A Novel Class of Immune-Stimulatory CpG Oligodeoxynucleotides Unifies High Potency in Type I Interferon Induction with Preferred Structural Properties

Abstract

Unmethylated deoxycytidyl-deoxyguanosin dinucleotide (CpG)-containing oligodeoxynucleotides (ODNs) have been well characterized as agonists for Toll-like receptor 9. We here describe a new class of CpG ODNs, the so-called P-Class, which combines preferred properties of known CpG ODN classes. This P-Class contains two palindromic sequences, enabling it to form concatamers, multimeric units, where each molecule is bound via Watson-Crick basepairing to a second and a third palindrome. The type I interferon-inducing potency and efficacy of the double-palindromic P-Class ODN is substantially higher than that of previously described C-Class ODNs, and they stimulate superior cytokine production upon in vivo application. The multimeric structures of the P-Class can be resolved to monomers and dimers by formulation in low-salt buffer, retaining the strong and potent immune effects. Taken together, we have discovered a novel class of CpG ODNs, the P-Class, with promising superior activity for disease application.