Is There a New Johne’s Disease Vaccine on the Horizon?

Background

Vaccines are among the most important tools for controlling infectious diseases in cattle. Most available vaccines are effective at generating an antibody response. Antibodies recognize and bind to disease-causing pathogens. This attracts the host’s immune cells to attack the pathogens. But some pathogens can enter host cells and hide from the immune system, so vaccines that generate an antibody response don’t provide much protection against them (such as those that cause Johne’s disease, tuberculosis and many viral diseases). Therefore, a vaccine must also trigger cell-mediated immunity to combat intracellular pathogens.

Mycobacterium avium subspecies paratuberculosis (MAP) causes Johne’s disease. Although Johne’s is more common in dairy herds, a study estimated that 24% of western beef herds are affected (Johnson et al., 2022). MAP infects gut cells, causing them to burst, spread and infect other herd mates, mainly through feces. Clinical signs (e.g., weight loss, diarrhea, loss of body condition) are usually not evident until adulthood (cows 4-7+ years of age). This means Johne’s usually has been spreading for a long time before it is detected in the herd. There is no effective treatment for affected animals, nor are there any vaccines approved for use in Canada. Bacterin-based vaccines are used in Spain and Australia against Johne’s disease. These can reduce shedding of MAP but do not prevent infection and can cause a “false positive” diagnosis for tuberculosis. In Canada, Johne’s control programs rely on fecal testing to detect shedding, blood testing to assess exposure via antibodies and culling of positive animals.

Developing an effective vaccine against Johne’s disease for use in Canadian herds is an important step toward reducing the spread of the disease. However, current technologies used for vaccine development require extensive testing of each specific pathogen the vaccine is intended to target. This means it takes significant effort and money to bring new vaccines to market using current vaccine technologies. Given this, a plug-and-play vaccine platform that uses a standardized, validated, reusable backbone adaptable to different pathogens to stimulate T cell-mediated immunity would be ideal. If successful, this same backbone could also be used to develop vaccines for other infectious diseases such as respiratory disease and scours.

Objectives

1. Generate a prototype Mycobacterium smegmatis (Msm) vaccine for Johne’s disease.
2. Assess the immune response induced by this vaccine when calves are injected.
3. Assess the immune response induced by this vaccine when given orally to calves.

What They Will Do

This team wants to determine whether Msm (a harmless intracellular bacterium related to the bacteria that cause tuberculosis and Johne’s disease) can serve as a new vaccine delivery vector to stimulate cell-mediated immunity.

In a previous project, this research team demonstrated that these bacteria can be used to “dress up” to resemble tuberculosis antigens, protect mice from tuberculosis and not cause disease or interfere with its diagnosis (differentiating infected from vaccinated animals, or DIVA). However, this vaccine has not been assessed in cattle.

In Year 1, they will confirm that Msm vaccine strains can express MAP proteins within bovine immune cells, demonstrate that these proteins are effectively processed and presented to the immune system and establish that the Msm backbone functions as a natural adjuvant that activates bovine macrophages and dendritic cells to stimulate T cell-mediated immunity.

In Years 2 and 3, one-month-old calves from a Johne’s-free dairy herd (three per group) will be subcutaneously inoculated with three different doses of the Msm vaccine strain (plus an unvaccinated control). Monthly blood samples will confirm that the calves were free of maternal antibodies against Johne’s disesase to begin with, then assess antibody and cell-mediated immunity. The BOVIGAM™ TB test will be performed on all calves to ensure the vaccine does not cause a cross-reaction.

In Years 2 and 3, they will use the gut loop model they developed to assess whether oral delivery of the vaccine elicits an immune response in calves’ digestive systems.

Implications

If this new vaccine delivery method works, it will be the first DIVA vaccine developed against Johne’s disease. Also, its backbone may be used to develop other vaccines against intracellular pathogens, such as those causing scours and respiratory disease.