Efficacy and Safety of BCG Vaccine for Control of Tuberculosis in Domestic Livestock and Wildlife

Abstract

Bovine tuberculosis (TB) continues to be an intractable problem in many countries, particularly where “test and slaughter” policies cannot be implemented or where wildlife reservoirs of Mycobacterium bovis infection serve as a recurrent source of infection for domestic livestock. Alternative control measures are urgently required and vaccination is a promising option. Although the M. bovis bacille Calmette-Guérin (BCG) vaccine has been used in humans for nearly a century, its use in animals has been limited, principally as protection against TB has been incomplete and vaccination may result in animals reacting in the tuberculin skin test. Valuable insights have been gained over the past 25 years to optimise protection induced by BCG vaccine in animals and in the development of tests to differentiate infected from vaccinated animals (DIVA). This review examines factors affecting the efficacy of BCG vaccine in cattle, recent field trials, use of DIVA tests and the effectiveness of BCG vaccine in other domestic livestock as well as in wildlife. Oral delivery of BCG vaccine to wildlife reservoirs of infection such as European badgers, brushtail possums, wild boar, and deer has been shown to induce protection against TB and could prove to be a practical means to vaccinate these species at scale. Testing of BCG vaccine in a wide range of animal species has indicated that it is safe and vaccination has the potential to be a valuable tool to assist in the control of TB in both domestic livestock and wildlife.

Protective Effect of Oral BCG and Inactivated Mycobacterium bovis Vaccines in European Badgers (Meles meles) Experimentally Infected With M. bovis

“…In wildlife one requirement for a vaccine is that it should be administered using baits by oral route. At the moment only BCG is allowed for intramuscular administration to badgers in the UK since 2010, but there are limitations for delivery in the field (16). Based on our data, HIMB vaccination appears to be a promising oral vaccine candidate for badgers, pending further development for large scale production, incorporation in baits, minimum protective doses, duration of immunity, safety, and assessment in field conditions.…”

“…Vaccination of badgers has been proposed as a long-term control strategy for the disease in the UK and Ireland (6)(7)(8) and experimental studies have demonstrated that vaccination with live attenuated bacillus Calmette-Guérin (BCG) vaccine is protective in badgers, and also in wild boar (9)(10)(11)(12)(13)(14)(15). However, the use of a live vaccine (BCG) at protective doses in badger is only licensed in the UK by the intramuscular route and its use in baits is controversial (16). That is because there are particular challenges associated with the development of a live oral BCG vaccine, not least maintaining the survival of BCG in baits until deployment in the field, but also with issues arising from release of a live vaccine into the environment.…”

BCG vaccination for bovine tuberculosis; conclusions from the Jerusalem One Health workshop

“…Although BCG vaccination does not induce complete protection, no single vaccine has proven to be more efficacious than BCG to protect cattle against bTB. Recent studies have shown that similar levels of protection were induced when BCG was applied parenterally or orally, although higher doses were required for oral vaccination (Buddle et al., ). The highest level of efficacy was achieved when calves were vaccinated at <1 month of age, followed by a revaccination boost at 12–24 months to prevent waning immunity (Parlane et al., ).…”

“…Therefore, induction of mucosal immunity could be beneficial and oral vaccination with BCG might be advantageous. Preliminary research into the use of oral BCG to protect cattle against bTB has been encouraging,(Buddle, Vordermeier, Chambers, & de Klerk‐Lorist, ; Nugent, Yockney, Whitford, Aldwell, & Buddle, ) as has been its application in wildlife reservoirs, such as possums in New Zealand (Tompkins et al., ) and badgers in Ireland (Gormley, Ní Bhuachalla, O'Keeffe, Murphy, & Aldwell, ). This experience, as well as the effective administration of rabies vaccine using bait, suggests that oral administration of BCG vaccine might be the most cost‐effective means of vaccinating wildlife (Pastoret & Brochier, ).…”

“…Studies over the past two decades have demonstrated that BCG vaccination of cattle can be a valuable tool in bTB control, especially in settings where “test and cull” is not an option or persistent wildlife reservoirs are difficult to eradicate (Buddle et al., ). Experimental challenge studies have identified many of the variables which influence BCG efficacy in cattle.…”