CWD vaccine delays illness in mice

Several vaccine candidates could prolong lives of animals infected with chronic wasting disease and reduce spread of the disease.

Researchers from the University of Calgary Faculty of Veterinary Medicine indicate four vaccine candidates prolonged the lives of healthy mice that had been modified to produce an elk-type prion protein when infected with CWD prions. Dr. Hermann Schaetzl, an associate dean and leader of the Calgary Prion Research Unit, said he expects the vaccines produced by his research team will reduce infection rates and shedding.

The Journal of Biological Chemistry published the study results Dec. 21 in the article "Recombinant prion protein vaccination of transgenic elk PrP mice and reindeer overcomes self-tolerance and protects mice against chronic wasting disease."

CWD is an always-fatal neurologic disease that has spread among captive and wild cervids in 26 U.S. states, three Canadian provinces, Finland, Norway, South Korea, and Sweden, according to the U.S. Geological Survey National Wildlife Health Center. The disease spreads through misfolded prion proteins shed in saliva and waste, and they may remain viable in environments for years or decades.

Dr. Schaetzl said a prophylactic vaccine needs to overcome an immune system's blindness against prion infections. After initial infection, the disease spreads through misfolded proteins from an animal's own body.

"Our vaccine is actually against the normal form of the prion protein, and our antibodies should bind to the normal prion protein," he said. "And by binding to the normal prion protein, they basically block the replication in case the bad and infectious form of the prion protein comes in."

The researchers administered the mice one of four vaccines that contained noninfectious recombinant prion proteins over several weeks before challenging them with disease-causing prions.

Control mice became sick in about 110 days, but vaccinated mice stayed healthier longer, Dr. Schaetzl said. One vaccine candidate gave mice about 70 more days until clinical signs, he said.

Dr. Schaetzl expects, but has not yet confirmed through studies, that the vaccines would reduce the rate of infection among animals exposed to infectious prion proteins. He also expects they will reduce shedding of CWD prions among infected animals by reducing the presence of those prions outside of the brain, but that also needs further study.

Dr. Schaetzl's team is planning further studies on the vaccines' effects on cervids, as well as efforts to transition from injectable to oral vaccination, which may include delivery through plants that can be fed at wildlife gathering points.

The folds in disease-causing prion proteins can change through mutation and selection, causing different shapes that Dr. Schaetzl likened to strains of a virus. He said the vaccine candidates studied in the Calgary laboratory also can be modified in two areas to protect against multiple strains.

"We work with certain strains here—certain CWD strains—and there's a variety out in the field that is slightly different," he said.

CWD may have zoonotic potential despite what seems to be a high species barrier, Dr. Schaetzl said. The more disease-causing prion proteins in cervids, the more chances some will mutate into forms that could jump that barrier, he said.

"A vaccine really would make sense to contain, at the long term, this disease, even if the vaccine is not perfect," he said. "If you have a vaccine which is only 30%, 50%, 60% effective, it still would add up over time."

Related JAVMA content:

As CWD spreads in cervids, states also monitor humans (Sept. 15, 2018)

Chronic wasting disease continues to spread (Aug. 15, 2017)