Incorporation of CpG oligonucleotide ligand into protein-loaded particle vaccines promotes antigen-specific CD8 T-cell immunity

Bioconjug Chem. Jan-Feb 2007;18(1):77-83. doi: 10.1021/bc060165i.

Abstract

The development of multicomponent biotherapeutic carriers is an important challenge in the field of drug delivery, particularly in the area of protein-based vaccines. While the delivery of protein antigens to antigen presenting cells (APCs) is crucial for this type of vaccination, the incorporation of additional adjuvants may be just as important in order to generate more potent immune responses. This article presents the synthesis and biological evaluation of carrier particles that both deliver a protein payload to APCs and display receptor ligands for the enhancement of APC immunostimulation. Particles displaying CpG oligonucleotide ligands for Toll-like receptor 9 were synthesized. The addition of CpG DNA to the particles led to a 45-fold increase in the secretion of interleukin-12, a cytokine that aids in T-cell activation, and a significant increase in the expression of costimulatory molecules by APCs. Moreover, vaccination with particles containing both ovalbumin (OVA) and CpG DNA induced a superior OVA-specific CD8 T-cell response in vivo, as measured by increased OVA-specific CD8 T-cell proliferation, secretion of the proinflammatory cytokine IFN-gamma, and the induction of OVA-specific cytotoxicity.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antigens / chemistry*
  • Antigens / immunology*
  • Biomarkers
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Proliferation
  • Cells, Cultured
  • Dendritic Cells / immunology
  • Ligands
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Microscopy, Electron, Scanning
  • Oligodeoxyribonucleotides / chemical synthesis
  • Oligodeoxyribonucleotides / chemistry
  • Oligodeoxyribonucleotides / immunology*
  • Ovalbumin / chemistry*
  • Ovalbumin / immunology*
  • Vaccines / immunology*

Substances

  • Antigens
  • Biomarkers
  • CPG-oligonucleotide
  • Ligands
  • Oligodeoxyribonucleotides
  • Vaccines
  • Ovalbumin