by Alison Davis
April 16, 2004

Botulinum toxin (BT) is the single most poisonous substance known, with very small amounts causing paralysis and death². Botulism, the illness caused by this bacterially produced toxin, typically results from eating contaminated food. Cases of botulism are rare, but concerns about the possible use of BT as a bioterrorism agent have brought a new urgency to research in this area. Of special interest is the effect of inhaling the toxin.

Biochemist Lance Simpson, Ph.D., of Jefferson Medical College in Philadelphia concluded that inhaling BT can cause poisoning when the toxin travels from the airways to the bloodstream, where it does widespread damage to the body. He also discovered that a piece of the BT protein called the heavy chain was an effective inhaled vaccine in experimental mice. Simpson vaccinated the mice with the BT heavy chain and then injected them with a dose of BT estimated to be the same as if the animals had inhaled large amounts of the toxin. The BT heavy chain protein did not appear to harm the mice, and it stimulated their immune systems to produce protective antibodies against the toxin.

Simpson's work has immediate clinical relevance in suggesting ways to manufacture a human vaccine against this potential bioterror weapon. Even better is that the vaccine might be able to be administered by inhalation, not injection. While an antitoxin to neutralize BT circulating in the bloodstream is available, quantities of this remedy are insufficient to rapidly treat large numbers of people. More importantly, an antitoxin cannot enter poisoned nerve cells, limiting the usefulness of such a strategy. A safe and effective inhalation vaccine could circumvent these problems.

² Fact sheet on botulinum toxin produced by the Center for Biosecurity at the University of Pittsburgh Medical Center (2003)