title: Retention of structure, antigenicity, and biological function of pneumococcal surface protein A (PspA) released from polyanhydride nanoparticles.
abstract: Pneumococcal surface protein A (PspA) is a choline-binding protein which is a virulence factor found on the surface of all Streptococcus pneumoniae strains. Vaccination with PspA has been shown to be protective against a lethal challenge with S. pneumoniae, making it a promising immunogen for use in vaccines. Herein the design of a PspA-based subunit vaccine using polyanhydride nanoparticles as a delivery platform is described. Nanoparticles based on sebacic acid (SA), 1,6-bis-(p-carboxyphenoxy)hexane (CPH) and 1,8-bis-(p-carboxyphenoxy)-3,6-dioxaoctane (CPTEG), specifically 50:50 CPTEG:CPH and 20:80 CPH:SA, were used to encapsulate and release PspA. The protein released from the nanoparticle formulations retained its primary and secondary structure as well as its antigenicity. The released PspA was also biologically functional based on its ability to bind to apolactoferrin and prevent its bactericidal activity against Escherichia coli. When the PspA nanoparticle formulations were administered subcutaneously to mice they elicited a high titer and high avidity anti-PspA antibody response. Together these studies provide a framework for the rational design of a vaccine against S. pneumoniae based on polyanhydride nanoparticles.
authors.affiliation: Department of Chemical and Biological Engineering, Iowa State University, Ames, IA 50011, USA.
authors.forename: Shannon L
authors.initials: SL
authors.lastname: Haughney
authors.forename: Latrisha K
authors.initials: LK
authors.lastname: Petersen
authors.forename: Amy D
authors.initials: AD
authors.lastname: Schoofs
authors.forename: Amanda E
authors.initials: AE
authors.lastname: Ramer-Tait
authors.forename: Janice D
authors.initials: JD
authors.lastname: King
authors.forename: David E
authors.initials: DE
authors.lastname: Briles
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Wannemuehler
authors.forename: Balaji
authors.initials: B
authors.lastname: Narasimhan
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology; D001426:Bacterial Proteins / Q000008:administration & dosage* / Q000737:chemistry / Q000276:immunology*; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000138:chemical synthesis / Q000276:immunology; D003652:Decanoic Acids / Q000737:chemistry*; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000138:chemical synthesis*; D004058:Diffusion; D008422:Materials Testing; D051379:Mice; D053769:Nanocapsules / Q000008:administration & dosage / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D049388:Polyanhydrides / Q000737:chemistry*; D011091:Polyesters / Q000737:chemistry*; D011487:Protein Conformation; D013296:Streptococcus pneumoniae / Q000187:drug effects / Q000276:immunology*
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D001428:Bacterial Vaccines; D003652:Decanoic Acids; D003692:Delayed-Action Preparations; D053769:Nanocapsules; D049388:Polyanhydrides; D011091:Polyesters; C051592:pneumococcal surface protein A; C466992:poly((1,6-bis-4-carboxyphenoxyhexane)-co-(sebacic anhydride))
keywords: Nanoparticle; Pneumococcal surface protein A; Polyanhydride; Streptococcus pneumoniae; Vaccine