Active Vaccine Prevents Mice From Developing Prion Disease

NYU School of Medicine scientists have 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, published online this week in the journal Neuroscience, could provide a platform for the development of a vaccine to prevent a group of fatal brain diseases caused by unusual infectious particles called prions.

Although no cure for these diseases -- which include scrapie, mad cow disease, and chronic wasting disease -- is on the horizon, many research groups in both the United States and Europe are working on prion vaccines. But the NYU study is important because it breaks new ground in demonstrating that active immunization can protect a significant percentage of animals from developing symptoms of prion disease, explains Thomas Wisniewski, M.D., Professor of Neurology, Pathology, and Psychiatry, and the lead author of the study.

The vaccines that provide active immunization are made, in part, from proteins found on disease-causing organisms. In response to these proteins, the animal's immune system produces antibodies that will destroy them any time they appear in the body. Most vaccines in use today provide such active immunization.

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

"The potential use for a prion vaccine in humans is still theoretical," says Dr. Wisniewski. "But if, for example, there is ever a more significant outbreak of chronic wasting disease and if this disease were found to be transmissible to humans, then we would need a vaccine like this to protect people in hunting areas."

Currently, an outbreak of chronic wasting disease is occurring in some Western states, and the disease's geographic range is expanding. Two cases in wild deer have recently been reported for the first time in New York State, according to the New York State Department of Environmental Conservation.

First mucosal prion vaccine

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 Dr. 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. "These technical issues are not major hurdles," says Dr. Wisniewski. "Developing a marketable vaccine for livestock is something that is very achievable."

The authors of the new study are: Fernando Goñi, Elin Knudsen, Henrieta Scholtzova, Joanna Pankiewicz, Einar M. Sigurdsson, and Thomas Wisniewski of the NYU School of Medicine; Fernanda Schreiber and Jose Alejandro Chabalgoity of the University of Uruguay; Richard Carp and Harry C. Meeker of the New York State Institute for Basic Research in Developmental Disabilities, New York City; David R. Brown of the University of Bath, United Kingdom; and Man-Sun Sy of Case Western Reserve University School of Medicine, Cleveland, Ohio.

Source : NYU Medical Center