LONDON SCHOOL OF HYGIENE AND TROPICAL MEDICINE

This thesis describes design, construction and evaluation in a BALB/c mouse model, for five novel Brucella specific DNA vaccines. Brucellosis is worldwide zoonosis of economic significance that poses a significant threat to both animal and human health. Vaccination of livestock can be valuable for reducing transmission and facilitating control. Development of an efficacious non-living vaccine is therefore a valuable goal in brucellosis research. Five candidate antigens were identified within the Brucella melitensis 16M genome. In silico selection was supported by confirming transcription of the selected genes from cultured Brucella, and evidence of candidate protein immunogenicity in Brucella infected sheep. Eukaryotic and prokaryotic expression plasmids were constructed for each candidate antigen. The protective efficacy of six DNA vaccine constructs was evaluated in a BALB/c model of brucellosis. From this evaluation, two protective antigens wer