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.