Bovine TB vaccination

Written evidence submitted by the Department for Environment, Food and Rural Affairs (Defra)

Introduction

1. The Government welcomes the Committee’s inquiry, which is an opportunity to ensure that there is better understanding of the importance attached to the ongoing but technically complex work to develop and make available vaccines for tackling the problem of bovine tuberculosis (TB)

2. Bovine TB is the biggest threat to the livestock industry in England. The disease has a significant financial and emotional impact on farmers and the current control regime costs the taxpayer around £100 million a year. At present, bovine TB is still not under control and there is no single measure that would, on its own, change the situation dramatically. That is why the Government has a comprehensive , balanced and evidence-based package of measures designed to bear down on the disease in the worst affected areas and prevent its further spread. Badger vaccination by injection is one of the measures already available. We are working hard to develop and make available an oral badger vaccine and a cattle vaccine as soon as practicable.

BENEFITS AND LIMITATIONS OF VACCINATION

3. At present, the only available vaccine for tackling TB – including in the human population – is Bacille Calmette–Guérin, or BCG. BCG does not guarantee full protection and vaccinated humans and animals can still be infected and develop disease. Laboratory studies have, however, demonstrated that vaccinating badgers and cattle with BCG can reduce the progression, severity and excretion of bovine TB, thereby reducing the risk of infection and transmission of the disease.

4. The ultimate aim of a sustained bovine TB vaccination campaign would be to ensure a large enough proportion of the vaccinated animals is protected such that transmission of disease is reduced and disease cannot be sustained.  This would take time to achieve, however - if indeed it is possible, given the limited effectiveness of BCG vaccination in preventing infection and the lack of scientific evidence that the vaccine will benefit animals that are already infected.

5. Despite the limitations, making effective use of the currently available injectable badger vaccine and developing effective cattle and oral badger vaccines are high priorities for Ministers. Successive Governments have invested more than £43 million on vaccine research and development since 1994. Research is ongoing and by the end of this spending review period the Coalition Government will have spent a further £15 million.

BADGER VACCINATION

Effects of badger vaccination

6. In wild badgers, a four-year safety field-study demonstrated that BCG vaccination in a naturally infected population resulted in a statistically significant 73.8% reduction in the incidence of positive results to a badger antibody blood test for TB. Although not a true efficacy figure, this is consistent with a protective effect of vaccination as antibody production is positively correlated with the extent and severity of TB infection. Further analysis of the study data identified an indirect protective effect in unvaccinated cubs (but not adults) in vaccinated social groups such that the risk of unvaccinated badger cubs testing positive to TB decreased significantly as the proportion of vaccinated individuals in their social group increased.  When more than a third of their social group had been vaccinated, the risk to unvaccinated cubs was reduced by 79%. 

7. Benefits from vaccination of badgers would be expected to accrue incrementally during a vaccination campaign, as the number immunised increases and infected badgers die off naturally. There is no empirical evidence on the optimal length of time of a badger vaccination programme. Benefits will start to accrue from the onset of immunity and current opinion suggests that most individuals already infected with bovine TB will die off within 5 years.

8. While we would expect vaccination of badgers with BCG to result in reduced transmission of TB to cattle, we currently have no direct experimental evidence on this. Computer modelling has indicated that sustained badger vaccination campaigns could be beneficial in lowering TB incidence in cattle but its precise contribution is unknown. To be able to quantify this contribution it is likely we would need to carry out a large-scale field trial (on a comparable scale to the Randomised Badger Culling Trial) the results of which would take many years to collect.

9. Defra is working with Fera, the Animal Health and Veterinary Laboratories Agency (AHVLA) and external experts to investigate potential methods that will allow assessment of the impacts of BadgerBCG deployment on cattle TB incidence.

Use of injectable badger vaccine

10. More than 10 years of Defra research effort culminated in March 2010 in the licensing of an injectable badger vaccine (BadgerBCG). The vaccine has a Limited Marketing Authorisation from the Veterinary Medicines Directorate (VMD) – which means it is subject to renewal after 5 years - and is currently available for use by vets and trained lay vaccinators under prescription from a veterinary surgeon. There are currently 137 lay vaccinators from 34 different organisations, all of whom have completed training carried out by the Food and Environment Research Agency (Fera), as part of Defra’s Badger Vaccine Deployment Project (BVDP – see below).

11. There are three main ways in which BadgerBCG is currently being deployed:

· Government agency deployment (by way of the BVDP in England and in the Intensive Action Area in Wales);

· use by voluntary and community sector organisations (most notably by a number of Wildlife Trusts and the National Trust); and

· use by commercial contractors.

12. In England, the aims of the 4 year Defra-funded BVDP in Gloucestershire are to build confidence in the principle and practicalities of vaccination, develop practical know-how for vaccinating badgers and provide the capacity to train lay badger vaccinators.

Table. The number of premises, area and number of badgers vaccinated as part of the BVDP.

Year

Number of premises vaccinated

Area of land trapped and vaccinated (km2)

Number of badgers vaccinated

2010

93

90

541

2011

86

84

628

2012

115

95

9981

1The increase in the number of badgers vaccinated in 2012 is largely a result of recruiting additional land with high badger density.

Practicality of BadgerBCG

13. Injecting badgers with BadgerBCG requires that they are cage trapped. In practice, it is inevitable that not all badgers in an area will be trapped and vaccinated. There is also the problem that, depending on the size of the area being vaccinated, badgers from neighbouring unvaccinated areas may act as a constant source of infection.

14. Manpower is the biggest single cost. Estimates for badger vaccination can vary widely according to factors such as ease of access to setts, terrain, weather, time of year and experience of personnel. The cost will also depend on factors such as the size of area being vaccinated, density of badgers, frequency of vaccination, and model of deployment. Defra cost-benefit analysis work has estimated cage trapping and vaccination at around £2,500/km. Results emerging from the BVDP are in line with this figure and our current best estimate for the deployment of injectable Badger BCG is £2,000 - £4,000/km2.

15. While we are starting to see voluntary groups working in partnership with farmers to vaccinate badgers, the prospect of vaccination being carried out over a significant proportion of the endemic area in England remains remote. Social research, carried out as part of the BVDP, suggests that there is little interest from landowners and farmers partly because of the costs involved and partly because of the limited confidence many have in the ability of badger vaccination to reduce the incidence of TB in cattle.

Developing an oral badger vaccine

16. A badger vaccine which could be administered orally through baits would be more practical to use in the field and may, potentially, be cheaper than the currently available injectable vaccine, depending on the dose and number of baits that need to be deployed per badger to ensure adequate uptake.

17. Defra has been funding research into the development of oral vaccine candidates since 2005. Further scientific evidence is, however, needed before we can take a candidate vaccine forward to licensing. Linked to this is the need for a deployment strategy for vaccine bait which will maximise uptake among the target badger population and, as far as possible, minimise consumption by other wildlife species or cattle.

18. Until the results of the necessary, ongoing further research are known we cannot be certain of the timescale within which an effective and affordable oral badger vaccine may be available. As of now, no product is ready for licensing. In moving towards a licensable vaccine a key challenge will be to identify from a number of different formulations those which are likely to be most effective, practicable and affordable to deploy. This may rely on scientific breakthroughs and require further research and development work.

Potential c ontribution of badger vaccination to bovine TB eradication in England

19. There is no evidence that vaccination can disrupt badgers’ social group organisation and, therefore, this method of controlling bovine TB in badgers does not have the potential risks arising from perturbation associated with culling. Ineffective delivery of vaccination is also unlikely to make the disease situation worse. On the other hand, the problems with vaccination of badgers include: the lack of empirical evidence that it can contribute significantly to reducing TB in cattle; the high cost of deploying it; and its estimated effect on the weight of TB infection in badger populations, compared to controlled culling of badgers, over a given timeframe.

20. That is why the Government’s view is that badger vaccination on its own is not a sufficient response to the problem of bovine TB in badgers or cattle. As part of an eradication programme that includes badger culling, vaccination of badgers could, however, help reduce the potential negative effects of culling due to ‘perturbation’ - for example, by using vaccination as a buffer at the edge of control areas, or on land within control areas where no culling is taking place (where no other physical buffers or barriers are available).

21. Badger vaccination may also form part of an ‘exit strategy’ from culling - vaccinating remaining badgers with the aim of establishing herd immunity in previously culled areas, for example. Or it could be used to reduce spread to new areas by vaccinating at the edge of high cattle TB incidence areas. To encourage the use of badger vaccination, Defra has made available up to £250,000 per year in the form of a grant scheme, use of which in the current financial year has so far been limited to support for vaccination of badgers in the two badger cull pilot areas and to subsidise the lay vaccinator training and certification costs for voluntary and community sector organisations.

CATTLE VACCINATION

Developing a cattle vaccine

22. Following extensive research and development work carried out by AHVLA since 1999, an application for ‘in principle’ approval of a marketing authorisation (which is required to place a veterinary medicinal product on the market) for a BCG cattle vaccine was submitted to the Veterinary Medicines Directorate (VMD) for assessment in January 2012.  VMD began its assessment procedures in March 2012, following validation of the application. Further information requested by VMD was provided in November 2012. Indications are that the assessment process (which includes external, independent scientific advice) will be completed in the first half of 2013, in line with normal timelines for such applications. In practice, however, VMD will only be able to grant a full marketing authorisation when EU legislation allows vaccination of cattle against TB.

23. The efficacy of BCG vaccination of cattle has been tested in experimentally infected animals, with a mean level of protection (measured as a reduction in visible pathology scores) of 70%. As in badgers and other species, BCG vaccination provides cattle with a spectrum of protection:

· some cattle will be fully protected;

· some will benefit from reduced disease; and

· some will get no protection from vaccination.

24. Because of the EU prohibition on use of BCG vaccine in cattle, it is extremely difficult to collect robust scientific evidence on the performance of the vaccine in cattle in a natural transmission setting. AHVLA has, however, conducted a study in Ethiopia which involved vaccinating calves when between 1 and 15 days old before they were introduced into a herd containing a large proportion of bovine TB infected cattle. Although a relatively small study, vaccination of calves with BCG in this study provided significant protection against strenuous TB challenge by natural transmission. Overall, the protective efficacy of BCG was between 56% and 68% (depending on the parameters selected).

25. In terms of practical deployment of the vaccine, research results provide evidence that calves as well as older cattle can be protected by BCG vaccination to equal levels. They also suggest that annual revaccination would be desirable. The research results are still under assessment by VMD.

EU prohibition on use of BCG vaccine in cattle

26. EU legislation requires that cattle traded in the EU come only from herds with Officially Tuberculosis Free (OTF) status. This status is determined through use of the Single Intradermal Comparative Cervical Tuberculin Test (SICCT - commonly known as the tuberculin skin test) on each animal in the herd. OTF status must be suspended if animals give a positive reaction to this test.

27. BCG vaccination of cattle can interfere with the tuberculin skin test by sensitising the animal to the test, such that a vaccinated animal might produce a positive reaction regardless of its TB infection status. Mainly for that reason, current EU legislation does not allow the use of cattle vaccination against bovine TB. The European Commission has stated that if a candidate vaccine succeeds in showing scientifically sufficient protection, and no interference with diagnostic tests, it might be used as an additional tool to accelerate TB eradication under certain circumstances. But for this to be allowed, EU and international animal health rules would need to be substantially amended.

Road map for introduction of a cattle vaccine and DIVA test

28. A crucial element of the current work on cattle vaccination – because it is, in effect, a pre-requisite for the lifting of the EU ban on use of the BCG vaccine - is to validate a so called DIVA test. This is an ancillary diagnostic test developed by AHVLA that can differentiate infected from vaccinated animals, the prime candidate for which is based on the interferon-gamma bovine TB blood test. Advice from the European Commission suggests that validation of the DIVA test by the OIE (the World Organisation for Animal Health) and an opinion on cattle vaccination from the European Food Safety Authority will be pre-requisites for any Commission proposal which would provide a legal base for cattle vaccination.

29. International opinion on the approach to validation of the DIVA test has already been canvassed from three international laboratories with expertise in bovine TB. A potential weakness is that the scientific evidence we have on its performance is limited to the results of experimental studies. No EU-generated field trial data currently exists. Work on how such field trial data might be collected - ideally from field trials conducted in the UK – is currently in progress.

30. T he Government is continu ing to work with the European Commission to develop a road map for introduction of cattle vaccination and the accompanying DIVA test. This is happening at both Ministerial and official level, with goodwill on both sides. We envisage that key domestic stakeholders will have an important part to play in the process in and we will involve them in taking the work forward.

Risks of use of cattle vaccination in contravention of EU law

31. Vaccinating cattle in the UK against TB without a Marketing Authorisation for the vaccine would run the risk that trade in live cattle with other member states could be banned. It is possible that the European Commission would also consider the need for restrictions on cattle products, including meat and dairy products. Any restrictions on EU trade would also put at risk exports to third countries, with some importing authorities likely to follow the EU’s lead (including those where markets have been opened up, or restored, relatively recently). While the export market for live cattle is relatively small (valued at £496,000 in 2011), the value of beef and dairy exports is much greater and has been steadily growing in recent years. Beef exports reached almost £490 million in 2011 and dairy grew close to £1.2 billion. It is estimated that the recent lifting of the Russian ban on British beef and lamb could be worth £80 million over the next three years.

Potential c ontribution of cattle vaccination to bovine TB eradication in England

32. Vaccination of cattle against bovine TB, used in conjunction with existing TB control measures, could have benefits in reducing the prevalence, incidence and spread of TB in the cattle population and could also reduce the severity of a herd breakdown regardless of whether infection is introduced by wildlife or cattle. Early modelling work suggests, however, that while there remains a constant reservoir of badger infection cattle vaccination would not on its own eliminate bovine TB from the national herd.

33. Nevertheless, Defra is currently funding the development of two further mathematical models to look specifically at cattle vaccination within a herd and optimum ways to deploy a cattle vaccine. Defra and AHVLA officials also played leading parts in an international workshop of cattle vaccine scientists held in Cardiff in December 2012, which was designed to advance current thinking on the role that a cattle vaccine should play in TB eradication. One of the next steps is a policy workshop to address the difficult legal and operational barriers on the path to deploying a vaccine and associated DIVA in the UK.

CONCLUSION

34. Vaccination of both badgers and cattle, while not solutions to the huge problem of bovine TB in England, are potentially important components of what is necessarily a comprehensive, multi-faceted eradication programme. The barriers to wider use of the currently available injectable badger vaccine and deployment of a cattle vaccine and oral badger vaccine are sizeable and will take time to overcome. In the meantime, it is important that other means are used to bear down on the disease.

January 2013

Prepared 1st February 2013