Vaccination of Domestic and Wild Animals Against Tuberculosis 207
where interference of a natural regulated eco-
system is deemed undesirable. For these reasons,
the development and use of vaccines for control
of TB in domestic and wild animals is very
appealing.
Although no TB vaccines are currently reg-
istered for TB in cattle, there is renewed interest
in their use from the realization of the financial
impact of bovine TB on animal health and trade,
and due to the difficulty controlling the disease.
The major caveats that have restricted the use of
TB vaccines in cattle have been that protection is
not complete and vaccination can sensitize ani-
mals to respond in traditional TB diagnostic tests
(Parlane and Buddle, 2015). These problems
can now be potentially overcome by using a
vaccination integrated with other control mea-
sures, revaccination with homologous or heter-
ologous vaccines, and use of diagnostic tests
that can differentiate infected from vaccinated
animals (DIVA tests). Furthermore, experimen-
tal infection models of cattle with M. bovis and
goats with Mycobacterium caprae are now being
used to assess the efficacy of human TB vaccines
(Vordermeier et al., 2009; Pérez de Val et al.,
2013) with mutual benefits for both veterinary
and medical applications. For wildlife, use of a
vaccine to reduce or eradicate TB may be a cost-
effective strategy, and vaccination has proven to
be a successful method for control of rabies in
wild foxes in Europe (Pastoret and Brochier,
1996). The focus of this chapter is to provide an
update on the progress in vaccination of TB in
domestic and wild animals. Reviews of the his-
tory of vaccination against TB in these animals
can be found in Skinner et al. (2001), Waters
et al. (2012) and Chambers et al. (2014).
14.2 Vaccination of Cattle14.2.1 Mycobacterium bovis bacille
Calmette–Guérin vaccineThe live, attenuated bacille Calmette–Guérin
(BCG) vaccine strain of M. bovis is the only vac-
cine that is licensed for use in humans. There are
many advantages for using BCG vaccine in
domestic and wild animals as it is relatively inex-
pensive and proven safe for use in many animal
species, is produced commercially for use in
human application and DIVA tests to differenti-
ate vaccinated animals from those infected with
the wild-type strains are now available. BCG was
first used in cattle by Calmette and Guérin in
1911, who showed that protection against
M. bovis challenge was obtained by vaccination
with relatively large (20 mg) doses of BCG (see
Waters et al., 2012). Further BCG vaccination
trials were undertaken by several other groups
in the first half of the 20th century, and
although experimental challenge trials provided
encouraging results, more variable results were
reported in field trials. Potential reasons for fail-
ure to protect include the administration of high
doses of BCG (10^8 –10^10 colony-forming units
[CFU] parenterally), very high level of M. bovis
exposure, exposure of young calves to M. bovis
through consumption of milk from infected
cows prior to vaccination, lack of long-term pro-
tection and prior sensitization to environmental
mycobacteria or helminths. Informative meta-
analysis of these trials has been difficult as a
number of different BCG strains, doses and vac-
cination routes were used, together with differ-
ent methods to measure protection and varying
levels of exposure to M. bovis.
Over the past 20 years a large number of
vaccination/challenge trials have been under-
taken in cattle using harmonized models, testing
BCG alone or in comparative studies with other
vaccines. Challenge models have focused on
using a relatively low challenge dose of M. bovis
(10^3 –10^4 CFU) administered via endobronchial/
intratracheal inoculation or by aerosol (Buddle
et al., 1995; Palmer et al., 2002a). This has
resulted in the development of tuberculous
lesions mimicking those from natural disease in
the lower respiratory tract. Similar BCG strains
have been used (initially Pasteur, then BCG
Danish 1331) and protection assessed by quan-
titative gross, histopathological and micro-
biological findings. Results from a number of
studies have shown that doses of 10^4 to 10^6 CFU
of BCG administered parenterally induced
equivalent protection (Buddle et al., 1995),
while higher doses (10^8 CFU) were required to
induce protection when BCG was administered
orally (Wedlock et al., 2011). Combinations of
BCG by parenteral and mucosal routes has pro-
vided mixed results, with a small enhancement
of protection observed when BCG was adminis-
tered subcutaneously and endobronchially on