High-affinity monoclonal antibodies that target Burkholderia Polysaccharide

Melioidosis and glanders are life-threatening illnesses caused by the bacteria Burkholderia pseudomallei and Burkholderia mallei, respectively. These gram-negative bacilli are endemic to Northern Australia and Southeast Asia, however endemic regions are expanding as surveillance improves. B. pseudomallei and B. mallei are classified as Tier 1 select agents for potential use in bioterrorism, largely due to high mortality rates, ease of mass-dispersion, and inherent resistance to antibiotics. The development of novel and effective treatment options are greatly needed improve the safety of the warfighter and general public from these pathogens. The research described in this proposal will lay the foundation for development of antibody based therapies that target the capsular polysaccharide (CPS) and the O-polysaccharide (OPS) of B. pseudomallei and B. mallei. Initial tasks (Phase I) include development of an immunization regimen in mice that is optimized for production of high affinity antibody in serum. Successful completion of this task will be followed by isolation of monoclonal antibodies; these will be characterized for binding activity and efficacy in rodent models of disease (Phase II). Finally, antibody humanization, characterization, and validation in non-human primate models will be performed (Phase III).