Sub-Unit Vaccines for Brucella

Jenner, Dominic Charles (2009). Sub-Unit Vaccines for Brucella. PhD thesis The Open University.



Brucella species are the causative agents of brucellosis, which is regarded as the world's most prevalent zoonotic disease. Brucellosis is endemic to the Middle East, Mexico, Asia, South America and the Mediterranean and causes significant economic losses in livestock in these areas of the world, as well as being a reservoir for human brucellosis. Although there are live attenuated vaccines available for brucellosis, they have many drawbacks when used in animals, and are still infectious to humans. It is clear from this that there is a need for a new effective vaccine for brucellosis for both animal and human use.

There are increasing instances of ATP-binding cassette (ABC) systems being identified as virulence factors or potential vaccine candidates. In this study inventories of all the ABC systems encoded by five sequenced Brucella strains were compiled. These inventories were compared and differences have been found that could aid in the identification of virulence factors of Brucella. This study also explores the potential of ATP-binding cassette transporters as sub-unit vaccines against Brucella melitensis 16M. Eight ABC transporter proteins (PotD, PotF, Cgt, CydD, LolE, FbpA, OppA and ZnuA) have been produced using recombinant protein technologies, and their protective efficacy was evaluated in a number of studies using the murine model of B. melitensis infection. Of the eight vaccine candidates selected two have shown potential as novel vaccines against brucellosis. PotD and PotF are putative polyamine binding proteins of Brucella and show protection against experimental challenge of approximately 1x104 CFU of B. melitensis 16M when expressed by DNA vaccines or used in a PotD/PotF combination vaccine. Through this work a duel adjuvant system (ISCOMs and CpG) has been identified as a more effective adjuvant for Brucella vaccines than others previously used.

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