Progress toward Disarming Anthrax

High-affinity antibodies to a component of anthrax toxin protect laboratory animals without help from antibiotics whether the animals are injected before or after being exposed to anthrax spores, according to chemistry professor Brent L. Iverson of the University of Texas, Austin. At the same time, the antibodies raise a basic question: Does this toxin component play a role in the conversion of anthrax spores to bacteria?

Iverson spoke at a symposium organized by the Division of Organic Chemistry during the American Chemical Society national meeting last week in Washington, D.C.

Currently, antibiotics are the major line of defense against anthrax. They are effective when taken immediately, before the anthrax bacteria secrete enough toxins to cause death. In the event of a clandestine attack, however, antibiotics may be administered too late. Once the toxins are released, antibiotics--which destroy the bacteria but not the toxins--will not stop the havoc the toxins wreak.

Iverson develops technologies to make better antibodies through a lab he jointly runs with colleague George Georgiou, a chemical engineer. In the late 1990s, a member of that lab, Jennifer A. Maynard, engineered an antibody for the anthrax toxin component called protective antigen. The antibody's efficacy is based on selective and high-affinity binding to protective antigen, which prevents the toxin from reaching its receptor. After showing promising results in toxin-challenge studies carried out by the Southwest Foundation for Biomedical Research (SFBR), in San Antonio, the antibody was licensed by Elusys Therapeutics, a New Jersey-based biopharmaceutical company specializing in antibody therapies for treatment of infectious diseases. Elusys turned it into a full immunoglobulin G (IgG), Iverson said.

Elusys has shown that the antibody protects rabbits before and after exposure to anthrax spores (Infect. Immun. 2005, 73, 795). That means it can be used either as a prophylactic or as an antidote. "What's really neat," Iverson pointed out, "is that the animals survived without antibiotics. I assumed that antibiotics would be needed to keep the animals from dying. This is not the case. The antibody itself is enough for the animals to survive."

The Iverson-Georgiou lab, meanwhile, has created a next-generation antibody with an even higher affinity to protective antigen. "We wondered whether we could--instead of making an entire IgG, which is complicated and expensive to make--just take the binding site, make it in bacteria, add a PEG [polyethylene glycol] chain, and still get therapeutic benefit," Iverson told C&EN. If so, "we can think about production in bacteria as opposed to more expensive mammalian cell culture."

Preliminary work shows that the approach is "at least promising," Iverson said. Of the guinea pigs treated at SFBR with the antibody fragment and then exposed to anthrax spores, 60% survived. How well the antibody fragment compares with the full antibody is not yet clear. Iverson and SFBR are just launching a head-to-head comparative study.

In the meantime, Iverson has become intrigued. In the surviving animals given the prophylactic treatment, the spores never gave rise to bacterial infection. Could it be, Iverson wondered, that some part of the process by which anthrax spores turn to bacteria involves the binding of protective antigen to its receptors?