Immunostimulatory DNA as adjuvant: efficacy of phosphodiester CpG oligonucleotides is enhanced by 3' sequence modifications.
The immunostimulatory activity of oligonucleotides containing CpG motifs is well established and represents the basis for an effective vaccine adjuvant. For use in vivo CpG ODN have to be protected from the attack of nucleases to ensure sustained effectiveness. This is usually accomplished by phosphothioate (PTO) modifications of the ODN's backbone. However, PTO modification may induce undesired effects. We, therefore, have attempted to enhance the immunostimulatory activity of CpG phosphodiester ODN by supplementation of the ODN's sequence. We report here, that addition of poly-guanosine runs to the 3'-end of a CpG-PO ODN conveys immunostimulatory activity to CpG-PO ODN in vivo and in vitro. Guanosine-rich PO ODN thus might be an alternative approach to develop effective and safe vaccine adjuvants.
Zimmermann
Stefan
S
Institute of Medical Microbiology and Hygiene, Philipps University Marburg, Pilgrimstein 2, D-35037, Marburg, Germany.
Heeg
Klaus
K
Dalpke
Alexander
A
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D066298:In Vitro Techniques; D018320:Leishmania major; D016773:Leishmaniasis, Cutaneous / Q000276:immunology / Q000517:prevention & control; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000096:biosynthesis; D009838:Oligodeoxyribonucleotides / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology*; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000276:immunology
D000276:Adjuvants, Immunologic; C408982:CPG-oligonucleotide; D016207:Cytokines; D009838:Oligodeoxyribonucleotides; D009569:Nitric Oxide