Retention of structure, antigenicity, and biological function of pneumococcal surface protein A (PspA) released from polyanhydride nanoparticles

Shannon L. Haughney, Latrisha K. Petersen, Amy D. Schoofs, Amanda E. Ramer-Tait, Janice D. King, David E. Briles, Michael J. Wannemuehler, Balaji Narasimhan

Research output: Contribution to journalArticle

40 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)8262-8271
Number of pages10
JournalActa Biomaterialia
Volume9
Issue number9
DOIs
StatePublished - Sep 1 2013

Keywords

  • Nanoparticle
  • Pneumococcal surface protein A
  • Polyanhydride
  • Streptococcus pneumoniae
  • Vaccine

ASJC Scopus subject areas

  • Biotechnology
  • Biomaterials
  • Biochemistry
  • Biomedical Engineering
  • Molecular Biology

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