Polymer micelles with pyridyl disulfide-coupled antigen travel through lymphatics and show enhanced cellular responses following immunization

Jackson K. Eby, Karen Y. Dane, Conlin P. O'Neil, Sachiko Hirosue, Melody A. Swartz, Jeffrey A. Hubbell

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

Poly(ethylene glycol)-stabilized poly(propylene sulfide) core (PEG-PPS) nanoparticles (NPs) smaller than 50 nm efficiently travel to draining lymph nodes and interact with antigen-presenting cells (APCs) to induce potent immune responses following intradermal immunization. To determine if a similar system could be developed that could be more easily and reproducibly prepared and eliminated faster in vivo, we created block copolymers of PEG-bl-PPS capable of self-assembling into 25-35 nm micelles (MCs). Biodistribution studies showed that these MCs were able to travel to draining lymph nodes, where they preferentially interacted with APCs. To couple cysteine-containing antigens to the surface of the MCs, a new polymer was synthesized with a terminal pyridyl disulfide (PDS), forming PDS-PEG-bl-PPS-benzyl. When mice were immunized in conjunction with free CpG as an adjuvant, ovalbumin-conjugated MCs (MC-Ova) generated more (2.4-fold) Ova-specific CD8+ T cells in the blood and higher (1.7-fold) interferon-gamma levels from splenocytes upon restimulation than in mice immunized with free Ova and CpG. When comparing this MC platform to our PEG-PPS NPs with disulfide-linked Ova, no significant differences were found in the measured responses. These results indicate that PDS-functionalized MCs are efficient antigen delivery vehicles that enhance immune responses compared to immunization with free protein.

Original languageEnglish (US)
Pages (from-to)3210-3217
Number of pages8
JournalActa Biomaterialia
Volume8
Issue number9
DOIs
StatePublished - Sep 1 2012

Keywords

  • Copolymer
  • Immunostimulation
  • Micelle
  • Nanoparticle
  • Self-assembly

ASJC Scopus subject areas

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

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