Species‐dependent role of type I IFNs and IL‐12 in the CTL response induced by humanized CpG complexed with β‐glucan

Abstract

CpG oligodeoxynucleotide (ODN) is one of promising nucleic acid-based adjuvants. We recently improved its ability to enhance CD8

Induction of humoural and cellular immunity by immunisation with HCV particle vaccine in a non-human primate model

“…The induction of IFN-γ mRNA expression by stimulation with a nearly full-length HCV core protein was only observed in the marmosets immunised with the preparation containing K3-SPG. Thus, we concluded that K3-SPG contributed to the induction of cellular immunity in addition to humoural immunity 15 16. The induction of cellular immunity was more pronounced in the animals that were vaccinate three times compared with those that were vaccinated twice.…”

An Antigen-Free, Plasmacytoid Dendritic Cell–Targeting Immunotherapy To Bolster Memory CD8+ T Cells in Nonhuman Primates

“…K3-SPG is a nanoparticulate CpG ODN wrapped in the nonagonistic Dectin-1 ligand, SPG. K3-SPG should be superior to the current K3 CpG DNA, which is under clinical development (38), in terms of its ability to induce type I IFN production, and its adjuvant and monoimmunotherapeutic activities against cancer (19)(20)(21). However, discrepancies in the expression of PRRs, including TLR9, between mice and humans or NHPs limit the translation of any findings into clinical use (39).…”

“…Previously, we reported that K3-SPG can induce potent CTL responses and anticancer effects without Ag in mice (19)(20)(21); however, the effects of K3-SPG on the immune system of NHPs remain unknown. To confirm the potency of K3-SPG in NHPs, we first verified the activation of total memory CD8 + T cells by a single injection of 2 mg of K3, K3-SPG, or poly(I:C) in vivo (Fig.…”

“…K3-SPG induces the robust production of type I and type II IFN and Th1 type cytokines in human PBMCs and acts as a strong adjuvant for influenza split vaccine in mice and nonhuman primates (NHPs) to elicit Ag-specific Abs (19). K3-SPG can also stimulate strong Ag-specific CTL responses and induce the extensive production of anticancer cytokines, such as type I IFN and IL-12, to function as an anticancer monotherapy agent in mice (20,21). However, type I IFN, but not IL-12, is required for IFN-g production by human PBMCs and for the proliferation of CMV-specific CD8 + T cells in vitro (20).…”

“…K3-SPG can also stimulate strong Ag-specific CTL responses and induce the extensive production of anticancer cytokines, such as type I IFN and IL-12, to function as an anticancer monotherapy agent in mice (20,21). However, type I IFN, but not IL-12, is required for IFN-g production by human PBMCs and for the proliferation of CMV-specific CD8 + T cells in vitro (20). Nevertheless, it remains unclear whether humanized CpG DNA molecules can induce IL-12 or what the effect of IL-12 on optimal CTL responses might be in vivo.…”