Evaluating the Effectiveness of Injectable and Oral Vaccines for Johne’s Disease in Cattle

Background

Johne’s disease results in thin, water “firehose” diarrhea, extreme weight loss and early culling (or death) in mature cattle. It is caused by a bacterium called Mycobacterium avium subspecies paratuberculosis (MAP). The disease starts when young calves consume infected milk or manure from their dam’s udder or elsewhere in the environment. The MAP bacteria then enter the animal’s intestinal cells and hides from the immune system for months or years. As the bacteria build up they cause significant damage to the intestine and reduce the intestine’s ability to absorb nutrients. MAP can also leave the intestinal cells, re-enter the gut and get shed into the environment to infect new animals. MAP shedding usually starts long before clinical signs of Johne’s disease appear, making the disease very difficult to manage. Current diagnostic tests have low sensitivity (particularly in the early stages of disease), so a lot of infected cattle aren’t detected. Some Johne’s disease vaccines have been developed but are not available in Canada. Current vaccines can reduce shedding but don’t prevent infection, and they can also produce false positives for bovine tuberculosis. Because infected cows often shed more MAP at calving, there’s a good chance that calves will be exposed to MAP before they can be vaccinated. These researchers are working on better vaccination strategies to prevent Johne’s disease.

Objectives

• Determine if an injectable (parenteral) MAP vaccine provides sustained control of MAP infection in the mid-jejunum and terminal small intestine,
• Determine if an oral (enteric) vaccine can control MAP infection throughout the entire small intestine,
• Determine if a vaccine administered following MAP infection of young calves can control MAP burden and shedding in the small intestine, and
• Identify specific MAP vaccine proteins contributing to control of MAP infection.

What They Will Do

The initial MAP infection appears to occur at two different sites in the small intestine, and it causes a different immune response at each site. This team has developed a surgical technique to create stand-alone “loops” of intestine that are connected to the rest of the intestine by the bloodstream, but digesta doesn’t enter or flow through them. This allows the team to study how the different parts of the intestine respond to the same challenge (like MAP infection or vaccination).

This team will use this loop model to study the effectiveness of an existing (Australian) vaccine against MAP infection at both sites, and to determine whether a strain of MAP that does not cause Johne’s disease can be used as an oral vaccine. MAP shedding and various immune responses will be measured in each study. They will also determine whether vaccination after MAP infection can still provide some protection against Johne’s disease. They will screen a collection of MAP proteins identified in earlier studies to see whether any of them provoke the same immune response as an actual MAP bacterial infection. If so, these proteins could form the basis of a future MAP subunit vaccine that doesn’t cross-react with bovine tuberculosis tests.

Implications

Johne’s disease is relatively uncommon among Canadian beef cows, but it can be very costly when it does occur. An effective vaccine to prevent it would be valuable.