Evaluation of a gold nanoparticle platform as highly immunogenic and protective therapy against Burkholderia mallei, B. pseudomallei, and Enterohemorrhagic Escherichia coli O157:H7

Abstract

Burkholderia mallei (Bm) and B. pseudomallei (Bpm) are facultative intracellular pathogens and the causative agents of glanders and melioidosis. At present, effective vaccines for the prevention of glanders, or melioidosis in humans, are not available. However, renewed attention has been directed toward developing Burkholderia vaccines because of the pathogens' seemingly ideal characteristics for malicious use as a biothreat agent. Additionally, a vaccine will also have significant value for the immunization of at-risk populations in melioidosis/glanders endemic areas of the world. Therefore, the following studies' long-term goal is to develop a platform that allows for the efficient generation of a multicomponent vaccine that can protect against both glanders and melioidosis. In this study, glycoconjugates coupled to gold nanoparticles (AuNPs) were tested for their protective properties in clinically relevant infection models. The flexible NP platform allow us to incorporate novel antigens identified previously by a reverse vaccinology model. In these studies, we have established an optimal immunization procedure to test the efficacies of several protein-polysaccharide NPs when delivered alone or in a combination containing various proteins in a clinically relevant and highly controlled aerosol murine model of infection. We have demonstrated that several glycoconjugates offer protection against lethality when delivered intranasally, with increased protection afforded by a refined formulating containing the most immunogenic proteins. Also, we have shown that antigen-specific humoral responses play a significant role in the protection induced by various AuNP-coupled glycoconjugate formulations. Similarly, we have shown a protective effect of AuNP-coupled proteins in a colonization model of Enterohemorrhagic Escherichia coli (EHEC). Furthermore, we showed that vaccination with AuNP-coupled to EHEC-specific antigens elicits strong systemic and mucosal response associated with protection against EHEC colonization. This work proposes to bridge the properties of subunit vaccination with those of synthetic nanomaterials to enhance immune responses to vaccines against pathogenic bacteria.