Stainsby, Karen Joan; (1989) Development of a tuberculosis vaccine for the badger. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Badger tuberculosis is endemic in some areas of Britain and Ireland and its transmission to cattle is established. Since 1975 control of the disease has relied on culling badgers, many of which were not tuberculous. This has proven to be unacceptable both on economic and conservation grounds. Previous studies of badgers vaccinated with Bacille Calmette Guerin (BCG) and then challenged with bovine tubercle bacilli (BTB) have suggested that the badger immune response is capable of stimulation by vaccine. As BCG vaccine can not be used in the wild, the aim of the work for this thesis was to develop an alternative, but still protective vaccine. It should be acceptable to the badger when administered orally and safe in large doses. Its potential consumption by cattle should not interfere with the skin test used to diagnose tuberculosis. The introductory chapters describe the problem and management of tuberculosis in cattle and badgers. Human infection with bovine tuberculosis is also addressed. How the biology, ecology and behaviour of the badger may influence vaccination is discussed. Current knowledge of the badger immune response is reviewed and potential vaccines described. The following nine chapters describe the experimental work. Captive badgers in a colony were vaccinated with various mycobacterial preparations and challenged with virulent BTB. Their immune responses both vaccination and infection were assessed by Enzyme Linked Immunosorbent Assay (ELISA) and the lymphocyte transformation test (LTT). Clinical examination and bacteriological sampling were performed regularly and excretion of BTB monitored. Two years after vaccination, autopsy of badgers was performed. From this study and one similarly performed in guinea pigs, an oral preparation made from killed Mycobacterium vaccae was selected as a vaccine. Badgers and cattle share the same feeding grounds and it was paramount that the vaccine should not influence skin test responses to bovine or avian Purified protein derivative (PPD) either in tuberculous or non-tuberculous cattle. Studies in England and in Eire have shown that, even after massive doses of vaccine, the skin test remains unaffected. As badgers may eat the vaccine in overdose, inappropriate priming of the immune response was investigated. Up to 200 vaccine doses had no harmful influence on subsequent responses to BCG. The way that M.vaccae is killed and, to some degree, the vehicle in which it is presented, may influence immunising abilities. Bacilli were found to be more immunogenic when autoclaved than when killed by gamma irradiation. Emulsion may also have been superior to suspension in water, when used as a vehicle for vaccination. A simple method of manufacture is described, producing a vaccine which was acceptable to wild badgers. Eating more than one vaccine dose was not toxic, as demonstrated in guinea pigs, mice, cattle and badgers, sometimes using up to 200 doses. Two additional studies were performed. First, the humoral antibody response of the wild badger was examined and found to be influenced by age, infection and contact with environmental mycobacteria. Second, a glycosylation change in the immunoglobulin G (IgG) molecule, previously found in humans, also occurred in the badger and was influenced by age and tuberculosis. A five year field study of the vaccine - "Badge Vac", is in progress in Eire. This is the first attempt to vaccinate a population of badgers in their natural environment. Preliminary observations indicate that this is relatively easy.

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