Nonagonistic Dectin-1 ligand transforms CpG into a multitask nanoparticulate TLR9 agonist

Significance CpG oligodeoxynucleotide (ODN), a Toll-like receptor 9 ligand, is a promising immunotherapeutic agent; however, developing an IFN-inducing CpG ODN forming a stable nanoparticle without aggregation has been unsuccessful. Here we generated a nanoparticulate CpG ODN (K3) wrapped by the nonagonistic Dectin-1 ligand schizophyllan (SPG), K3-SPG. K3-SPG stimulates human peripheral blood mononuclear cells to produce large amounts of both type I and II IFN. K3-SPG thus became a potent adjuvant, especially for cytotoxic T-lymphocyte (CTL) induction to coadministered protein antigens without conjugation, which is attributable to its nanoparticulate nature rather than to targeting Dectin-1. Protective potency of K3-SPG as an influenza vaccine adjuvant was demonstrated in both murine and nonhuman primate models. K3-SPG may be used as an IFN inducer as well as a CTL inducer for immunotherapeutic applications.