Vaccination

The Independent Scientific Committee in Great Britain concluded that the develop­ment of a vaccine for cattle would be the best option for the long-term control of BTB (Bourne 2007).

The existing vaccine, BCG, is an attenuated strain derived from serial passage of M. bovis on glycerol-soaked potato slices by Calmette and Guerin in 1921 for use as a live vaccine to prevent the establishment of tuberculous lesions in M. bovis- challenged calves. Its effectiveness in cattle is disappointing and inconsistent (Berggren 1977; Berggren 1981; Griffin 2000; McNair et al. 2007; Hope and Villarreal-Ramos 2008), and it induces skin reactivity following vaccination that does not allow differentiation between naturally infected cattle and vaccinates (Moodie 1977). The level of protection varies significantly across studies (Waters et al. 2014), it being protective in some populations, but not others (Martin 1994). In Malawi, BCG vaccination to control the disease was attempted for a period of 8 years, but its use was unsuccessful and discontinued, and eventually there were no significant differences in the prevalence of BTB in the vaccinated and unvaccinated cattle (Ellwood and Waddington 1972; Berggren 1981).

The development of an effective vaccine for different species has been a chal­lenging and elusive process, and the ability to develop a new vaccine with an effect superior to that of BCG seems to be as difficult if not more so than the ongoing search for effective therapeutic compounds with which to treat the disease. Although the current vaccine candidates may reduce the development and size of lesions and/or bacterial loads of infected organs, there is still no vaccine candidate that can induce sterile immunity against BTB (Waters et al. 2012).

One of the major problems with the current vaccines is that they induce an immunological reaction that makes it impossible to differentiate between naturally infected animals and vaccinates. Currently, any vaccination strategy that incorpo­rates BCG is not recommended in countries where control or trade based on such testing are in operation (OIE 2009). An additional future challenge for the develop­ment of an effective vaccine and its use in cattle and wildlife species thus is the development of a diagnostic test that can differentiate between infected and vacci­nated animals (the so-called DIVA test). Vordermeier et al. (2014) reviewed the recent advances in the development of new vaccines and the differentiation between vaccinated and naturally infected cattle.

Funding around the globe involved in the control and eradication of BTB is currently focused on the development of wildlife vaccines. As is the case in cattle, the protective effect of BCG vaccination differs substantially in various wildlife species in which it was tested. Vaccination significantly reduced the incidence of positive responses to a serological test that is correlated with the extent and severity of BTB infection in badgers (Wilson et al. 2011), and in wild boar oral re-vaccination with BCG yielded a strong protective response against challenge with a field strain of M. bovis (Gortazar et al. 2014). The vaccine efficacy exceeded 95% in possums (Tompkins et al. 2009), but in a controlled study, BCG vaccination had no protective effect in African buffaloes under semi-free-ranging conditions (Michel 2008). In buffaloes, modeling indicated that annual vaccination of more than 70% of the population would be needed to reduce the herd prevalence to less than 1%, assuming a lifelong protection. It was hence concluded that, although vaccination may provide a means of controlling BTB, it cannot be used as a stand­alone strategy and should be combined with other control measures if eradication is the objective (Cross and Getz 2006).

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