2 A vaccine for cattle
7. The vaccination of cattle against bovine TB is
currently prohibited under EU law. Bernard Van Goethem, Director
for Veterinary and International Affairs at the European Commission,
told us 'it is not foreseen in the legislation, because so far
the vaccine does not exist'.[14]
In a letter to the Secretary of State for Environment, Food and
Rural Affairs the Commissioner for Health and Consumers summarised
the legislative situation as follows:
Vaccination against bTB is explicitly forbidden
in the EU legislation on disease control (Council Directive 78/52/EEC)
and implicitly also in intra-Union trade legislation, as vaccination
is not compatible with the provisions for testing and herd qualification
(Council Directive 64/432/EEC). EU legislation is fully in line
with OIE standards on international trade and can be changed only
by the European Parliament and the Council.[15]
Deploying a vaccine in the face of the European ban
could lead to a ban on the trade in live cattle, meat and dairy
products with other EU countries. In 2011, these trades amounted
to £496,000, £490m and £1.2bn respectively. It
is likely that countries outside of the European Union would follow
the EU's lead.
8. Before legislation and international standards
can be changed to allow vaccination to be used as part of a TB
eradication programme both the EU and OIE[16]
will need to be satisfied that a proposed vaccine is safe and
effective and that its use does not compromise the current testing
regime.
9. At present, the only vaccine for tackling TB is
the Bacille Calmette-Guérin (BCG) vaccine. Studies have
shown that the BCG cattle vaccine, as with BCG in other species,
does not guarantee complete protection but rather provides a spectrum
of protection:
· some cattle will be fully protected;
· some will benefit from reduced disease;
· some will get no protection from vaccination;
and
· vaccination does not have a therapeutic
effect on cattle that are already infected. [17]
10. A vaccine that reduces the progression, severity
and excretion of bovine TB, and thereby the risk of infection
and transmission of the disease, would be a valuable tool and
successive governments have invested heavily in developing one.[18]
Because the BCG vaccine interferes with the mandatory tuberculin
skin test used to determine whether a cow is infected with TB,
a crucial element of the work on cattle vaccination has been also
to develop a diagnostic test to differentiate between infected
and vaccinated cattle which can be used alongside the skin test—the
'DIVA test'.[19]
Managing public expectation
11. In 2010, DEFRA stated that it aimed to have the
cattle BCG and the DIVA test licensed by 2012 but that 'due to
the need to change EU legislation, which is a lengthy process,
we anticipate that a cattle vaccine and DIVA test could not be
used in the field before 2015'.[20]
In January 2012 the Government submitted an application
for 'in principle' approval of a marketing authorisation for a
cattle BCG vaccine to the Veterinary Medicines Directorate. It
said:
Licensing studies demonstrating the safety and
efficacy of BCG have now been completed by Defra's Animal Health
and Veterinary Laboratories Agency (AHVLA) and in January 2012
an application for marketing authorisation (required to place
a veterinary medicinal product on the market) was submitted to
the UK's Veterinary Medicines Directorate (VMD) for assessment.
The assessment process may take up to a year to complete and providing
it is satisfied with the safety, efficacy and quality data, VMD
will be able to confirm that requirements to obtain a marketing
authorisation have been met. However, VMD will only be able to
grant a marketing authorisation for BCG once the existing EU prohibition
on vaccination of cattle against TB is lifted.[21]
12. The application sparked widespread interest that
a vaccine might soon be available. Defra's website stated:
As the science becomes clearer Defra will be
in a firmer position in the coming months to begin to discuss
with farmers, vets and other interested parties about how the
vaccine and DIVA test can be used in the field and the likely
implications on different types of farm business.[22]
13. It would be reasonable for anyone considering
the above statements to believe that a cattle vaccine for use
against bovine TB was just a few years away. That is not the case
as correspondence between the Commission and the Government and
indeed, evidence taken during our inquiry have made clear.[23]
During our final evidence session, Professor Hewinson told us
that the 2015 date referred to in the document The Government's
approach to tackling the disease and consultation on a badger
control policy was in fact a date from which field trials
for the vaccine and DIVA test might begin. This is an unfortunate
misunderstanding for which Defra is responsible. The phrase 'used
in the field' cannot reasonably be taken to mean use only in trials.
14. With regard to the application to the VMD for
'in principle' marketing authorisation, Defra's website in October
2012 again gave the impression that the Government's research
was further advanced than was, in fact, the case. Professor Hewinson
told us that
the "in principle" application was
in fact to tease out what data would be required from the VMD
for licensing. ... One of the reasons behind putting in the "in
principle" application was to identify what data sets we
would need to create in order to get a marketing authorisation.
It is, if you like, a dummy run to getting a marketing authorisation.[24]
15. When the application was made, it would have
been helpful to public debate if the Government had been clear
that it was 'a dummy run' and that years of field trials would
likely still be required. Doing so would not have pre-judged the
work of the VMD but would have provided a clearer steer on the
likely timescale within which a vaccine might be available.
We note that the length of time for completion of the assessment
process has also changed from 'up to a year' to 'the first half
of 2013, in line with normal timelines for such applications'—a
potential increase of 50%.[25]
16. During the last 18 months the debate on the
availability of a cattle vaccine for bovine TB has been characterised
by a lack of clarity and public misunderstanding. Although it
is by no means solely responsible, the Government must accept
a great deal of the blame for this. The quality and accuracy of
the information that Defra has put in the public domain has been
insufficient and inadequate. It is unfortunate that this has led
to debate over the timetable for use of the vaccine overshadowing
scientific breakthroughs in the development of both the vaccine
and DIVA test that should be applauded.
17. Over recent months it is clear that the Government
has recognised that it should do more to inform the public. Professor
Boyd told us that the Government is working on a TB eradication
strategy that will show 'all the methods that are available for
eradication, when they are going to come on line and what their
contribution is going to be to the ultimate eradication of TB.'[26]
We await publication of the TB eradication strategy with interest
and expect it to include not only information on those methods
that are available for the eradication of bovine TB but progress
on those in development. The launch of the strategy must be accompanied
by a public information campaign to make the position clear in
the public's mind and dispel misunderstanding.
The effectiveness of the candidate
vaccine
18. The EU prohibition on cattle vaccination has
caused the Government difficulties in collecting scientific data
on the performance of the vaccine under UK field conditions. The
efficacy of the cattle BCG vaccine has been tested in 'experimentally
infected animals, with a mean level of protection (measured as
a reduction in visible pathology scores) of 70%' but these studies
cannot provide a definite figure for vaccine efficacy when administered
to cattle under field conditions in the UK.[27]
Modelling the level of efficacy required for herd immunity, both
on its own and in conjunction with other measures such as biosecurity
and movement controls is critically important. Such data are crucial
to determining whether BCG would be sufficiently effective to
justify its use.[28]
19. Small-scale studies have taken place in Ethiopia
and Mexico that have shown the protective effect of vaccination
to be between 56% and 68%. The AHVLA's study in Ethiopia involved
vaccinating calves when between one and 15 days old before they
were introduced into a herd containing a large proportion of bovine
TB-infected cattle. Defra states:
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).
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.[29]
20. Bernard Van Goethem urged us to see first whether
vaccination was useful, '... it might only be useful in 65% of
the cases ... with all the other measures that we know are efficient,
that have been applied throughout the world for decades and we
know work; 65% in addition to that: the efficiency is residual,
marginal.'[30] Professor
Hewinson agreed that cattle vaccination 'is not a magic bullet,
it is just another tool' and stressed that while 'you might conceivably
get herd immunity' if transmission was entirely from cattle to
cattle, that becomes increasingly less likely where there was
spillover from a wildlife host.[31]
Next steps
FIELD TRIALS
21. Both the European Commission and the VMD are
clear that additional data are required in order for the availability
of the vaccine to progress. The Commissioner for Health and Consumers,
Mr Tonio Borg, wrote to the Secretary of State on 14 January 2013
setting out an indicative timetable for the possible use of a
vaccine against bovine TB, putting 2023 as a tentative date for
a vaccine to be available for general use. However, Commissioner
Borg stated that the only candidate vaccine still presents many
knowledge gaps,
in particular concerning the performance of the
vaccine (level and duration of protection, protection from disease
or infection), safety (possible shedding of the attenuated live
pathogen by vaccinated animals), conditions for use (age of animals,
type of herd) and suitability of candidate DIVA test(s).
Fundamental scientific information is not yet
available on the reliability and feasibility of cattle vaccination
accompanied by use of DIVA test(s) that is fundamental for a possible
change in the current EU policy on the control and eradication
of bTB. Future studies should also address food safety concerns
(shedding of vaccine strain in milk), human health concerns
(BCG is the only vaccine available for humans and its use
in cattle may lead to the selection of BCG-resistant strains of
bTB that may affect also humans) and animal health and trade
concerns (proper discrimination between vaccinated and infected
animals, costs/benefits of vaccination policy, current policy,
acceptability of vaccinated animals in international trade).[32]
22. The VMD told us they had already formed their
views before the Commission's letter but that they were 'fairly
well aligned with the Commission on where additional data is required'.
They had 'identified issues around consumer safety, relating to
both meat and milk',[33]
but that the letter changed things in terms of process. Rather
than just list concerns that needed to be satisfied to achieve
in principle provisional marketing authorisation, in response
to the Commission's request for field trials the VMD would now
also provide details of what further data were required before
they could issue an Animal Test Certificate.[34]
Professor Hewinson explained what experimental data the VMD required:
looking at whether BCG is excreted in the milk
of lactating animals, so further assurance on whether BCG will
appear in the milk of lactating animals; looking at how long the
BCG persists at the site of injection and whether there is any
dissemination of the BCG into tissues, so that there is assurance
of the meat and milk products; and the final area is looking at
whether there is any reversion to virulence of the BCG vaccine.[35]
Mr Gibbens, Chief Veterinary Officer, Defra, expected
'a cluster of [the assurances required by the Commission] around
safety [to] be dealt with as part of the process of the VMD application'.[36]
23. While some of the points made by the Commissioner
in his letter have been questioned,[37]
it is clear that lengthy field trials are required in order to
satisfy the concerns of the EU and OIE.[38]
In his indicative timetable the Commissioner forecast the trials
to be large scale and long lasting (possibly 2-5 years).[39]
The trials will not be limited to the vaccine. The VMD told us:
The field trial or field trials will need to
look at various aspects of the claims around the vaccine. They
will not just be the claims around efficacy per se; they will
also be around the DIVA aspects. That is liable to be quite a
complex trial.[40]
24. The Commission were also clear that the trials
needed to be under EU field conditions.[41]
The UK Government's position to date has consistently been that
field trials in the UK are prohibited under EU law.[42]
This does not appear to be case. As the Minister made clear to
us, the position was not one of absolute prohibition, but rather
that consent for field trials was unlikely to be granted without
the UK being able to demonstrate it had a viable vaccine and DIVA
test:
It is no good going to the Commission asking
for a proposal for field trials, until we have not only the vaccine
that we have shown to be viable within its limits, and also the
diagnostic test, the DIVA test, which we also need to have shown
is viable. It is only when all of those factors are in place that
we could make a sensible approach.[43]
25. It is perplexing that the Government has maintained
that field trials were prohibited under EU law when, as recent
events have shown, this is not the case. We accept that field
trials might be permitted only if certain criteria are met, the
development of the DIVA test being one of them, but to have stated
that legislative change is required is misleading. It would be
unfortunate if the Government's interpretation of the legislation
had delayed progress in delivering a vaccine.
26. We are not convinced that the Government had
to wait until all the 'factors were in place' before approaching
the Commission. However, while we believe negotiations could and
should have begun earlier, we welcome the efforts of the Government
and the Commission in coming to an agreement that field trials
might take place in the UK. To be able to study the efficacy of
the vaccine and DIVA test in UK field conditions is a big step
forward and we congratulate the Government on securing this position.
27. The UK is currently putting together the programme
for the field trials in discussion with the Commission.[44]
The Commission told us
You do not design a programme in half an hour.
You have to see what you do with the animals. You have to see
what you do with the offspring of the animals. You have to see
what you do with the meat. You have to control the movement. It
is not something you can write on one piece of paper; it will
be a heavy programme, which we are helping the UK to draft, and
we are waiting to discuss that with them. I can assure you that
they are giving the highest priority to that in the veterinary
service in Defra.[45]
28. It is difficult to envisage Defra designing
field trials of the scope and size requested by the Commission
without using the commercial herd. In doing so, the Government
must take steps to reassure the public that such field trials
will not pose a public health risk. The Government must also make
sure that farmers volunteering their herds for these trials are
not left financially disadvantaged. We look forward to seeing
details of the programme for field trials once it is agreed.
THE 10-YEAR TIMETABLE
29. Before the programme of field trials can go ahead
the Government needs to generate the additional data required
for an Animal Health Certificate to be issued.[46]
It is already possible to see how the Commission's indicative
10-year timetable which forecasts field trials beginning this
year might be at risk of slipping. We pressed the Commission on
whether there was scope for the timetable to be compressed:
Bernard Van Goethem: You can always shrink the
timetable, but you have to convince the scientific community and
the international community. As I said, it is not only EU legislation;
it is also the international legislation, which needs an amendment
of the OIE code. That is a quite a lengthy process ... It is possible
to shrink it, but field trials are field trials. ... The debate
between the scientific community and legislation of course could
overlap, so it would be possible to shrink a little bit, but not
to reduce it by half, that is for sure.[47]
30. In addition to convincing the EU of the efficacy
and safety of the vaccine and effectiveness of the DIVA test,
the UK will have to convince the international community, specifically
the World Organisation for Animal Health (OIE).[48]
Mr Gibbons reassured us that the international guidelines are
being looked at in parallel, and discussions with the OIE are
already under way.[49]
31. We welcome the ongoing dialogue between the
UK, EU and OIE. A good working relationship is vital to ensuring
early success in the development and deployment of a vaccine to
help combat bovine TB. The indicative 10-year timetable set down
by the Commission is precisely that, indicative. The UK Government
should do all it can to condense the timetable without compromising
the collection of the robust field data necessary to satisfy the
VMD and European and international communities. Once the programme
for field trials is agreed we look forward to the Government publishing
its own indicative timetable for the use of a cattle vaccine.
We accept that such a timetable may be subject to change but any
changes must be clearly explained.
CHANGING LEGISLATION
32. For a cattle vaccine to be available for general
use, existing European legislation has to be amended. Mr Van Goethem
believed that the political will existed across Europe for this
change to occur, partly because other countries may want to use
the vaccine but also on grounds of cost: the largest financial
support package to eradicate animal disease is spent on the UK
and it is therefore in the interests of other Member States for
this to change. As Mr Van Goethem pointed out 'What we give to
the UK we do not give to other Member States'.[50]
33. Proposals for a new EU Animal Health Law may
make it easier to change the rules prohibiting vaccination. The
new law, which is currently being drafted, will replace all existing
legislation linked to animal health repealing approximately 60
different pieces of legislation. It aims to give an overarching
framework on all rules linked to animal health: for trade of animals,
eradication of disease, and animal health rules for products.[51]
Jacqueline Minor, Head of the Commission Representation in London,
considered the new law would be likely to make it easier to change
the rules on vaccination:
Currently they would have to be changed by primary
legislation, so it would have to be a proposal for a directive
of the Council and the Parliament. Within the framework of the
new legislation, once adopted, it would be possible to change
the rules on vaccination by a delegated measure, which would be
much quicker in principle.[52]
Mr Gibbons assured us that the UK Government have
been working to make sure that the draft contains an enabling
measure to allow the use of cattle vaccines.[53]
We invite Defra to indicate in its response to this Report,
the timetable proposed for the new Animal Health legislation.
Costs
34. Widespread use of a cattle vaccine and DIVA test
will increase the costs of a TB eradication programme, at least
in the short term. Professor Hewinson estimated the cost of the
vaccine at £5-6 per dose and the DIVA test at £25.[54]
Studies have so far suggested that vaccination will be needed
annually. Sensitisation to the skin test falls off so that after
nine months only 10% of animals test positive as a result of the
vaccination. Therefore, it may be that in a TB clear herd only
10% of animals will require the DIVA test - notwithstanding conditions
on animal movement. A clear record must be kept of animals vaccinated
to ensure the DIVA test is not used unnecessarily. This will add
an administrative cost to a programme of vaccination. The use
of a vet to ensure that vaccinated animals are correctly identified
may add a further charge. Over the longer term Defra models predict
vaccination could result in a saving:
The model predicts vaccinating cattle in yearly
tested parishes would cost around £170-180 million over the
period from introduction in 2012 to the end of the modelled period
in 2026. It predicts benefits from fewer breakdowns and less routine
testing of between £150-250 million, potentially saving up
to one fifth of the costs of the current policy measures. The
benefits from vaccinating cattle in yearly tested parishes are
likely to justify its costs over this period.[55]
35. A vaccine that is 65% effective will not immediately
solve the problems of bovine TB within the cattle industry. Over
the short term, its use will be an additional financial cost and
may lead to an increase in the administrative and testing burdens
farmers already face. While it will be a useful tool to have,
the circumstances in which it might be used, the precise objectives
of applying it and levels of protection that would be needed to
make vaccination worthwhile need careful consideration. Before
deployment the Government must undertake and publish a robust
cost-benefit analysis. The analysis must also consider the extent
to which EU financial support would be available for such a programme.
Future vaccines
36. The considerable cost of the DIVA test and vaccine
make it all the more important that research continues into a
vaccine that does not desensitise animals to the much cheaper
skin test. Professor Hewinson explained:
There are proofs of principle that there are
vaccines that do not sensitise to the skin test, but at the moment
none of them have proven as effective as BCG on their own. There
is ongoing work, but this is long-term; this is not a short fix.
The Society of Biology contest that because the current
experimental evidence indicates 'BCG vaccination of cattle has
only a minor protective effect against infection ... it may be
prudent to focus research efforts on developing vaccine protocols
that improve levels of immunity obtained with BCG, for example
by boosting with defined antigens.'[56]
37. Even if the cattle BCG vaccine becomes available
to use the Government must not stop there. The considerable cost
of the DIVA test and cattle BCG mean that research into a vaccine
that does not desensitise animals to the skin test must remain
an objective. There is also considerable merit in focusing research
on improving the immunity offered by the existing BCG vaccine.
14 Q 104 Back
15
Letter from Commissioner Borg to the Secretary of State, 14 Jan
2013, https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/183229/bovinetb-letter-paterson.pdf
Back
16
World Organisation for Animal Health Back
17
Defra website, http://www.defra.gov.uk/animal-diseases/a-z/bovine-tb/vaccination/cattle-vaccination/ Back
18
Ev 70 [Defra]; Defra's written evidences states that since 1994
Governments have invested more than £43million on vaccine
research and development and will have spent a further £15million
by the end of this spending review period. Back
19
DIVA is an acronym for Differentiating Infected from Vaccinated
Animals. Back
20
Bovine Tuberculosis: The Government's approach to tackling the disease and consultation on a badger control policy
Defra, 2010 Back
21
Defra website in October 2012 Back
22
Defra website in October 2012 Back
23
Letter from Commissioner Borg to the Secretary of State, 14 Jan
2013, https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/183229/bovinetb-letter-paterson.pdf Back
24
Q 347 Back
25
Defra website in October 2012 and Ev 70 [Defra] Back
26
Q 422 Back
27
Ev 70 [Defra] Back
28
Ev w39 [Rethink Bovine TB] Back
29
Ev 70 [Defra] Back
30
Q 141 Back
31
Q 333 Back
32
Letter from Commissioner Borg to the Secretary of State, 14 Jan
2013, https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/183229/bovinetb-letter-paterson.pdf Back
33
Qq 207-8 Back
34
To conduct field trials it is necessary to have an Animal Test
Certificate, Q 358 Back
35
Q 423 Back
36
Q 435 Back
37
For example, see http://www.bovinetb.info/vaccination.php for
comments on the concerns that widespread use of BCG might encourage
BCG resistant strains of TB and Qq 447-9 Back
38
Q 211, Q 331 and letter from Commissioner Borg Back
39
Letter from Commissioner Borg Back
40
Q 230 Back
41
Q 122, Q 348 and letter from Commissioner Borg; the OIE also require
data from UK field trials - see written evidence submitted by
Rethink Bovine TB (Ev 39) for discussion of Defra's application
to the OIE. Back
42
For example, Defra's website in October 2012 stated 'Studies to
date cannot provide a definite figure for vaccine efficacy when
administered to cattle under field conditions in the UK and it
is currently not possible to generate these data in the field
because of existing EU legislation prohibiting vaccination of
cattle against TB'. Back
43
Q 432 Back
44
Q 124; Q 436 Back
45
Q 129 Back
46
Q 359 Back
47
Q 138 Back
48
See Q 446 for further explanation of the role of the OIE Back
49
Q 440 Back
50
Q 127 Back
51
Q 152 and Q 163 Back
52
Q 163 Back
53
Q 454 Back
54
Q 377 Back
55
Options for vaccinating cattle against bovine tuberculosis,
Defra, July 2007 Back
56
Ev w31 [Society of Biology] Back
| 
