title: A gold nanoparticle-linked glycoconjugate vaccine against Burkholderia mallei.
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.
  
  
  BACKGROUND
  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.
authors.affiliation: School of Biosciences, College of Life and Environmental Sciences, University of Exeter, Devon, UK.
authors.forename: Anthony E
authors.initials: AE
authors.lastname: Gregory
authors.affiliation: Department of Pathology, University of TX Medical Branch, Galveston, USA.
authors.forename: Barbara M
authors.initials: BM
authors.lastname: Judy
authors.affiliation: Department of Chemistry, University of TX at Austin, Austin, USA.
authors.forename: Omar
authors.initials: O
authors.lastname: Qazi
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, USA.
authors.forename: Carla A
authors.initials: CA
authors.lastname: Blumentritt
authors.affiliation: Department of Chemistry, University of TX at Austin, Austin, USA; Cavendish Laboratory, Department of Physics, University of Cambridge, UK.
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Brown
authors.affiliation: School of Biosciences, College of Life and Environmental Sciences, University of Exeter, Devon, UK.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Shaw
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, USA; Department of Pathology, University of TX Medical Branch, Galveston, USA. Electronic address: altorres@utmb.edu.
authors.forename: Alfredo G
authors.initials: AG
authors.lastname: Torres
authors.affiliation: School of Biosciences, College of Life and Environmental Sciences, University of Exeter, Devon, UK. Electronic address: R.W.Titball@exeter.ac.uk.
authors.forename: Richard W
authors.initials: RW
authors.lastname: Titball
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D001428:Bacterial Vaccines / Q000008:administration & dosage* / Q000737:chemistry; D042726:Burkholderia mallei / Q000187:drug effects* / Q000472:pathogenicity; D004195:Disease Models, Animal; D005896:Glanders / Q000188:drug therapy* / Q000276:immunology / Q000382:microbiology; D006001:Glycoconjugates / Q000008:administration & dosage / Q000737:chemistry; D006046:Gold / Q000737:chemistry; D006801:Humans; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000276:immunology; D053768:Metal Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D051379:Mice
chemical_list: D001428:Bacterial Vaccines; D006001:Glycoconjugates; D008070:Lipopolysaccharides; D006046:Gold
keywords: Glanders; Glycoconjugate; Nanoparticles