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Nonagonistic Dectin-1 ligand transforms CpG into a multitask nanoparticulate TLR9 agonist (Ken ISHII in PNAS)

CpG oligonucleotide (ODN), a synthetic TLR9 ligand, is a promising immunotherapeutic agent; however, it has not been successful to develop interferon (IFN)-inducing CpG ODN forming a stable nano-particle without undesirable aggregation.

The authors generated a nano size particle CpG ODN (K3) wrapped by a non-agonistic Dectin-1 ligand schzophyllan (SPG), namely K3-SPG. K3-SPG stimulates human PBMCs to produce a large amount of both type-I and type-II IFN without losing IL-6 production ability. K3-SPG thus became a potent adjuvant, especially for CTL induction to co-administered protein antigens without conjugation that is attributed to its nature of nano-particle, rather than targeting Dectin-1. In addition, most of K3-SPG was rapidly trapped by MARCO+ macrophages in the draining lymph node, and then K3-SPG activated pDCs and CD8 + DCs to exert its adjuvant effects. K3-SPG acted as an influenza vaccine adjuvant was demonstrated in vivo by both murine and non-human primate model. Taken together, K3-SPG may be used as IFN-inducer as well as CTL inducer for immunotherapeutic applications.



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Contact:

Ken ISHII
Vaccine Science
Immunology Frontier Research Center (WPI-IFReC), Osaka University

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