Glycoconjugate Nanoparticle Vaccines Against Burkholderia Infections

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Burkholderia mallei and B. pseudomallei are bacterial pathogens and causative agents of glanders and melioidosis, respectively. At present, effective vaccines for prevention of glanders or meliodosis have not been developed. However, renewed attention has been directed toward development of Burkholderia vaccines because of the pathogens' seemingly ideal characteristics for malicious use as a biowarfare weapon. Additionally, a vaccine will also have significant value for the immunization of at-risk populations in melioidosis/glanders endemic areas of the world. Therefore, our long-term goal is to develop a platform that allows for the efficient generation of a multicomponent vaccine which is able to protect against both glanders and melioidosis. Our approach will use glycoconjugates coupled to gold nanoparticles (NP) and test their protective properties in clinically relevant models of infection. The central hypothesis tested indicates that protein antigens of B. mallei or B. pseudomallei coupled to NP polysaccharides will elicit protection in relevant mammalian species, and that these antigens will correlate with clinically important serologic/immunologic readouts. The hypothesis will be evaluated by developing different protein-polysaccharide NPs and comparing their efficacy in vivo. The flexible NP platform will allow us to additionally incorporate novel antigens identified by other groups as further enhancing protective immunity. We will establish an optimal immunization procedure and test the efficacies of protein-polysaccharide NPs in a clinically relevant and highly controlled aerosol murine model of infection. Finally, we aim to identify the correlates/biomarkers of protection induced by protein- polysaccharide NP vaccination. This proposal is innovative because it capitalizes on the use of a subunit-NP vaccine, which could be easily licensable because of its lower cost and more widely disseminated vaccinations for at-risk populations. Together, these outcomes will help us to identify correlates of protection from protein- polysaccharide nanoparticles and provide optimized vaccination strategies.