Science Moving Closer to Plague Vaccine

New approach works in mice, but effectiveness in humans unknown

Randy Dotinga

Randy Dotinga

Published on May 17, 2005

TUESDAY, May 17, 2005 (HealthDay News) -- American scientists say they've taken a step toward developing a vaccine against the plague, an ancient disease that could pose a new threat in the age of bioterrorism.

The researchers say an experimental vaccine appears to protect mice against the inhaled form of the plague -- caused by the bacterium Yersinia pestis -- raising hopes it might also work in humans.

While specialists don't consider the disease to be as big of a terror threat as anthrax or smallpox, study co-author Steven Mizel said it shouldn't be ignored.

"Given the fact that it knocked off approximately 25 percent of the European population in the Middle Ages, it has a pretty good track record as a pathogen," said Mizel, chairman of the Department of Microbiology and Immunology at Wake Forest University Baptist School of Medicine, in Winston-Salem, N.C.

The goal of vaccines is to prime the immune system so the body flies into action immediately -- and knows exactly what to do -- when it encounters a specific germ. Scientists use a weakened form of the germ to trigger an immune system reaction that stops short of making the vaccine recipient ill.

Ideally, this process 'primes' the immune system to recognize and attack the full-strength germ, should it encounter it later on.

But this weakened-germ approach has its flaws. "In many cases, it doesn't work very well, or it works too well and makes people very sick," especially those with AIDS or other immune disorders, Mizel explained.

In his current research, Mizel and a colleague developed a vaccine by crossing a weakened form of the plague germ with a protein that produces flagellin -- tiny whip-like arms that allow the bacteria to paddle around.

Mizel was scheduled to report his findings Tuesday at the Digestive Diseases Week 2005 meeting, in Chicago.

Hundreds of mice given the vaccine through nose droplets remained healthy when exposed to the plague virus with flagellin, the researchers report. In contrast, those vaccinated with the flagellin-free form of the vaccine got sick and died.

"It turns out that the main protein of that flagellin is extraordinarily potent in activating the immune system," Mizel explained.

The vaccine only protects against the pneumonic [respiratory] form of plague, which is transmitted through the air. Another form, called bubonic plague, is usually transmitted through fleas and was a major source of infection in centuries past. Bubonic plague is not considered a major terrorism threat today, however.

Because of ethical constraints, it will be impossible to test the vaccine in humans. "Obviously, we're not going to stick plague bacteria into people," Mizel said.

But current tests in monkeys should give researchers a good idea of whether or not the vaccine works in humans, he said. So far, researchers haven't noticed any side effects in animal studies.

If the vaccine is a success, it might be used to protect medical teams, rescue workers and other people who would be 'first responders' to a bioterrorism attack, Mizel said.

Not everyone thinks the new research really a huge step forward, however.

"It looks like incremental progress, and it's also a little bit of biodefense project hype," said Dr. Donald Mosier, a professor of immunology at The Scripps Research Institute in La Jolla, Calif. "It's a nice finding, but not the kind of advance that I think warrants a big press release or national news attention."

Also, he said, there's no guarantee that a vaccine that works in mice will also work in humans. "As we learned in the AIDS vaccine field, it's difficult to translate what you find in a mouse up to primates, and then make the smaller jump from primates to humans," he said.

More information:

Learn more about pneumonic plague from the U.S. Centers for Disease Control & Prevention.

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