TY - JOUR
T1 - Retention of structure, antigenicity, and biological function of pneumococcal surface protein A (PspA) released from polyanhydride nanoparticles
AU - Haughney, Shannon L.
AU - Petersen, Latrisha K.
AU - Schoofs, Amy D.
AU - Ramer-Tait, Amanda E.
AU - King, Janice D.
AU - Briles, David E.
AU - Wannemuehler, Michael J.
AU - Narasimhan, Balaji
N1 - Funding Information:
The authors thank Dr David McPherson of the University of Alabama at Birmingham for producing the recombinant PspA used in this work. The authors acknowledge financial support from NIH-NIAID (R56-AI075026). They are grateful to Ms Adeola M. Olayiwola for her assistance in optimizing the killing assay. The present work was supported by the National Science Foundation (EEC 1156933). B.N. acknowledges the support of the Vlasta Klima Balloun Professorship.
PY - 2013/9
Y1 - 2013/9
N2 - 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.
AB - 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.
KW - Nanoparticle
KW - Pneumococcal surface protein A
KW - Polyanhydride
KW - Streptococcus pneumoniae
KW - Vaccine
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U2 - 10.1016/j.actbio.2013.06.006
DO - 10.1016/j.actbio.2013.06.006
M3 - Article
C2 - 23774257
AN - SCOPUS:84880924697
SN - 1742-7061
VL - 9
SP - 8262
EP - 8271
JO - Acta Biomaterialia
JF - Acta Biomaterialia
IS - 9
ER -