Researchers at New York University ( NYU ) School of Medicine created the first active vaccine that can significantly delay and possibly prevent the onset of a brain disease in mice that is similar to mad cow disease.

The new findings could have implications for the development of a vaccine to prevent some fatal brain diseases caused by unusual infectious particles called prions.

The NYU study, led by Thomas Wisniewski, has showed that active immunization can protect a significant percentage of animals from developing symptoms of prion disease.

The prion vaccine developed at NYU would most likely first be used to protect livestock, since most prion infections occur in animals and are thought to be transmitted orally.

The version of prion disease that affects humans usually occurs spontaneously, and only rarely as a result of eating contaminated meat.

The NYU study is also the first to use a mucosal prion vaccine, given by mouth rather than through the skin, which localizes the initial immune response to the gut and mainly stimulates an antibody response, says Wisniewski. " By giving our vaccine orally, we're stimulating an immune response mainly in the digestive tract," he explains. " Thus, harmful prions in contaminated food will be destroyed in the gut and will not reach other organs in the body. "

Because the research was conducted in normal mice, the NYU researchers say it will be easier to apply in animals in the wild, which are at risk for developing prion disease.

Prion disease is contracted when an animal eats the body parts of other animals contaminated with prions. What makes these infectious particles unusual is that they are proteins that have the same amino acid composition as equivalent proteins occurring naturally in the body. But the prions turn deadly by changing shape.
These " misfolded " proteins tend to aggregate in toxic, cell-killing clumps. As an infection takes hold, prion proteins invade brain tissue and force normal proteins to adopt their configuration. In time, the diseased animal develops dementia, loses control of its limbs, and eventually dies.

There are no treatments for prion-related diseases, and prions can easily infect the body because they do not elicit any immune response.

To create a vaccine that could rally the immune system of mice, the NYU researchers designed a vaccine in which scrapie prions were attached to a genetically modified strain of Salmonella.
This bacterium is also used in several animal vaccines and in human vaccines for cholera and typhoid fever.

Among mice vaccinated prior to prion exposure, approximately 30% remained alive and symptom-free for 500 days, according to the study.
By comparison, mice that didn't receive the vaccine survived only an average of 185 days, and all were dead by 300 days.

The NYU scientists are in the process of redesigning the vaccine for deer and cattle.
After choosing the appropriate bacteria for each vaccine, they must genetically modify it to carry the prion protein.

Source: Neuroscience, 2005


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