Disarming Anthrax

High-affinity antibodies to a component of anthrax toxin protect laboratory animals exposed to anthrax spores without help from antibiotics, according to chemistry professor Brent L. Iverson of the University of Texas, Austin. He spoke at a symposium organized by the Division of Organic Chemistry at this week’s American Chemical Society national meeting in Washington, D.C.

Antibiotics currently 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 too late.

Iverson develops technologies to make better antibodies through a lab he jointly runs with colleague George Georgiou. In the late 1990s, that lab engineered an antibody for the anthrax toxin component known as protective antigen. Its efficacy is based on selective and high-affinity binding to protective antigen, which prevents it from reaching its receptor. After showing promising results in studies at the Southwest Foundation for Biomedical Research (SFBR), San Antonio, the antibody was licensed by Elusys Therapeutics, which turned it into a full immunoglobulin G (IgG), Iverson said.

Elusys recently has shown that the antibody protects rabbits before and after exposure to anthrax spores, Iverson said. That means it can be used either as a prophylactic or as an antidote. “What’s really neat,” Iverson told C&EN, “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 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” required to make the full IgG.

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.