Dendritic cell activation and T cell priming with adjuvant- and antigen-loaded oxidation-sensitive polymersomes

Evan A. Scott, Armando Stano, Morgane Gillard, Alexandra C. Maio-Liu, Melody A. Swartz, Jeffrey A. Hubbell

Research output: Contribution to journalArticle

109 Scopus citations

Abstract

While current subunit vaccines successfully induce humoral immune responses, a need exists for vaccine strategies to elicit strong cell-mediated immunity to address diseases such as cancer and chronic viral infection. Polymersomes are stable vesicles composed of self-assembling block copolymers with tunable degradation properties allowing delivery of both hydrophilic (within vesicle interior) or hydrophobic (within vesicle membrane) payload molecules. Here we apply oxidation-sensitive nanoscale polymersomes for both antigen and adjuvant delivery to dendritic cell (DC) endosomes. Calcein-loaded polymersomes were observed to release their payload initially in multiple DC endosomal compartments and subsequently within the cytosol. With either the Toll-like receptor agonists gardiquimod or R848 as payloads within the polymersomes, release resulted in DC activation, as indicated by induction of inflammatory cytokine expression and upregulation of DC maturation surface markers: for example, the ability of gardiquimod to induce IL-6 and IL-12 cytokine expression by DCs was enhanced 10-fold when loaded within polymersomes. With the model antigen ovalbumin as a payload, release resulted in CD8 + T cell cross-priming by promoting protein antigen cross-presentation through MHC I, as indicated by activation of OT-I CD8 + T cells. Our results demonstrate that oxidation-sensitive polymersomes can function as a vaccine delivery platform for inducing cell-mediated antigen-specific immune responses.

Original languageEnglish (US)
Pages (from-to)6211-6219
Number of pages9
JournalBiomaterials
Volume33
Issue number26
DOIs
StatePublished - Sep 1 2012

Keywords

  • Copolymer
  • Drug delivery
  • Immunomodulation
  • Self-assembly

ASJC Scopus subject areas

  • Biomaterials
  • Bioengineering
  • Ceramics and Composites
  • Mechanics of Materials
  • Biophysics

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    Scott, E. A., Stano, A., Gillard, M., Maio-Liu, A. C., Swartz, M. A., & Hubbell, J. A. (2012). Dendritic cell activation and T cell priming with adjuvant- and antigen-loaded oxidation-sensitive polymersomes. Biomaterials, 33(26), 6211-6219. https://doi.org/10.1016/j.biomaterials.2012.04.060