A Better Vaccine for Bovine TB

Background

Bovine tuberculosis (bTB) is a deadly and reportable disease that not only affects cattle, but a wide array of livestock and wildlife species and can be transmitted within and between these populations. While bTB outbreaks are typically rare, we are still seeing cases across Canada most recently in July of 2023. While there is a vaccine available that is commonly used in humans and for certain wildlife, it is not permitted in Canada due to causing false positives in current testing methods. As of today, testing and culling infected herds is the only way to deal with the disease. This approach has costed the industry and federal government millions of dollars, provides no protection to Canadian cattle herds, and threatens Canada’s bTB-free status which could jeopardize our ability to trade internationally. The MSX-1 vaccine, however, could be an effective alternative. While the currently used vaccine uses BCG, MSX-1 uses Mycobacterium smegmatis which would mean providing protection without impacting the ability to test for bTB infection.

Objectives

• Evaluate if the MSX-1 live vaccine effectively prevents bovine tuberculosis (bTB) infection without interfering with tuberculin, which is currently used to diagnose bTB, using mice as a model.

What they will do

This team will conduct two trials using mice to prove the MSX-1 is a good candidate to prevent bTB infection in Canadian Cattle herds. For each trial, mice will be vaccinated with MSX-1, the currently available BCG vaccine, a modified BCG vaccine or saline.  

In trial one, 5 groups of 20 laboratory mice will be vaccinated with either M. smegmatis (unmodified parental strain of MSX-1), MSX-1, BCG, BCG-ESX1 (a modified 2^nd generation BCG-based vaccine) or saline (mock vaccine). Four out of the 20 vaccinated mice per group will be randomly selected and euthanized at day 10-, 21- and 28-days post vaccination and their spleen cells (which are enriched with immune T-cells) will be treated with tuberculin to see if there are any false positives. The remaining mice (8 per group) will be exposed to a low dose of bTB bacteria at 30 days post vaccination and monitored for an additional 40 days at which time, all mice will be euthanized to analyze the lungs and organs to assess how the bTB infection has progressed. This will inform the group if MSX-1 like BCG still provide protection against bovine TB infection but unlike BCG allow for differentiation of infected and vaccinated animals (DIVA).

In trial two, 5 groups of 8 mice per vaccine will be vaccinated as in trial one. At day 30 post-vaccination the mice will be exposed to a lethal dose of bTB bacteria and will be monitored until they die from the infection. This will tell the research team how well the vaccines are able to keep the infection at bay and enable survival of mice, and how the MSX-1 vaccine performs compared to the commercially available BCG vaccine.

Implications          

Having the ability to protect against bTB in livestock herds while still being able to rely on traditional testing methods adds a level of security to raising beef in Canada. This would be particularly valuable in areas with wildlife herds known to carry TB. The MSX-1 vaccine could mean reliable protection to alleviate the risk of producers having to cull their whole herds due to exposure and secures Canada’s bTB-free status in the global market.