Yes, the candidate vaccine is BCG (Bacille Calmette-Guérin) Danish strain trialled in cattle under the name CattleBCG. BCG is the same vaccine used to protect people and badgers from TB.
A number of studies conducted in the past 25 years, where vaccinated and unvaccinated animals were exposed to a stringent experimental infection with the bovine TB bacterium (Mycobacterium bovis or ‘M. bovis’), provide significant evidence that CattleBCG can reduce the severity of disease in cattle.
However, these were experimental challenge studies that may not necessarily reflect performance under field conditions. The effectiveness of CattleBCG in reducing disease in British cattle herds under real-life, field conditions will depend on many factors, including the level of exposure to bTB. We plan to establish the protection afforded by CattleBCG to herds by continually monitoring and assessing its performance in the field during routine use over several years, as is usual for both veterinary and human vaccines. When combined with existing disease control measures, we are confident that widespread vaccination will help to further reduce the incidence of bTB and its impact on cattle farms in England and Wales.
BCG vaccination sensitises cattle to the tuberculin tests, which are the cornerstone of our bTB eradication programme and used for international trade in live cattle. It causes most cattle (approximately 80%) to react to the tuberculin test i.e. to become false positive animals.
The World Organisation for Animal Health (WOAH), which sets standards for international trade in animals and their products, advises that cattle vaccination should not be used in countries which operate control or trade measures based on tuberculin tests. Therefore, neither the WOAH’s Manual of Diagnostic Tests and Vaccines nor its Terrestrial Animal Health Code make provision for vaccination of cattle against TB at present. The Tuberculosis in Animals (England) Order 2021 prohibits the vaccination of cattle against TB without the written consent of the Secretary of State.
There is also a need to obtain UK Marketing Authorisations from the Veterinary Medicines Directorate (VMD) to market CattleBCG in the UK and ensure it meets the required standards of quality, safety and efficacy.
Yes, APHA has developed a DIVA format of the skin test (DST-F) based on three defined antigens that induce an immune response in M. bovis-infected animals (and therefore a positive skin test result), but not in BCG vaccinates. This was developed as a companion test for use alongside CattleBCG. This development is a major breakthrough. If the DIVA skin test (DST-F) is successfully validated and approved for use it will remove the problem of BCG vaccine-related false positives with the current tuberculin test by reacting only in those animals that became infected with the bTB bacterium despite having received the vaccine, i.e. true-positives.
The WOAH recognises that significant progress has been made in the development of DIVA tests and supports the field trials under way in the UK. It envisages that vaccination could be applied in combination with such DIVA tests once these have been fully validated and the legal framework amended accordingly. In its meeting of September 2021, the members of the WOAH’s Biological Standards Commission agreed that “the BCG vaccination and DIVA skin test approach looks very promising and could provide an alternative to bTB control that could be used in certain countries in certain situations” (especially in low and middle-income countries where the traditional bTB control approach of testing and slaughtering infected cattle is not affordable or socially acceptable).
Both the candidate CattleBCG vaccine and the DIVA skin test (DST-F) need UK Marketing Authorisations from the VMD in the same way as any other veterinary medicines. We also need to do further work to validate the DST-F to WOAH standards.
APHA has embarked on field trials to evaluate further the CattleBCG vaccine and DST-F. These field trials are funded through the GB bTB Research & Development budget on behalf of Defra, Welsh Government and Scottish Government. It is hoped that they will provide the additional evidence required for future UK national Marketing Authorisation applications and for the DST-F to be internationally recognised. The field trials are being conducted to investigate the safety of CattleBCG in cattle in the field and the safety and specificity/performance of the DST-F.
Defra, Welsh Government and Scottish Government are also funding two supplementary research projects. One is looking at the minimum duration of immunity afforded by CattleBCG. The other is assessing the sensitivity of the DST-F in cattle naturally infected with TB (i.e. TB test reactors sourced from farms). These two projects are scheduled to run until 2023 and their results will feed into the dossier to be submitted to the VMD in support of the CattleBCG and DST-F Marketing Authorisation applications.
A summary of the DST-F data generated to date at APHA demonstrates promising results. The DST-F has been shown to be effective in detecting infected animals while giving negative results in vaccinated uninfected cattle. Separate field trials and experimental studies are currently underway to obtain more precise estimates of both the specificity and sensitivity of the DST-F, respectively, in both vaccinated and unvaccinated cattle.
Phase 1 of the field trials started in June 2021 and the field component is complete. Phase 2 started in January 2023. In July 2020, Defra announced that VMD had granted permission (Animal Test Certificates) for field trials. This followed detailed assessment of applications submitted by APHA in October 2019.
Following an open competition, APHA awarded a contract to Eville & Jones to run veterinary field trials. Eville & Jones, as the Contract Research Organisation (CRO), have brought together an experienced team for conducting the field trials to the internationally recognised high standards of Good Clinical Practice – Veterinary (GCPv) to deliver the project.
There are two phases, with phase 2 dependent on the outcome of phase 1:
- Phase 1: Assessing the DIVA skin test (DST-F) specificity and safety in unvaccinated animals from TB-free cattle herds in the Low Risk Area of England.
- Phase 2: Assessing the safety of both the CattleBCG vaccine and DST-F, and the specificity of DST-F in vaccinated animals (and unvaccinated controls) from TB-free cattle herds in low bTB risk areas of England and Wales.
The field trials are carried out in two phases:
- Phase 1 took place on participating farms in the Low Risk Area (England). It started in June 2021 on a farm in Hertfordshire.
- Phase 2 is taking place on participating farms in low bTB risk areas of England and Wales.
The field trials are carried out in two phases:
- Phase 1: 524 cattle from ten herds were included.
- Phase 2: The number of cattle for this phase will be approximately 600 from at least five herds, with approximately the same number of cattle in each participating herd randomly receiving either the vaccine or a placebo substance (i.e. used as controls).
Cattle vaccinated with CattleBCG during phase 2 will be required to remain in their herds until the end of their productive lives.
No, the Eville & Jones’ CRO team is responsible for recruiting suitable cattle herds, whose owners choose to participate in the trials on a voluntary basis.
If you are a farmer interested in taking part in this crucial research project, please contact Dr Lindsay Heasman at Eville & Jones by emailing email@example.com
The CRO is offering significant financial incentives for participating. You will be contributing to this world-leading research effort to bring a cattle TB vaccine and DIVA test into the toolbox of controls to combat bTB.
Farmers will not be financially disadvantaged through participating in the field trials.
The aim is to complete the field trials in 2023.
Following successful completion of field trials, APHA will then be able to apply to VMD for Marketing Authorisations for both the CattleBCG vaccine and the DIVA skin test (DST-F).
Provided the field trials go as hoped, the DST-F technology is successfully transferred to a manufacturer operating to Good Manufacturing Process and VMD considers the Marketing Authorisation applications satisfactory with respect to quality, safety and efficacy, the timeline envisages those authorisations being granted in the next few years. This would pave the way for removing or relaxing the current legal barriers to vaccinating cattle against TB in England and Wales.
No. Progress in the past was hampered because of the lack of a suitable companion DIVA test, but APHA research has now developed the DIVA skin test (DST-F). Like other veterinary medicines, in addition to laboratory studies, both CattleBCG and DST-F must be shown to be effective and safe under field conditions before VMD can authorise their use. The estimated timeframe for having a deployable CattleBCG and companion DST-F in the UK is the next few years, subject to successfully completing the field trials, successfully transferring the DST-F technology to a manufacturer operating to Good Manufacturing Process and gaining the necessary Marketing Authorisations.
The World Organisation for Animal Health (WOAH) sets animal health standards for international trade in animals and animal products as the principal reference for World Trade Organization members.
Dairy: Under WOAH standards for international trade in milk and milk products, importing countries require certification attesting that these products originate from cattle in TB-free herds or have been subjected to pasteurisation or equivalent control measures.
Meat and meat products: WOAH standards do not require any additional TB controls for international trade in fresh meat and meat products, cured hides, skins and trophies, or gelatine, collagen, tallow and meat-and-bone meal originating from animals that have been subjected to ante- and post-mortem inspections. These are considered safe commodities.
Live cattle: WOAH standards make no provision for vaccination of cattle against TB at present, as BCG vaccination interferes with internationally-accepted tuberculin-based tests which underpin current criteria for certifying herds free of TB. Enabling international trade in vaccinated live cattle will require WOAH recognition of CattleBCG and the DIVA skin test (DST-F), and amendments to WOAH standards to clarify how they apply to trade in live cattle vaccinated against TB. The same applies to any international trade in genetic products from vaccinated live cattle which relies upon negative results of tuberculin testing.
Trade requirements are agreed on a bilateral basis between trading partners. Defra will continue to engage with WOAH and trading partners to mitigate the likelihood of any trade impacts from potential future deployment of CattleBCG and DST-F. Defra has previously considered the risk of commercial cattle buyers discriminating against cattle vaccinated against TB. A limited expert elicitation project commissioned to seek the views of key UK meat sector decision makers concluded that there was no significant risk of discrimination of this nature, provided the safety of the products derived from vaccinated cattle could be assured.
Yes. The applications to conduct field trials of CattleBCG and the DIVA skin test (DST-F) underwent careful scientific assessment by VMD to ensure that the necessary requirements to conduct veterinary field trials of unauthorised veterinary medicines in a food producing species were met and to ensure safety for the target, user, consumer and environment. There is no withdrawal period for milk from cattle vaccinated with CattleBCG. The Animal Test Certificate permitting the field trials, requires a 90-day withdrawal period for meat and offal from cattle vaccinated with CattleBCG. Withdrawal periods for CattleBCG will be regulated in the same way as those for other veterinary medicines. Keepers are required to provide Food Chain Information for cattle sent to slaughter, declaring that withdrawal periods have been observed. There are no withdrawal periods for meat, offal or milk from cattle tested with the DST-F.
No. CattleBCG is administered subcutaneously (under the skin) and would therefore never be expected to enter the meat. There has never been any evidence for BCG vaccine lesions in cattle carcases.
Initial data obtained from testing sera collected at seven time-points over 12 months from animals in the ‘BCG duration of immunity’ study (project SE3333) suggests that BCG vaccination does not induce false-positive responses to the IDEXX Paratuberculosis Screening ELISA test.
Soil Association organic standards indicate that use of immunological veterinary medicines (vaccines) is permitted.
3.4.6 Use of vaccines is permitted. You may use immunological veterinary medicines.
Further consultation to develop a CattleBCG deployment policy is planned. Without an authorised and validated DIVA skin test (DST-F) to certify that vaccinated herds and animals are not infected for trade purposes, 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 internationally recognised DST-F, government may consider piloting deployment in partnership with farmers ahead of decisions on more extensive deployment. Current expectation is that CattleBCG will need to be prescribed by a veterinary surgeon, government-authorised and administered under official veterinary control. This would ensure that vaccinated cattle are identifiable and traceable via official databases.
Further consultation to develop a CattleBCG deployment policy is planned.
Under the Animal Test Certificate specification for the field trials, CattleBCG is indicated for cattle from 21 days of age. Administration is by subcutaneous (under the skin) injection. Current understanding, based on duration of immunity data, is that annual vaccination with CattleBCG would be necessary to maintain a protective effect.
APHA technical discussion paper
The Animal & Plant Health Agency (APHA) submitted a technical discussion paper to the World Organisation for Animal Health (WOAH) on 29 June 2021. The paper discussed the information available at that time on the potential role for BCG vaccination in global efforts to control and eradicate bovine TB.