Clostridium botulinum. The most poisonous substance known, just a gram of BoNT could kill a million people if evenly dispersed and inhaled. As such, it ranks among the Centers for Disease Control and Prevention¿s six highest-risk threat agents for bioterrorism. At the moment, no anti-botulism treatments capable of being produced on a large scale are available. But a new drug described in a report published online this week by the Proceedings of the National Academy of Sciences both neutralizes the toxin very effectively in mice and apparently can be readily mass-produced and stockpiled.

The drug consists of three antibodies, each of which binds to a different part of the botulinum toxin. Together they squelch far more of the toxin than they would individually. "This approach has allowed us to develop a drug consisting of only a few antibodies which neutralizes toxin better than the most potent natural immune response," says team member James D. Marks of the University of California at San Francisco. And because the antibody genes are cloned into a manufacturing cell line, cultured cells could conceivably churn out an unlimited supply of the antibodies.

So far, the researchers have shown the drug to work in mice against one of the four BoNT types known to cause botulism. But they suspect that such cocktails of multiple antibodies, or oligoclonal Abs, will one day combat a wide array of diseases caused by other pathogens and biologic threat agents. Indeed, the team concludes that its findings support "the rapid development and evaluation of oligoclonal Ab for countering BoNT and other agents of biowarfare and bioterrorism."

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