Scientists have developed an unusual vaccine that prevents some strokes in laboratory rats. The treatment works by desensitizing the animals' immune system to a protein residing within their blood vessels.
When displayed on a blood vessel's lining, the protein, called E-Selectin, facilitates the binding of white blood cells to the vessel wall and elicits an inflammatory reaction that can lead to a stroke. By continually exposing rats to human E-Selectin using a nasal spray, researchers short-circuited that inflammatory process.
The researchers tested the nasal vaccine in rats bred to have high blood pressure and hence an elevated risk of stroke. Rats receiving repeated doses of the nasal spray over their lifetime remained significantly less susceptible to stroke than were rats getting sprays containing saline mist or an innocuous chicken protein.
There are two recognized types of stroke. Rats receiving the placebos averaged more than three hemorrhagic strokes in their lifetime, while those getting E-Selectin had none. Rats getting the saline or chicken protein sprays also averaged 16 times as many blockage-type strokes as E-Selectin–treated rats did, the researchers report.
Their findings appear in the September Stroke.
The vaccine differs from traditional immunizations, which prime the immune system to attack invaders. "This is not an active immune response, it's a suppression," says coauthor John Hallenbeck, a neurologist at the National Institute of Neurological Disorders and Stroke in Bethesda, Md.
Hallenbeck suspects that nasal delivery is integral to the process. The body encounters myriad foreign bodies via the mucus lining of air passages. Because such exposure is so frequent, he says, the overwhelming tendency is for the immune response to tolerate rather than attack compounds introduced nasally.
E-Selectin provided in a nasal spray may even encourage the production of specialized immune cells–known as regulatory T cells–that make anti-inflammatory proteins, Hallenbeck says. Indeed, spleen samples from rats given a blood-vessel irritant show increased production of an anti-inflammatory protein known as transforming growth factor–beta in the animals treated with E-Selectin, compared with other animals.
"This is an interesting phenomenon and a potential clinical application of regulatory T cells," says immunologist and vascular biologist Jordan S. Pober of Yale University.
However, he says, the researchers still need to determine whether the vaccine actually leads to the production of regulatory T cells and whether a version of the protein from another species is required to get the effect.
"The development of regulatory T cells in general–by oral or mucosal tolerance–is mysterious" and currently a hot topic of study, Pober says.
Hemorrhagic and blockage-type strokes often result from atherosclerosis, a condition in which fatty plaques accumulate in the arteries. But such strokes have also been linked to high blood pressure, as in the rats, apparently when damage to the vessel walls causes E-Selectin release, which then begets inflammation, Hallenbeck says.
The researchers plan next to test the vaccine on people.
National Institute of Neurological Disorders and Stroke
National Institutes of Health
36 Convent Drive
Bethesda, MD 20892-4128
Jordan S. Pober
Section of Immunobiology
Yale University School of Medicine
330 Cedar Street
P.O. Box 208011
New Haven, CT 06520
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