The stimulation of CD8+ T cells by dendritic cells pulsed with polyketal microparticles containing ion-paired protein antigen and poly(inosinic acid)-poly(cytidylic acid)

Biomaterials. 2009 Feb;30(5):910-8. doi: 10.1016/j.biomaterials.2008.10.034. Epub 2008 Nov 25.


New adjuvants and delivery strategies are needed to optimize the ability of protein-based vaccines to elicit CD8(+) T cell responses. We have developed a model vaccine formulation containing ovalbumin (OVA) and the double-stranded RNA analog poly(inosinic acid)-poly(cytidylic acid) (poly(I:C)), a TLR3 agonist. OVA and poly(I:C) were each ion-paired to cetyltrimethylammonium bromide (CTAB) to produce hydrophobic complexes, which were co-encapsulated in pH-sensitive polyketal (PK3) microparticles (1-3 microm) using a single emulsion method. Loading levels ranged from 13.6 to 18.8 microg/mg OVA and 4.8 to 10.3 microg/mg poly(I:C). Murine splenic dendritic cells (DCs) pulsed with PK3-OVA-poly(I:C) microparticles, at antigen doses of 0.01 and 0.1 microg/mL, induced a higher percentage of IFNgamma-producing CD8(+) T cells than DCs treated with PK3-OVA particles or soluble OVA/poly(I:C). A higher antigen dose (1 microg/mL) was less effective, which can be attributed to CTAB toxicity. At the lowest antigen dose (0.01 microg/mL), PK3-OVA-poly(I:C) microparticles also enhanced TNF-alpha and IL-2 production in CD8(+) T cells. These data demonstrate the potential of polyketal microparticles in formulating effective CD8(+) T cell-inducing vaccines comprising protein antigens and dsRNA adjuvants.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Antigens / chemistry
  • Antigens / immunology*
  • CD8-Positive T-Lymphocytes / drug effects
  • CD8-Positive T-Lymphocytes / immunology*
  • Cells, Cultured
  • Dendritic Cells / chemistry*
  • Dendritic Cells / immunology*
  • Mice
  • Microspheres*
  • Poly I-C / chemistry
  • Poly I-C / immunology*


  • Antigens
  • Poly I-C