Double Shot: Anthrax vaccine gets makeover

Anthrax, a scourge once confined to farmers and wool handlers, has become a member of the rogues’ gallery of biological weapons. Although there’s a vaccine against anthrax, it’s been the target of such strong criticism that a government-funded panel last year recommended that researchers find an alternative.

Scientists now report that in mice, a dual-purpose experimental vaccine appears to spur the immune system to disable anthrax’s lethal toxin at the same time it kills the bacterium. The current vaccine targets only the toxin.

Meanwhile, another group presents new findings about how anthrax toxin kills.

Researchers at Harvard Medical School in Boston gave mice three injections of either the vaccine or an inert substance over 4 weeks. Two weeks after the last shot, the animals received an injection of anthrax toxin. All vaccinated mice survived, having formed antibodies that recognized and disabled the toxin. The other mice all died within a day of receiving the toxin.

In another part of the experiment, the researchers drew blood from vaccinated mice and exposed it to the bacterium Bacillus licheniformis as a stand-in for the more dangerous Bacillus anthracis, which causes anthrax. The vaccinated mice made antibodies that surrounded and killed B. licheniformis, suggesting that the new vaccine would do the same to B. anthracis, says study coauthor Julia Y. Wang. The findings appear in the September 16 issue of the Proceedings of the National Academy of Sciences.

“It’s a double whammy,” says Vincent A. Fischetti of Rockefeller University in New York. The new vaccine will include material from the capsule that normally shields B. anthracis from the immune system. To make the two-part experimental vaccine, Wang and her colleagues chemically attached B. licheniformis capsule material to a portion of the B. anthracis toxin. The combination made the bacterium “visible” to the mouse immune system, Wang says.

This same strategy works in a pneumonia vaccine already in use, Fischetti says.

The current anthrax vaccine requires six shots over 18 months. The panel of the Institute of Medicine (IOM) in Washington, D.C., last year cited this regimen as a major drawback. The new dual-action vaccine could require half as many shots, Wang says.

However, the new vaccine would contain the same antitoxin ingredient that constitutes the existing vaccine. So it’s unclear whether it would avoid the fatigue, memory loss, malaise, and other symptoms reported by some of the roughly 2 million military and other personnel who have received the current anthrax inoculations.

The IOM panel found no more adverse effects with the existing vaccine than with several of those for other diseases.

Even as Wang and her colleagues strive to develop a better anthrax vaccine, other scientists are still trying to decipher the details of how the microbe’s toxin kills. New findings indicate that the toxin causes harm distinctive from that of other bacteria. It triggers “a unique kind of shock,” says Stephen H. Leppla of the National Institute of Allergy and Infectious Diseases in Bethesda, Md.

Researchers have known that anthrax toxin damages blood vessels, resulting in internal bleeding and a buildup of fluid around the lungs that impedes breathing. One school of thought holds that the toxin attacks immune cells called macrophages and that this assault unleashes inflammatory proteins that damage the blood vessels. Leppla and his colleagues observed hundreds of mice reacting to anthrax toxin. In the September Journal of Clinical Investigation, the researchers report that two primary suspects among the inflammatory proteins don’t seem to play a large role in the disease.

However, the team found that the animals’ tissues become starved of oxygen. Damage was greatest to the liver, spleen, and bone marrow, says Leppla. Liver damage can release chemicals that do wide-ranging harm. “I’d like to know the molecular events causing liver cells to die,” Leppla says. The new findings might spur research into the toxin’s effect on liver cells, he adds.

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