Italians discover mouse model for ulcers.
The corkscrew-shaped bacterium in question--Helicobacter pylori- - infects an estimated 50 percent of the world's population.
Researchers had previously infected monkeys and pigs with H. pylori, enabling scientists to study the disease. But these animals are large, expensive, and sometimes hard to handle. Now Rino Rappuoli of the Immunobiological Research Institute of Siena in Italy and his colleagues have created a cheap, easy-to-use rodent model of ulcers.
The Italian team first infected mice with a strain of H. pylori known as type I. Those mice soon resembled their suffering human counterparts, exhibiting ulcers and severe stomach inflammation.
"The beauty of this model is that we reproduce the full-blown disease," Rappuoli says. This finding fits with the observation that type I H. pylori predominates among humans with ulcers.
The team also reports that mice infected with the type II strain of H. pylori showed signs of mild gastric inflammation but did not develop ulcers.
The researchers then turned their attention to the development of a vaccine. They knew that type I H. pylori produces a protein called vacuolating cytotoxin (VacA) that, with long-term exposure, ulcerates the lining of the stomach. Could they harness this powerful protein to provoke an immune response that would shield uninfected mice from H. pylori infection?
Rappuoli's team gave healthy mice two doses of VacA in solution 14 days apart and then challenged them with type I bacteria. The researchers found no evidence of H. pylori infection or ulcers in the mice.
To see if they could ward off type II infection in the animals, the researchers turned to another protein--urease--that is produced by both strains of H. pylori. They discovered that a solution of urease generated a response that protected mice from infection with either type I or type II H. pylori.
All told, the team has conducted 13 separate experiments with more than 300 mice. In the March 17 Science, they report that 79 percent of vaccinated mice resisted H. pylori infection.
The findings raise the prospect of developing a vaccine that could be given to human infants to ward off H. pylori infection, remarks infectious disease specialist Lucy S. Tompkins of the Stanford University School of Medicine, who wrote an accompanying comment in Science.
She believes researchers can use this mouse model to delve into the mystery of how H. pylori evades the human immune system to cause a lifelong infection. "The development of a small rodent model--where you could examine how the organism causes the disease- -is critically important," she adds.
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|Title Annotation:||study of Helicobacter pylori in mice could lead to vaccine for humans|
|Article Type:||Brief Article|
|Date:||Mar 18, 1995|
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