Vaccination of European badgers (Meles meles) with BCG by the subcutaneous and mucosal routes induces protective immunity against endobronchial challenge with Mycobacterium bovis
Introduction
Wildlife infected with Mycobacterium bovis may be a source of infection for other wild animals and domestic livestock. Where transmission to livestock does occur, tuberculosis causes economic losses both from lost production and the costs associated with eradication programmes, and in addition there is a risk of zoonotic infection. Tuberculosis is endemic in a number of wild animal species: the brushtail possum (Trichosurus vulpecula) in New Zealand, white-tailed deer (Odocoileus virginianus) in North America, wild boar in Spain and Italy, and the European badger (Meles meles) in Ireland and the United Kingdom.
In the absence of a wildlife reservoir of infection, eradication of M. bovis infection from cattle can be effected by intradermal tuberculin testing to identify infected cattle and implementation of movement controls on cattle from infected herds. However, eradication of infection from domestic animals may be difficult or impossible where a reservoir of infection is present in an uncontrolled wild animal species.1 Tuberculosis in badger populations constitutes a significant reservoir of infection for domestic animals in both Ireland and the United Kingdom.2, 3 That the badger is a significant source of infection for cattle in Ireland has been demonstrated in two studies: the East Offaly study4, 5 and the four area study.3 In those studies the prevalence of tuberculosis in cattle and the number of herd breakdowns were significantly reduced when the density of the tuberculous badger population was reduced and maintained at a very low level. In the Irish bovine tuberculosis eradication program the risk of transmission of infection from badgers to cattle is reduced through focused culling of infected badgers.
Vaccination is an option for the control of M. bovis infection in badger populations.6 The purpose of vaccinating a badger population would be to decrease the burden of infection in the population and thereby decrease the risk of exposure of the cattle population. In previous studies it has been shown that the BCG is safe when injected into badgers by the intramuscular route,7 and can induce a protective response when administered intradermally.8 BCG is an appropriate choice for vaccine studies in badgers as it has a long history of safe use in humans.9 In 1994 a joint WHO/FAO/OIE consultative group recommended that BCG Pasteur 1173P2 strain be used in animal vaccine efficacy studies.10 Since then this strain has been used successfully in vaccine studies in domestic cattle,11 deer,12 and in two wild animal species, ferrets (Mustela furo)13 and brushtail possums (Trichosurus vulpecula).14 In a population of wild brushtail possums BCG Pasteur, administered directly to mucous membranes, had a protective efficacy of 69%.15
The aim of the current study was to determine if BCG Pasteur could induce a protective immune response in badgers against an endobronchial challenge with a virulent strain of M. bovis. The route of experimental infection was chosen to reflect the likely natural route of infection in badgers.16 A challenge dose of ∼104 cfu had previously been shown in badgers to give a uniform level of disease severity 12 weeks after infection, and the resulting disease had the characteristics of naturally acquired infection.17 In the current study the responses of the vaccinated and control badgers to challenge were assessed by severity of disease and infection.
Section snippets
Experimental animals: badgers
All work with badgers was carried out under licences issued by National Parks and Wildlife Service and the Department of Health and Children, and ethical approval was obtained from the UCD animal ethics committee. The 14 badgers used in the study were sourced from wild populations that were free of tuberculosis. Badgers were screened for tuberculosis by the lymphocyte transformation assay and culture for M. bovis from tracheal aspirates prior to the study. All animals were classified as
Clinical observations
There were no clinical signs observed in response to vaccination, nor were there any clinical indications of disease after challenge. All of the badgers showed a similar pattern of body weight change throughout the course of the study, with a marked and typical seasonal increase in late autumn. Two cubs were born to BR346 between 9 and 12 week pi. One cub (estimated to be have been less than a week old) was found dead at 12 weeks pi and the second cub was found dead at 15 weeks pi. Both had been
Discussion
In this study we have demonstrated that BCG vaccination induced a protective effect against experimental endobronchial challenge with virulent M. bovis in badgers vaccinated by both the subcutaneous route and the mucosal route. The protective effect of vaccination was seen as decreased severity of disease, restricted dissemination of infection, and lower bacterial burdens in lungs and thoracic LNs. The levels of infection were less severe in badgers vaccinated by the subcutaneous route compared
Acknowledgements
The help of Frances Quigley and staff in the Mycobacteriology laboratory at the Central Veterinary Research Laboratory, Backweston, Co. Kildare, is greatly appreciated. We would also like to thank Marion Barrett for her assistance with the histology. We thank Ian O'Boyle, Margaret Good, Martin Blake, and Michael Sheridan (DAFF) for their support of this study.
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