Although researchers at the University of Saskatchewan have not yet found a full-fledged cattle vaccine for bovine tuberculosis (bovine TB, or bTB), they may have found a key puzzle piece.
A team with the university’s Vaccine and Infectious Disease Organization (VIDO) recently tested two vaccines — the established Bacillus Calmette Guérin (BCG) and a newcomer on the block, MSX-1, which they hoped would provide protection without triggering the false test positives that have been so problematic for livestock vaccination in the past. With further research, they found, the latter may have potential as a vaccine for the deadly cattle disease.
The investigation found both vaccines helped mitigate the bacterial infection in lab mice in different ways.
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All of the mice vaccinated with BCG — which has long been a vaccine for TB in humans and some wildlife — survived exposure to the TB-causing bacteria Mycobacterium bovis (M. bovis), while only 80 per cent of those vaccinated with MSX-1 remained after being infected.
That meant MSX-1 was not as strong as BCG in terms of total protection. A big pro, however, was that MSX-1 did not, in fact, interfere with the accuracy of the standard tuberculin skin test, as BCG tends to do.
The false positives from the BCG vaccine have kept it from being a feasible vaccination option for livestock, risking interference with Canada’s monitoring and, in the case of a positive result, strict control efforts against the disease.
“The BCG vaccine is not compatible with the diagnostic tests for bovine TB in livestock, in the sense that if you vaccinate cattle with BCG down the road if they do get infected, you will not be able to distinguish between whether they were vaccinated or they’ve actually gotten infected with the disease-causing bacteria,” said the project’s principal investigator, Jeffrey Chen.
Cull reduction a primary goal
The project was recently highlighted by the Beef Cattle Research Council (BCRC), which was a key funder of the project. A post on their website expressed optimism over the findings and the role they may play in minimizing cattle culls.
“This means that there could be a vaccine with the potential to be approved to protect Canadian cattle herds from tuberculosis while still allowing the ability to test, which could mean culling only infected animals rather than the whole herd, meaning cost savings for cattle producers, the beef industry and the government,” the BCRC said.
“There are also implications to further vaccinate wildlife, other livestock and humans with this development. Further research into dosage and length of protection will help to improve the efficacy of the MSX-1 vaccine and potential approval of use.”
Advantage: MSX-1
Bovine tuberculosis is a reportable disease under the federal Health of Animals Act. It’s a zoonotic disease that can affect a wide range of mammals including livestock, wildlife and humans.
“For the beef cattle and dairy cattle sectors in Canada, it can be devastating in the sense that it can essentially block trade,” Chen noted.
Chen’s project started in 2018, including “piecemeal” experiments during the COVID-19 pandemic years.
The project to date has focused primarily on the 104-year-old BCG and MSX-1 vaccines.
“(BCG) jolts the immune system so that when an immunized individual encounters an actual infection with the bacteria that actually causes the disease, (the) immune system is essentially given a boost. It recognizes it and it’s able to fight off the infection much more efficiently,” Chen explained.
But because of the aforementioned false positives to skin tests , BCG isn’t permitted for livestock. This reaction does not occur in humans.
“For humans, there is a diagnostic test that was developed to allow you to differentiate between individuals who are vaccinated from those who get the disease, but there isn’t a similar test for livestock,” Chen said.
Meanwhile, according to the BCRC, MSX-1 is based on “a very different and harmless mycobacteria” called M. smegmatis that could be used to provide protection against bovine TB without interfering with the tuberculin test or causing negative side effects.
“I think that sort of gives … MSX-1 an advantage in that sense,” said Chen.
TB resurgence
Bovine TB has had an unfortunate return to the Prairies in recent years.
In 2023, cases in a Saskatchewan herd became Canada’s first since 2018. Another herd was locked down in Saskatchewan in 2024 and, most recently, a dairy cow in Manitoba’s Pembina Valley region tested positive — the first such finding in the province in over a decade.
As of Sept. 11, those cases had returned 59 positive TB tests so far, according to the Canadian Food Inspection Agency. Testing is still ongoing.
“As of today, testing and culling of infected herds is the only way to manage the disease once it is confirmed,” the BCRC noted.
“While this internationally recognized approach has helped to safeguard Canada’s bTB-free status and our ability to trade internationally, these control measures are very costly to the producers affected as well as the federal government.”
Outlook for a vaccine
There’s still much research to be done before a realistic vaccine is identified, if anything develops at all, said Chen. He makes an admittedly optimistic guess of two to two-and-a-half years before there’s a chance of an effective vaccine.
“We may get some data that said ‘No, this is a no-go.’ So we just have to do the work to find out,” he said.
The project was primarily to obtain proof of principle.
“(It) has to be vetted by the scientific community before we can broadly announce ‘Look — we’re on to something interesting here that we certainly need to look into further,’” said Chen.
Once peer-reviewed, the next stage will involve large-scale studies in cattle.
The durability of MSX-1 will also be a key focus in the next round of research.
“If you vaccinate, let’s say, today, how much protection will MSX-1 provide three months from now or six months from now and a year from now?” Chen said.
Future Johne’s disease applications?
Reynold Bergen, science director for BCRC, described the project as a good use of the national check-off dollars collected from producers by Canada Beef, which disperses funds to the council for research and tech development.
“Since they have to pay it, it’s really, really important that the use we’re putting those dollars to is stuff that will benefit all producers, ideally,” he said.
Bergen hopes the development of bovine TB vaccination tech will also play into a solution to Johne’s disease, a wasting illness of cattle and other ruminants.
According to the United States Department of Agriculture, Johnes’s is caused by a resistant species of bacteria (mycobacterium avium subspecies paratuberculosis) that belongs to the same family as tuberculosis.
“It’s not a reportable disease. There’s no trade implications from it,” said Bergen.
“But it affects a lot (of) producers and has a very real economic impact for them …. The two are related, so the technology that’s used to develop that TB vaccine could also help us to develop an effective vaccine against Johne’s disease, which is a real, clear and present issue for producers.”
Tyler Fulton, president of the Canadian Cattle Association (CCA), praised BCRC’s work in an email.
“CCA appreciates and fully supports BCRC’s focus on and dedication to producer-funded research that directly benefits Canadian beef producers. We are proud that BCRC is one of our divisions, providing unbiased scientific research on subjects that producers have identified as being of importance,” he said.
