title: Protection of non-human primates against glanders with a gold nanoparticle glycoconjugate vaccine.
abstract: The Gram-negative Burkholderia mallei is a zoonotic pathogen and the causative agent of glanders disease. Because the bacteria maintain the potential to be used as a biothreat agent, vaccine strategies are required for human glanders prophylaxis. A rhesus macaque (Macaca mulatta) model of pneumonic (inhalational) glanders was established and the protective properties of a nanoparticle glycoconjugate vaccine composed of Burkholderia thailandensis LPS conjugated to FliC was evaluated. An aerosol challenge dose of ∼1×10(4) CFU B. mallei produced mortality in 50% of naïve animals (n=2/4), 2-3 days post-exposure. Although survival benefit was not observed by vaccination with a glycoconjugate glanders vaccine (p=0.42), serum LPS-specific IgG titers were significantly higher on day 80 in 3 vaccinated animals who survived compared with 3 vaccinated animals who died. Furthermore, B. mallei was isolated from multiple organs of both non-vaccinated survivors, but not from any organs of 3 vaccinated survivors at 30 days post-challenge. Taken together, this is the first time a candidate vaccine has been evaluated in a non-human primate aerosol model of glanders and represents the initial step for consideration in pre-clinical studies.
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA; Department of Pathology, University of Texas Medical Branch, Galveston, TX, 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.
authors.forename: Anthony E
authors.initials: AE
authors.lastname: Gregory
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA.
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Hatcher
authors.affiliation: Division of Microbiology, Infectious Disease Aerobiology, Tulane National Primate Research Center, Covington, LA, USA.
authors.forename: Heather
authors.initials: H
authors.lastname: Vinet-Oliphant
authors.affiliation: Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, LA, USA.
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Morici
authors.affiliation: School of Biosciences, College of Life and Environmental Sciences, University of Exeter, Devon, UK.
authors.forename: Richard W
authors.initials: RW
authors.lastname: Titball
authors.affiliation: Division of Microbiology, Infectious Disease Aerobiology, Tulane National Primate Research Center, Covington, LA, USA; Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, LA, USA. Electronic address: croy@tulane.edu.
authors.forename: Chad J
authors.initials: CJ
authors.lastname: Roy
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D000942:Antigens, Bacterial / Q000008:administration & dosage / Q000276:immunology; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000276:immunology*; D042726:Burkholderia mallei / Q000276:immunology*; D004195:Disease Models, Animal; D005896:Glanders / Q000517:prevention & control*; D006001:Glycoconjugates / Q000008:administration & dosage / Q000276:immunology; D006046:Gold / Q000008:administration & dosage*; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000276:immunology; D008253:Macaca mulatta; D053758:Nanoparticles / Q000008:administration & dosage*; D016019:Survival Analysis; D018074:Vaccines, Conjugate / Q000008:administration & dosage / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001428:Bacterial Vaccines; D006001:Glycoconjugates; D008070:Lipopolysaccharides; D018074:Vaccines, Conjugate; D006046:Gold
keywords: Aerosol; Burkholderia mallei; Glanders; Glycoconjugate; Macaques; Nanoparticles