CpG ODNs are synthetic oligonucleotides that contain unmethylated CpG dinucleotides in particular sequence contexts (CpG motifs)1 . These CpG motifs are present at a 20-fold greater frequency in bacterial DNA compared to mammalian DNA. CpG ODNs are recognized by Toll-like receptor 9 (TLR9) leading to strong immunostimulatory effects2 . Three classes of stimulatory CpG ODNs have been identified, classes A, B and C, which differ in their immunostimulatory activities3-4. ODN 2216 is a class A CpG ODN with a preference for human TLR9. Class A CpG ODNs are characterized by a phosphodiester central CpG-containing palindromic motif and a phosphorothioate 3’ poly-G string. They induce high IFN-α production from plasmacytoid dendritic cells (pDC) but are weak stimulators of TLR9-dependent NF-κB signaling. 1. Krieg, A. et al., 1995. CpG motifs in bacterial DNA trigger direct B-cell activation. Nature, 374:546-9. 2. Bauer, S. et al., 2001. Human TLR9 confers responsiveness to bacterial DNA via species-specific CpG motif recognition. PNAS, 98:9237-42. 3. Krug A. et al., 2001. Identification of CpG oligonucleotide sequences with high induction of IFN-alpha/beta in plasmacytoid dendritic cells. Eur J Immunol, 31:2154-63. 4. Marshall J. et al., 2005. Superior activity of the type C class o