Introduction
Bovine tuberculosis (BTB) is a zoonosis caused mainly byMycobacterium bovis . BTB results in productivity loss, imposition
of trade barriers and risk of spread of infection to other domestic
livestock, wildlife, and humans. The current annual worldwide cost of
BTB is estimated at US$3 billion (Maggioli, Palmer, Thacker,
Vordermeier, & Waters, 2015). Conventionally, in developed countries,
control of BTB is based on test and slaughter policies in which
tuberculin skin test positive cattle are deemed to be infected withM. bovis and killed. However, this approach is not applied
universally. Particularly in many low- and middle-income countries
(LMIC), in which this type of control is unaffordable or societally
unacceptable
(https://www.oiebulletin.com/wp-content/uploads/bulletins/panorama-2019-1-en.pdf).
In these countries, vaccination could be used as a sustainable
supplementary tool to control policies based on test and slaughter. The
lead candidate vaccine against BTB is the live attenuated M.
bovis bacillus Calmette-Guerin (BCG); widely used to vaccinate humans
against tuberculosis. Like in humans, BCG has also shown variable
efficacy in cattle, both at population and individual animal levels (H.
M. Vordermeier, Jones, Buddle, Hewinson, & Villarreal-Ramos, 2016). The
reasons for this variability are largely unknown, although
pre-sensitisation with environmental mycobacteria interfering with
BCG-induced immunity has been put forward as a possible explanation
(Brandt et al., 2002) (Buddle, Wards, Aldwell, Collins, & de Lisle,
2002; Hope et al., 2005).
Humped cattle (Zebu, Bos taurus ssp. indicus ) are
considered more resistant to some infectious diseases, including BTB,
than non-humped cattle (B. taurus ssp taurus ) (Murray et
al., 2013). Studies in Ethiopia have shown that Zebu cattle have a lower
prevalence of skin test positivity under similar husbandry settings than
Holstein-Friesian (HF) cattle (Ameni et al., 2007). There are also
preliminary results indicating that Zebu (Boran) cattle were more
resistant to a low dose experimental M. bovis infection than
Holstein cattle (M. Vordermeier et al., 2012). However, these
preliminary data using small numbers of animals need to be confirmed.
Previous experiments compared the protection conferred by BCG
vaccination between Zebu and European cattle breeds; whilst Zebu cattle
were better protected, the number of European and crossbreed cattle used
was too small to allow to draw of statistically robust conclusions on
whether BCG-vaccinated Zebu cattle were differentially protected
compared to other breeds (Ellwood & Waddington, 1972).
Therefore, in this study we set out to compare the protective efficacy
of BCG in Zebu and HF cattle in an experimental setting. We used an
established BCG challenge model (Villarreal-Ramos et al., 2014) to
compare the relative innate (in naïve animals) and adaptive (in
vaccinated animals) immune response capabilities of Zebu and HF cattle
to control mycobacteria in vivo using age- and gender-matched
animals housed at the same location for the duration of the experimental
period.