Incorporation of CpG oligonucleotide ligand into protein-loaded particle vaccines promotes antigen-specific CD8 T-cell immunity.
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.
Standley
Stephany M
SM
Department of Chemistry, University of California, Berkeley, California 94729-1460, USA.
Mende
Ines
I
Goh
Sarah L
SL
Kwon
Young Jik
YJ
Beaudette
Tristan T
TT
Engleman
Edgar G
EG
Fréchet
Jean M J
JM
D000818:Animals; D000941:Antigens / Q000737:chemistry* / Q000276:immunology*; D015415:Biomarkers; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology; D008024:Ligands; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008855:Microscopy, Electron, Scanning; D009838:Oligodeoxyribonucleotides / Q000138:chemical synthesis / Q000737:chemistry / Q000276:immunology*; D010047:Ovalbumin / Q000737:chemistry* / Q000276:immunology*; D014612:Vaccines / Q000276:immunology*
D000941:Antigens; D015415:Biomarkers; C408982:CPG-oligonucleotide; D008024:Ligands; D009838:Oligodeoxyribonucleotides; D014612:Vaccines; D010047:Ovalbumin