New vaccine on horizon for bovine tuberculosis

Cattle tested positive for the disease after receiving a previous vaccine; the new vaccine is said to solve that problem

Bovine tuberculosis is a chronic, contagious, bacterial disease. Infected cattle are culled, and the farm quarantined.

Worldwide, it is one of the biggest challenges facing the cattle industry today. It has been estimated that more than 50 million cattle are infected globally costing an estimated US$3 billion annually.

According to the Canadian Food Inspection Agency, the last incidence of bovine TB in Canada was in 2018 when, on Nov. 9, laboratory testing confirmed bovine TB in four infected animals on a farm in the southern interior of British Columbia. The strain of TB was distinct from any previously known case in Canadian livestock. Nor had the strain been identified by the United States Department of Agriculture.

Animals infected with bovine TB spread the disease by shedding bacteria in tiny droplets from respiratory aerosols, feces, milk, urine, vaginal secretions and semen.

The disease can be transmitted to humans.

A vaccine for bovine TB exists and is known as the BCG Bacille Calmette-Guerin vaccine. However, it is incompatible with the PPD skin test, which is used to determine if an animal has already been vaccinated or actually has TB. The vaccine as it exists right now has a variable efficacy and it interferes with the PPD test.

The unreliability arises because cattle vaccinated with the BCG vaccine, which contains a harmless strain of the bovine TB pathogen Mycobacterium bovis, produce a positive PPD test for TB, which is why it is impossible to know, when skin tested, if they are vaccinated or truly sick.

As a result, vaccinating cows with BCG is banned in most counties, enabling vets to continue to use the PPD skin test with confidence to properly diagnose the presence or absence of the disease.

Now, scientists at the University of Surrey in the United Kingdom have developed a new vaccine and complementary skin test that could be a game changer. Once further testing is done, the vaccine will be available for cows and the skin test will independently either identify the vaccine or identify the presence of disease.

To develop the new BCG vaccine, the researchers sought to make a strain lacking some of the proteins shared with the pathogen Mycobacterium bovis by identifying genes that contain encoded immunogenic proteins that could be removed from BCG without affecting its ability to work as a live vaccine. To do this, a collection of BCG strains that had each lost a single gene were injected into cows and survival rates measured. This allowed the team to identify genes that could be removed without compromising the BCG vaccine’s effectiveness.

“What we did was we took some genes out that encode some of the protein that target the immune system,” said Johnjoe McFadden, professor of molecular genetics.

These dispensable genes encoding immunogenic proteins were deleted from the BCG chromosome to make a BCG-minus strain. The deleted immunogenic proteins were then used to develop a new synthetic skin test that, like PPD, would be positive for animals that have been exposed to TB but, unlike PPD, would be negative for animals that have been vaccinated with the BCG-minus strain.

“In parallel with that, we developed a cocktail of proteins that would protect against bovine TB but don’t detect our vaccine,” said McFadden. “A cocktail of proteins would be used as a control program where you can vaccinate as many cows as you want and still keep the diagnostic capability of doing this skin test.”

The new vaccine and the skin test were tested on guinea pigs with positive results. The tests demonstrated the effectiveness of the new BCG strain while being diagnostically compatible with a novel skin test that could be implemented in control programs.

“We used 10 cows and the skin test worked pretty well,” said McFadden. “We haven’t tested the actual vaccine yet on cows as that takes a bigger study. We need funding to do this and we should hear on that in the next few months. The study will take a few years by the time we select the cows, give them the vaccination, then test the vaccine and the diagnostic test. There’s a lot of support for this study from farmers. They hate culling their cattle. What happens is that one or two animals may come down with TB so the entire herd has to be culled. You are killing healthy animals. It’s a very crude control method.”

McFadden said he hopes that once further testing is carried out, pharmaceutical companies will come on board.

“We haven’t gone to the pharmaceutical companies yet as it is too early,” he said. “They will want to see the study in cows. They don’t have the facility to do the testing in cows so they will wait to see our results; then we will see if manufacturers have an interest in making the vaccine. It’s is an exciting project to be working on.”

The study was published in Scientific Reports.

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