Multicomponent gold nano-glycoconjugate as a highly immunogenic and protective platform against Burkholderia mallei

Daniel Tapia,Javier I Sanchez-Villamil,Alfredo G Torres

doi:10.1038/s41541-020-00229-9

Daniel Tapia, Javier I Sanchez-Villamil + Show 1 more

Open Access

https://doi.org/10.1038/s41541-020-00229-9

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Abstract

Burkholderia mallei (Bm) is a facultative intracellular pathogen and the etiological agent of glanders, a highly infectious zoonotic disease occurring in equines and humans. The intrinsic resistance to antibiotics, lack of specific therapy, high mortality, and history as a biothreat agent, prompt the need of a safe and effective vaccine. However, the limited knowledge of protective Bm-specific antigens has hampered the development of a vaccine. Further, the use of antigen-delivery systems that enhance antigen immunogenicity and elicit robust antigen-specific immune responses has been limited and could improve vaccines against Bm. Nanovaccines, in particular gold nanoparticles (AuNPs), have been investigated as a strategy to broaden the repertoire of vaccine-mediated immunity and as a tool to produce multivalent vaccines. To synthesize a nano-glycoconjugate vaccine, six predicted highly immunogenic antigens identified by a genome-wide bio- and immuno-informatic analysis were purified and coupled to AuNPs along with lipopolysaccharide (LPS) from B. thailandensis. Mice immunized intranasally with individual AuNP-protein-LPS conjugates, showed variable degrees of protection against intranasal Bm infection, while an optimized combination formulation (containing protein antigens OmpW, OpcP, and Hemagglutinin, along with LPS) showed complete protection against lethality in a mouse model of inhalational glanders. Animals immunized with different nano-glycoconjugates showed robust antigen-specific antibody responses. Moreover, serum from animals immunized with the optimized nano-glycoconjugate formulation showed sustained antibody responses with increased serum-mediated inhibition of adherence and opsonophagocytic activity in vitro. This study provides the basis for the rational design and construction of a multicomponent vaccine platform against Bm.

Highlights

Glanders is a zoonotic disease with a high degree of transmissibility to humans and mortality in solipeds
Due to the pathogen’s inability to survive for long periods of time outside its mammalian host, Burkholderia mallei (Bm) is thought to have evolved by reductive evolution from its genetically related counterpart, Burkholderia pseudomallei (Bpm), the causative agent of melioidosis[6,7]
The highest colonization was found in the spleen of those surviving animals receiving the AuNP-OmpW-LPS formulation (Fig. 3d). These results indicate that the different AuNP-glycoconjugate formulations protect mice against a lethal inhalational challenge with Bm, being the highest protection the one provided by the optimized nanovaccine combination (AuNPCombo2-LPS)

Summary

Introduction

Glanders is a zoonotic disease with a high degree of transmissibility to humans and mortality in solipeds (e.g., horses, mules, and donkeys). Due to the pathogen’s inability to survive for long periods of time outside its mammalian host, Bm is thought to have evolved by reductive evolution from its genetically related counterpart, Burkholderia pseudomallei (Bpm), the causative agent of melioidosis[6,7]. Both of these pathogens are capable of infecting and surviving inside phagocytic and non-phagocytic cells, including lung epithelial cells[1,7].

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