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Biological Chemistry

Antibody Could Lead To Anthrax Test

Antibody-based technique might provide advantages over PCR procedure

by Stu Borman
August 23, 2006 | A version of this story appeared in Volume 84, Issue 35

MODEL
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Credit: SWISS FEDERAL INSTITUTE OF TECHNOLOGY
Seeberger (left) and postdoctoral fellow Daniel B. Werz hold a molecular model of the anthrax surface tetrasaccharide analog they used to elicit antibodies for potential use in an anthrax confirmatory assay.
Credit: SWISS FEDERAL INSTITUTE OF TECHNOLOGY
Seeberger (left) and postdoctoral fellow Daniel B. Werz hold a molecular model of the anthrax surface tetrasaccharide analog they used to elicit antibodies for potential use in an anthrax confirmatory assay.

A Swiss group has developed a monoclonal antibody (mAb) that could provide the basis for a confirmatory test to determine if a patient is infected with Bacillus anthracis, the microorganism that causes deadly anthrax.

UNIQUE
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Seeberger and coworkers synthesized an analog (R = 4-pentenyl) of Bacillus anthracis's surface tetrasaccharide (R = H) and linked it to a protein carrier to elicit a specific mAb that can potentially be used to diagnose anthrax infection.
Seeberger and coworkers synthesized an analog (R = 4-pentenyl) of Bacillus anthracis's surface tetrasaccharide (R = H) and linked it to a protein carrier to elicit a specific mAb that can potentially be used to diagnose anthrax infection.

Anthrax has already been used as a bioterrorism agent. Once people inhale anthrax spores, the resulting infection generally kills them quickly if untreated, so improved techniques to diagnose the condition are always in demand. A number of rapid, inexpensive tests are available to screen patients for anthrax, but the polymerase chain reaction (PCR) procedure often used to confirm positive screening results is difficult to carry out.

Professor of organic chemistry Peter H. Seeberger of the Swiss Federal Institute of Technology, Zurich, and coworkers have now devised a mAb specific for B. anthracis. A test based on the mAb could provide advantages over PCR for such confirmations (Angew. Chem. Int. Ed., DOI: 10.1002/anie.200602048).

The mAb they developed recognizes and binds to a key tetrasaccharide on the anthrax spore's surface, one sugar of which is a recently discovered monosaccharide named anthrose. Seeberger and coworkers synthesized the unique tetrasaccharide for the first time last year (Angew. Chem. Int. Ed. 2006, 44, 6315). They used this synthetic procedure to create a close analog of the tetrasaccharide, conjugated it to a protein to make it immunogenic, and used the construct to elicit a mAb that recognizes the tetrasaccharide specifically. This mAb can now potentially be used in a convenient antibody-based assay that the researchers believe will confirm the presence of anthrax with a high level of confidence.

"Our results demonstrate that small differences in the carbohydrates on cell surfaces can be used to obtain specific immune reagents," Seeberger says. "Our new antibodies will be used as the basis for highly sensitive anthrax diagnosis and will contribute to the development of new therapeutic approaches." Seeberger believes that the mAb-based method will be faster and more convenient than PCR and notes that he and his coworkers are also currently further developing the mAb as an antianthrax vaccine candidate.

Asked to comment on the work, chemistry professor Samuel J. Danishefsky of Memorial Sloan-Kettering Cancer Center and Columbia University, New York City, who specializes in carbohydrate chemistry, says, "The Seeberger paper is a beautiful illustration of how sophisticated chemical synthesis can be interfaced with the power of immunology to address urgent public needs."

Chemistry professor Timothy M. Swager of Massachusetts Institute of Technology, whose research focuses on molecule-based sensors, says, "The work does have good prospects for impact, and the authors are correct" that the mAb-based technique could offer speed and ease-of-use improvements over PCR. "In the sensitivity category, you can't presently beat PCR," Swager notes. Nevertheless, because of greater possibilities for operator error with a trickier test like PCR, "I would expect that an easier antibody assay may be more reliable," he says.

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