A year ago, Defra announced a two-phase trial of bovine TB vaccination in cattle. That followed a 鈥渕ajor step forwards鈥� by government scientists in the development of a means to detect vaccinated among infected animals, which is known as a DIVA test. In this specific case, the test is called DST-F.
It began a process that could see the existing CattleBCG vaccine 鈥榙eployed鈥� in the fight against bovine TB by 2025, and that timeline has been repeatedly referenced in subsequent government policy announcements.
This was the case most recently in May, when Defra announced a change in direction 鈥� heavily criticised by the NFU 鈥� that will see the end of licences for new intensive badger cull areas after 2022, with the focus switching to vaccination of badgers and cattle.
In the latter case, Defra again assured farmers that it was "on track" with the work to assess the DIVA skin test and the vaccine.
The research project, funded and supported by Defra and the Welsh and Scottish governments, has now run for 12 months, with an Animal and Plant Health Agency (APHA) team in place to run the trial alongside a contract research organisation, Eville & Jones.
As the project reaches the field stage, here鈥檚 what we know so far...
What will the trials involve?
There will be two phases, with the second dependent on the outcome of the first:
Phase one: Establish the DIVA skin test鈥檚 specificity and safety in unvaccinated animals from TB-free cattle herds in the Low Risk Area of England and Low TB Area in Wales. Specificity is the extent to which the test responds to bTB infection and only bTB infection, or in simple terms, the rate of false positives. The aim is to complete this element by the end of January 2022.
Phase two: Establish the safety of both the CattleBCG vaccine and the DIVA skin test in vaccinated cattle. Further establish the specificity of the DIVA skin test in different groups of vaccinated animals.
How many cattle are involved?
In phase one, researchers plan to test how well the DIVA test works on around 300 cattle from five separate herds. That could increase to up to 1,000 animals, depending on initial performance and the required level of precision for the specificity estimate.
A minimum of 1,900 cattle will be involved in phase two, from more than seven separate herds, with around 1,000 animals vaccinated with CattleBCG and another 1,000 used as a control.
Will participation in the field trials be compulsory?
No, Eville & Jones will be responsible for recruiting suitable farms and herds to participate on a voluntary basis. Costs to farmers will be covered through an incentive package.
How well does the CattleBCG vaccine work?
In the APHA鈥檚 experimental model, which attempts to mirror natural infection in the field, vaccinated animals display a range of protection.
Around a third of animals are fully protected with an absence of lung pathology, one third are partially protected (reduced pathology and bacterial load) and one third are not protected at all (similar clinical signs of bTB to unvaccinated control animals).
The extent of disease reduction from CattleBCG depends on many factors, including severity of exposure to bTB and herd immunity.
A recent New Zealand field trial using the same BCG vaccine, administered under the skin but at a much lower dose than any previous trials, gave an overall protective efficacy of more than 85%. There were two cattle confirmed with TB among 520 BCG-vaccinated animals compared to eight among 297 non-vaccinated animals.
Establishing the level of protection afforded by CattleBCG to bTB will be critical for any future application for a marketing authorisation in the UK.
Both the onset and duration of immunity will need to be demonstrated to support the recommended vaccination schedule for cattle.
When will the field trials end?
The aim is to complete them by 2024.
Isn't a TB cattle vaccination always 10 years away?
Following a successful completion of field trials, APHA will apply to the Veterinary Medicines Directorate (VMD) for marketing authorisations for both the CattleBCG vaccine and the skin test DIVA. Provided the trials go as hoped and the VMD considers the marketing authorisation applications satisfactory in terms of quality, safety and efficacy, the timeline envisages those authorisations being granted by 2025.
This would pave the way for removing or relaxing the current legal barriers to vaccinating cattle against TB in England.
The estimated timeframe for the roll-out of the vaccine and DIVA test to begin is still 2025.
皇家华人view
NFU Deputy President Stuart Roberts said:
鈥淲ith bTB continuing to devastate farms across the country, the start of field trials for a cattle vaccination programme will be of interest to many farmers. We await the outcomes to further understand its potential as part of a complete bTB eradication strategy.
鈥淎s we wait, the NFU continues to champion a comprehensive approach. We must use every option at this time to tackle bTB, including wildlife controls, which have shown incredible results in recent years and have, for the first time in decades, given many farmers a light at the end of a very long and dark tunnel.
鈥淲e've always welcomed research, but what is essential is that it translates into tangible, cost-effective benefits for farmers on this incredibly difficult journey.
鈥淭here must also be continued transparency, from both Defra and the APHA, to fully understand the effectiveness and safety of any new tools, and to ensure their most appropriate use within the future strategy.鈥�
Defra looks ahead
Defra鈥檚 Bovine TB Programme team considers the hurdles and how cattle vaccination could be deployed.
"Securing UK marketing authorisations for the CattleBCG vaccine and the DIVA test is one of many hurdles that we need to overcome ahead of deployment.
"There are also policy and practical questions. For example, where and when should we deploy these products? Who administers them? How do we ensure we have enough authorised products in the right place? How do we identify and trace vaccinated cattle?
DIVA test must be validated
"For many years, the absence of a test to detect infected animals among vaccinated animals was a barrier to deployment of CattleBCG. But to use a DIVA test to certify that vaccinated herds and animals are not infected for trade purposes, we need it to be officially validated. The UK has begun discussions with the World Organisation for Animal Heath (the OIE), responsible for international standard-setting, regarding CattleBCG and the DIVA test, DST-F.
"Until we have an authorised and validated DIVA test, any deployment of an authorised CattleBCG would necessarily be limited to herds which are both under TB restrictions and sell cattle only to slaughter, potentially via Approved Finishing Units.
"Once we have both an authorised CattleBCG and an authorised and validated DIVA test, government would be looking at piloting large-scale deployment over a defined area in partnership with local farmers, ahead of decisions on more extensive roll-out. Successful deployment would require high levels of herd participation within the defined area underpinned by suitable incentives. Voluntary deployment elsewhere may also be permitted.
"The current expectation is that CattleBCG would need to be government authorised and veterinary administered, to ensure that vaccinated cattle are traceable via official databases."
High DIVA score the first hurdle
The field trials have been carefully designed to investigate several parameters including the safety and specificity of DST-F (the DIVA test) and the safety of CattleBCG, writes the APHA's Cattle Vaccine Project Team.
Separately, the duration of the vaccine鈥檚 protection will be further assessed in new carefully-controlled experiments at our Weybridge facilities.
The first phase has now commenced with DST-F undergoing specificity and safety studies on farms across England and Wales in various categories of bTBfree cattle, such as young calves, beef breeds and pregnant and lactating dairy cattle. High test specificity (i.e the proportion of truly uninfected animals that test negative) is critical to developing a test that is economically viable by limiting the number of false positive responses. If the first phase of the trials confirms the high specificity of DST-F, Phase 2 will be launched using both CattleBCG and DST-F in up to 1,000 animals on further farms across England and Wales.