Assoc Prof Paul Brett
University of Nevada, Reno, USA
Keynote Speech: Development of multivalent subunit vaccines for immunization against melioidosis
Burkholderia pseudomallei, the etiologic agent of melioidosis, is a CDC Tier 1 select agent that causes severe disease in both humans and animals. Diagnosis and treatment of melioidosis can be challenging and in the absence of optimal chemotherapeutic intervention, acute disease is frequently fatal. Melioidosis is an emerging infectious disease for which no licensed vaccine currently exists. Due to the potential misuse of B.pseudomallei as a biothreat agent, as well as its impact on public/animal health in endemic regions, there is significant interest in developing vaccines for immunization against diseases caused by this bacterial pathogen. Several studies have demonstrated that B.pseudomallei expresses a number of structurally conserved protective antigens. Included amongst these are multiple surface exposed polysaccharides and a variety of cell-associated/secreted proteins. Based on this information, these antigens have become important components of the multivalent subunit vaccine candidates that we are developing in our laboratory. We propose that an efficacious vaccine for immunization against melioidosis can be developed by combining polysaccharide-based conjugates with specific B.pseudomallei protein(s) to produce a single, antigenically-defined formulation. Using murine models of acute melioidosis, our current research is focused on evaluating the protective capacity of these vaccine preparations with the goal of identifying suitable candidates for advancement into Phase I clinical trials. Collectively, it is anticipated that our studies will provide valuable insights towards the rational design of a safe, affordable and effective vaccine to combat melioidosis.
Dr Brett is an Associate Professor in the Department of Microbiology and Immunology at the University of Nevada, Reno School of Medicine. Over the past 20 years, his research has focused on elucidating the molecular mechanisms used by Burkholderia pseudomallei (melioidosis) and Burkholderia mallei (glanders) to evade clearance by host immune defenses. In particular, he has been interested in determining how the lipopolysaccharides and capsular polysaccharides expressed by these important bacterial pathogens are involved in this process. While working with these organisms, he has gained expertise in areas relating to Burkholderia genetics, bacterial pathogenesis, host-pathogen interactions, carbohydrate purification and characterization, glycoconjugate synthesis and the analysis of humoral/cellular immune responses. At present, the main goal of his research is to identify correlates of antigen-induced immunity against B.pseudomallei and B.mallei and use this information to develop safe, affordable and effective melioidosis/glanders subunit vaccines.