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Developing a vaccine to combat Johne’s disease

Canadian researchers are trialling vaccine candidates, and plan to have results in the fall

Just as researchers around the world are racing to find a vaccine for the COVID-19 virus, Canadian scientists have been diligently working to discover a vaccine that works on Johne’s disease in cattle.

“We have successfully established and validated our research model using a commercial MAP vaccine currently licensed for use in Australia and Spain,” says Dr. Philip Griebel, who specializes in neonatal immunity at the Vaccine and Infectious Disease Organization — International Vaccine Centre (VIDO-Intervac) in Saskatoon, Sask.

The VIDO-Intervac MAP team (l. to r.): Alain Fafard, Stew Walker (behind), Neil Rawlyk (front), Philip Griebel (back) Antonio Facciuolo (front), Scott Napper (back), Hugh Townsend (intermediate), Elodie Pastural (front), and Volker Gerdts (end).photo: Supplied

Griebel also holds the Canada research chair in neonatal mucosal immunology and is a professor at the School of Public Health at the University of Saskatchewan. He’s working with Dr. Antonio Facciuolo, a post-doctoral fellow in microbiology and immunology at VIDO-Intervac. The University of British Columbia is also involved in the project.

MAP is Mycobacterium avium subspecies paratuberculosis, and it’s the bacter­ium that’s responsible for Johne’s disease, a chronic and often fatal infection usually found in the small intestine of ruminants.

The disease is contagious and infected cows can shed the bacteria in their feces and milk. Young calves that ingest the colo­strum or milk are at an especially high risk of acquiring the infection. The bacteria can also be present on the cow’s udder, in the pen and in the water supply. This is known in both animals and humans as fecal-oral transmission.

It’s tricky to diagnose, because while the symptoms include weight loss and lower milk production, there’s no fever or loss of appetite. Many cattle go undiagnosed and the disease isn’t discovered until a large number of the herd is infected.

As a result, the Johne’s Disease Information Center at the University of Wisconsin – Madison says, “over 50 per cent of dairy herds in most major dairy producing countries are now MAP-infected. The official estimate in the U.S. from a survey conducted in 2007 and published in 2013 is that 91 per cent of U.S. dairy herds are infected. This is up from USDA’s 1996 estimate that 21.6 per cent of U.S. dairy herds have paratuberculosis.”

The disease — whose name derives from the German pathology professor who discovered it in the late 19th century — has spread from dairy to beef cattle, sheep, goats, bison, deer, elk and many other exotics in zoos.

The new research model that Dr. Griebel and his team have developed took about seven years to come to fruition. It enables the scientists to replicate MAP infection at specific sites in the small intestine of young calves. Over that same period, progress in recombinant DNA technology and computer-based prediction programs has allowed the researchers to predict and produce many vaccine candidates.

“We have produced 96 vaccine candidates that are ready to test,” Dr. Griebel says, adding that they’re working on vaccine formulation strategies to make sure the candidates are stimulating the immune response in the young calves.

The University of British Columbia’s job has been to use various computer-algorithm-based ways to predict new vaccine candidates, then produce and purify the proteins in their lab. VIDO-Intervac tests the candidates in young calves using the research model, and then tests the actual vaccines in animals.

They also determine whether the vaccine reduced the amount of bacterial infection compared to unvaccinated animals, what kind of immune response was produced, whether that response can be used to more quickly screen other candidates and whether there are adverse reactions to the vaccine.

“As importantly, we also ensure the vaccine candidate does not cause a positive reaction with the bovine tuberculosis test,” Dr. Griebel says, adding that all these steps are necessary to make sure the vaccines actually prevent or control the infection and are safe to use in Canadian cattle.

Work at VIDO-Intervac began in 2016 through the federal agency Genome Canada and its subsidiaries Genome B.C. and Genome Prairies. Prior to that, research projects were funded by the Beef Cattle Research Council and the Saskatchewan Agricultural Development Fund.

Currently, no Johne’s disease vaccines are licensed in Canada and the ones that are commercially available in places like the U.S., Spain and Australia are not effective, or interfere with bovine TB testing. So far, the only way to reduce the prevalence of the bacteria is to test and cull infected animals and maintain good hygienic practices on the farm. These aren’t very effective either.“Today’s diagnostic tests lack sensitivity — the ability to identify all infected animals — which translates to a number of animals going undetected and remaining in the herd,” Dr. Griebel says, adding that even with hygienic farm management practices, tests need to be conducted regularly to find infected animals.

A safe and effective vaccine would stimulate the immune response in calves and cows, thereby preventing or controlling infection and MAP shedding in feces. Transmission would go down and, over the long term, the bacteria could be eliminated in the herd.

Dr. Griebel says that a vaccine trial to analyze the duration of immune protection in the vaccine screening model is in progress but results won’t be available until this fall.

He warns that even the best vaccine is still no silver bullet.

“We want to emphasize that control of Johne’s disease cannot be achieved by a single strategy such as vaccination,” he says. “An integrated management approach that involves test-and-cull of infected animals and control of bacterial contamination in the environment must be instituted along with vaccination to eliminate the threat of the disease.”

Source: Canadian Cattleman


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