Vaccine candidate? Researchers synthesize oligosaccharide from anthrax pathogen

For weeks a white powder caused fear and shock for the American population: a few days after the attacks on September 11th, 2001, four innocent people became the victims of letters that contained the powder - spores of the anthrax pathogen. German researchers have now synthesized a molecule characteristic of anthrax in the laboratory which may be the basis for a new anthrax vaccine.

Spores from Bacillus anthracis cause a disease called anthrax which affects herbivores such as cattle, sheep, and goats. Humans are only rarely infected. However, it is possible to specially prepare the extremely hardy spores for use as a biological weapon. Those who inhale these spores normally die within a few days. To prepare for this threat, effective vaccines are required.

The first step in the development of a vaccine is the search for a suitable antigen. An antigen is a molecule or part of a molecule from a pathogen to which the immune system reacts by forming antibodies. This antigen cannot be a “run-of-the-mill” molecule; it must be characteristic for the specific disease. As in most bacteria, Bacillus anthracis has specific oligosaccharides on the surface of its spores which probably play an important role in the interaction between the bacteria and the infected organism. The structure of such an oligosaccharide was determined last year. The molecule consists of four sugar units. Of particular interest is one of the terminal sugar units, called anthrose, which clearly appears exclusively on the surface of anthrax spores.

Peter Seeberger and Daniel Werz at the ETH in Zurich have now generated this tetrasaccharide by a total synthesis for the first time. At the core of their method is a new, particularly effective synthetic pathway for the anthrose unit. At the same time, the researchers also attached a type of molecular hook to the synthetic molecule. The hook can subsequently be coupled to a transport protein, which is necessary for successful immunization. The overall synthetic pathway is so flexible that different variations of the sugar molecule are easily accessible. “We are currently carrying out immunological studies with the tetrasaccharide,” says Seeberger, “at the same time, we are preparing a number of derivatives of the sugar in order to highlight their potential as highly specific anthrax vaccines.”