A gold nanoparticle-linked glycoconjugate vaccine against Burkholderia mallei

• Published in: Nanomedicine 2015-02, Vol.11 (2), p.447-456
• Main Authors: Gregory, Anthony E., Bsc, PhD, Judy, Barbara M., Bsc, PhD, Qazi, Omar, Bsc, PhD, Blumentritt, Carla A., BSc, Brown, Katherine A., Bsc, PhD, Shaw, Andrew M., Bsc, PhD, Torres, Alfredo G., Bsc, PhD, Titball, Richard W., Bsc, PhD, DSc
• Format: Article
• Language: English
• Subjects: Administration, Inhalation; Animals; Bacterial Vaccines - administration & dosage; Bacterial Vaccines - chemistry; Burkholderia mallei - drug effects; Burkholderia mallei - pathogenicity; Disease Models, Animal; Glanders; Glanders - drug therapy; Glanders - immunology; Glanders - microbiology; Glycoconjugate; Glycoconjugates - administration & dosage; Glycoconjugates - chemistry; Gold - chemistry; Humans; Internal Medicine; Lipopolysaccharides - administration & dosage; Lipopolysaccharides - immunology; Metal Nanoparticles - administration & dosage; Metal Nanoparticles - chemistry; Mice; Nanoparticles
• ISSN: 1549-9634; 1549-9642
• DOI: 10.1016/j.nano.2014.08.005

Abstract Burkholderia mallei are Gram-negative bacteria, responsible for the disease glanders. B. mallei has recently been classified as a Tier 1 agent owing to the fact that this bacterial species can be weaponised for aerosol release, has a high mortality rate and demonstrates multi-drug resistance. Furthermore, there is no licensed vaccine available against this pathogen. Lipopolysaccharide (LPS) has previously been identified as playing an important role in generating host protection against Burkholderia infection. In this study, we present gold nanoparticles (AuNPs) functionalised with a glycoconjugate vaccine against glanders. AuNPs were covalently coupled with one of three different protein carriers (TetHc, Hcp1 and FliC) followed by conjugation to LPS purified from a non-virulent clonal relative, B. thailandensis . Glycoconjugated LPS generated significantly higher antibody titres compared with LPS alone. Further, they improved protection against a lethal inhalation challenge of B. mallei in the murine model of infection. From the Clinical Editor Burkholderia mallei is associated with multi-drug resistance, high mortality and potentials for weaponization through aerosol inhalation. The authors of this study present gold nanoparticles (AuNPs) functionalized with a glycoconjugate vaccine against this Gram negative bacterium demonstrating promising results in a murine model even with the aerosolized form of B. Mallei.