Poly-L-arginine synergizes with oligodeoxynucleotides containing CpG-motifs (CpG-ODN) for enhanced and prolonged immune responses and prevents the CpG-ODN-induced systemic release of pro-inflammatory cytokines.
This study describes an entirely synthetic vaccine composed of antigenic peptides (T cell epitopes), oligodeoxynucleotides containing CpG-motifs (CpG-ODN) and poly-L-arginine (pR). CpG-ODN are known to be potent inducers of predominantly type 1-like immune responses, while polycationic amino acids, like pR, facilitate the uptake of antigens into antigen presenting cells (APCs). We demonstrate that the application of peptides and pR/CpG-ODN results in strongly enhanced peptide-specific immune responses as compared to the application of peptides with either of the immunomodulators alone. High numbers of antigen-specific T cells can be observed even after only one injection of the vaccine for a remarkably long period of time (at least 372 days). Furthermore, the potentially harmful systemic release of pro-inflammatory cytokines induced upon injection of CpG-ODN is inhibited. Thus, the combined application of CpG-ODN and pR may represent a novel vaccine strategy in humans.
Lingnau
Karen
K
Intercell Biomedical Research and Development AG, Campus Vienna Biocenter 6, 1030, Vienna, Austria. klingnau@intercell.com
Egyed
Alena
A
Schellack
Carola
C
Mattner
Frank
F
Buschle
Michael
M
Schmidt
Walter
W
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D016207:Cytokines / Q000378:metabolism*; D004357:Drug Synergism; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology*; D010047:Ovalbumin / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D010455:Peptides / Q000494:pharmacology*; D055672:Static Electricity; D013601:T-Lymphocytes / Q000276:immunology; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000276:immunology*
D000276:Adjuvants, Immunologic; C408982:CPG-oligonucleotide; D016207:Cytokines; D009838:Oligodeoxyribonucleotides; D010446:Peptide Fragments; D010455:Peptides; D014614:Vaccines, Synthetic; C015462:polyarginine; D010047:Ovalbumin