title: Evaluation of a biodegradable microparticulate polymer as a carrier for Burkholderia pseudomallei subunit vaccines in a mouse model of melioidosis.
abstract: Melioidosis, a potentially lethal disease of humans and animals, is caused by the soil-dwelling bacterium Burkholderia pseudomallei. Due to B. pseudomallei's classification as a Tier 1 Select Agent, there is substantial interest in the development of an effective vaccine. Yet, despite decades of research, no effective target, adjuvant or delivery vehicle capable of inducing protective immunity against B. pseudomallei infection has been identified. We propose a microparticulate delivery vehicle comprised of the novel polymer acetalated dextran (Ac-DEX). Ac-DEX is an acid-sensitive biodegradable carrier that can be fabricated into microparticles (MPs) that are relatively stable at pH 7.4, but rapidly degrade after phagocytosis by antigen presenting cells where the pH can drop to 5.0. As compared to other biomaterials, this acid sensitivity has been shown to enhance cross presentation of subunit antigens. To evaluate this platform as a delivery system for a melioidosis vaccine, BALB/c mice were vaccinated with Ac-DEX MPs separately encapsulating B. pseudomallei whole cell lysate and the toll-like receptor (TLR) 7/8 agonist resiquimod. This vaccine elicited a robust antibody response that included both Th1 and Th2 immunity. Following lethal intraperitoneal challenge with B. pseudomallei 1026b, vaccinated mice demonstrated a significant delay to time of death compared to untreated mice. The formulation, however, demonstrated incomplete protection indicating that lysate protein offers limited value as an antigen. Nevertheless, our Ac-DEX MPs may offer an effective delivery vehicle for a subunit B. psuedomallei vaccine.
authors.affiliation: Vaccines and Medical Countermeasures, Biological Defense Research Directorate, Naval Medical Research Center-Frederick, Ft Detrick, MD 21702, USA.
authors.forename: K L
authors.initials: KL
authors.lastname: Schully
authors.affiliation: Vaccines and Medical Countermeasures, Biological Defense Research Directorate, Naval Medical Research Center-Frederick, Ft Detrick, MD 21702, USA.
authors.forename: M G
authors.initials: MG
authors.lastname: Bell
authors.affiliation: Vaccines and Medical Countermeasures, Biological Defense Research Directorate, Naval Medical Research Center-Frederick, Ft Detrick, MD 21702, USA.
authors.forename: A M
authors.initials: AM
authors.lastname: Prouty
authors.affiliation: William G. Lowrie Department of Chemical and Biomolecular Engineering, College of Engineering, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: M D
authors.initials: MD
authors.lastname: Gallovic
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: S
authors.initials: S
authors.lastname: Gautam
authors.affiliation: Division of Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, USA.
authors.forename: K J
authors.initials: KJ
authors.lastname: Peine
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: S
authors.initials: S
authors.lastname: Sharma
authors.affiliation: Division of Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, USA.
authors.forename: E M
authors.initials: EM
authors.lastname: Bachelder
authors.affiliation: Vaccines and Medical Countermeasures, Biological Defense Research Directorate, Naval Medical Research Center-Frederick, Ft Detrick, MD 21702, USA.
authors.forename: J T
authors.initials: JT
authors.lastname: Pesce
authors.affiliation: Vaccines and Medical Countermeasures, Biological Defense Research Directorate, Naval Medical Research Center-Frederick, Ft Detrick, MD 21702, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Elberson
authors.affiliation: Division of Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, USA. Electronic address: ainsliek@email.unc.edu.
authors.forename: K M
authors.initials: KM
authors.lastname: Ainslie
authors.affiliation: Vaccines and Medical Countermeasures, Biological Defense Research Directorate, Naval Medical Research Center-Frederick, Ft Detrick, MD 21702, USA.
authors.forename: A
authors.initials: A
authors.lastname: Keane-Myers
mesh_terms: D000818:Animals; D001428:Bacterial Vaccines / Q000008:administration & dosage* / Q000276:immunology; D063566:Biodegradable Plastics / Q000737:chemistry*; D016957:Burkholderia pseudomallei / Q000276:immunology*; D003911:Dextrans / Q000008:administration & dosage / Q000737:chemistry; D004195:Disease Models, Animal; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry*; D007093:Imidazoles / Q000008:administration & dosage / Q000737:chemistry; D008554:Melioidosis / Q000276:immunology / Q000517:prevention & control*; D051379:Mice; D011108:Polymers / Q000008:administration & dosage / Q000737:chemistry*; D014611:Vaccination / Q000379:methods; D022223:Vaccines, Subunit / Q000008:administration & dosage* / Q000276:immunology
chemical_list: D001428:Bacterial Vaccines; D063566:Biodegradable Plastics; D003911:Dextrans; D004337:Drug Carriers; D007093:Imidazoles; D011108:Polymers; D022223:Vaccines, Subunit; C402365:resiquimod
keywords: Acid-labile; Bacterial vaccine; Biodegradable polymer; Bioterrorism agent; Subunit vaccine