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The search continues for TB and JD vaccines

Animal Health: Treatment for the elusive diseases grows closer

We could be lucky and find our vaccine candidates for bovine tuberculosis and Johne’s disease within a month, or it could take a year and a half. We hope within a two-year window we will have candidates ready to test out in the field.”

Dr. Andrew Potter.
photo: Supplied

These encouraging words come from Dr. Andrew Potter, CEO at the University of Saskatchewan’s VIDO-InterVac (Vaccine and Infectious Disease Organization-International Vaccine Centre) where the research group started work on developing the two vaccines about a year and a half ago.

“People have been trying for decades to develop vaccines for these diseases without much success, so we started with no preconceived ideas. We are testing everything these bacteria produce as potential candidates,” he says.

JD is caused by Mycobacterium avium ssp. paratuberculosis (MAP) and bTB is caused by Mycobacterium bovis.

“They each produce several hundred potential proteins that are potential targets for the immune system of cattle, primarily those located on the surface of the bacteria and are therefore ‘visible’ to the host upon infection,” Potter explains.

The group is working with specific individual proteins to produce sub-unit vaccines. In 1991, VIDO’s vaccine against shipping fever caused by Mannheimia haemolytica was a world-first vaccine of this type, but this approach hasn’t been used in the past for developing bTB and JD vaccines.

Vaccines against bTB and JD available in other countries are killed or live whole-cell vaccines. The main drawback of live whole-cell vaccines is that they can’t be used in animals being treated with antibiotic because the antibiotic kills the vaccine as well. Some countries have banned whole-cell JD vaccines because they interfere with diagnostic tests for bTB.

A new approach since 2000 called reverse vaccinology is being used to develop the new subunit vaccines. It begins with sequencing the genome of the pathogen. Bioinformatics software then identifies components that could be potential antigens to trigger the animal’s immune system to produce antibodies. The antigens are then cloned for testing one by one in cattle (or animal models as is the case when developing vaccines for use in people). The most suitable antigen that produces the best immune response is formulated into a vaccine prototype to be field-tested for effectiveness and safety before commercialization.

This project also involves developing a companion test for each vaccine to differentiate between vaccinated animals and those infected naturally. Potter says this won’t be difficult to do once they identify the candidates.

As a research institute, VIDO-InterVac only produces enough vaccine for the field tests and licenses its patented technologies to commercial partners who work with regulators to register the vaccines in their target markets.

“These vaccines won’t necessarily go to the highest bidder,” Potter adds. “We will carefully select our commercial partner because the vaccines must be available to Canadians first because they are the ones who paid for it.”

This project has received $7.5 million in funding through multiple sources including Genome Canada, Genome Prairie, Genome British Columbia and the Government of Saskatchewan. Animal and lab work was done at VIDO-InterVac with the University of British Columbia undertaking some of the lab work and the universities of Saskatchewan and Calgary looking after the social and economic work.

Why farmers vaccinate

Dr. Albert Ugochukwu.
photo: Supplied

Dr. Albert Ugochukwu and professor Peter Phillips with the Centre for the Study of Science and Innovation Policy, Johnson-Shoyama Graduate School of Public Policy at the University of Saskatchewan, explored the livestock industry’s responsiveness and farmers’ attitudes toward animal vaccines.

Starting with a review of the global prevalence, surveillance and control programs for bTB and JD in Europe, the U.S., Australia and Canada, they report that these two diseases are among the most prevalent endemic bovine diseases worldwide. Both are slow, progressive diseases that erode production efficiencies, profits, competitiveness and public confidence. Both pose human health risks, although that of JD has not yet been proven.

Last winter, they surveyed Canadian beef and dairy producers in search of answers to the overarching question, “what motivates farmers to use vaccines?”

The voluntary survey was carried out through dairy and beef producer associations across Canada and 234 producers responded. Of those, 105 were from the dairy side and 129 were beef producers (77 cow-calf, 25 backgrounders, 22 feedlot, and five other).

The first question identified an impediment to uptake of the new subunit vaccines given that approximately one-quarter of the respondents figured their herds weren’t at risk of getting a JD or bTB infection. Of the 75 per cent who acknowledged some risk, fewer than seven per cent viewed JD as a serious risk and fewer than two per cent viewed bTB as a serious risk.

Another question red-flagged an issue for veterinarians and producer associations to tackle because they came to the top as the sources producers most often turn to for information about vaccines at 80 per cent and 11 per cent, respectively.

The antibiotics, Draxxin and Bio-Mycin, were listed by some producers as vaccines they have used. Other than that, it was encouraging to learn that all respondents have used vaccines at one time or another because uptake of vaccines currently available suggests their acceptance of and willingness to spend money on vaccines. Most commonly they vaccinate against breeding, respiratory, clostridial, and scours diseases.

Disease prevention, at 52 per cent, is by far the main reason why producers use vaccines. Disease control and because their veterinarians recommend that they use the vaccine are neck in neck around 17 per cent. Only 5.7 per cent vaccinate to try to eliminate disease and 4.8 per cent vaccinate on the recommendation of buyers.

Almost 79 per cent of respondents participate in quality-assurance programs, such as Verified Beef Production and Canadian Quality Milk. Sixty per cent of those who participate in these programs have more than 250 cows. Of those, 37 per cent indicated that they would be interested in vaccines for JD and bTB.

Combining producers’ strong interest in quality assurance with the reasons why they use vaccines, Ugochukwu and Phillips suggest that beef and dairy farmers are most interested in disease prevention and control as a liability management response. They say this looks like a good signal for the uptake of the subunit vaccines as a complementary approach to disease prevention and control.

Willingness to pay seems to depend on interest in quality-assurance programs and herd size. Approximately 65 per cent of those willing to pay around the $15.50 mark per cow per year for a JD vaccine have herds averaging 750 dairy cows. Eighty-five per cent of those who said they’d pay more than $20 per cow have more than 1,000 dairy cattle.

Overall, 12 per cent of respondents were not willing to spend more than $5 per cow per year for a JD vaccine and 27 per cent were not willing to spend more than that for a bTB vaccine. At the opposite end of the spectrum, 10 per cent would pay more than $20 per cow per year for a JD vaccine and seven per cent would pay more than $20 for a bTB vaccine.

Most are in the middle at about 49 per cent and 44 per cent, respectively, and are willing to pay an average of $7.50 per animal per year for JD and bTB vaccines. Another 29 per cent and 23 per cent, respectively, are willing to pay an average of $15 per cow per year for JD and bTB vaccines.

As the current Alberta-Saskatchewan bTB investigation and Manitoba PED situation prove, disease outbreaks can be cumbersome and very costly to manage.

Ugochukwu and Phillips maintain that costs of dealing with outbreaks could be reduced with the use of effective and safe vaccines. The subunit JD and bTB vaccines, with companion diagnostic tests to distinguish between naturally infected and vaccinated animals, could offer an effective and profitable disease prevention, control and management option and reduce international trade distortions arising from disease outbreaks.

Economic theory has it that any situation that creates a negative externality potentially requires public-sector investment to develop effective control mechanisms. Producers may not be able to make the investment needed to provide effective control, especially when market signals aren’t there. Public-sector incentives for producers to adopt any new subunit vaccine might go a long way to encourage its use, thereby reducing long-term cost burdens and improving health and safety.

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