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TLR7-8 RNA ligands

Vaxjo ID 247       
Vaccine Adjuvant Name TLR7-8 RNA ligands       
Adjuvant VO ID VO_0005734
Description Synthetic single-stranded RNA molecules designed to activate TLR7 and TLR8 in immune cells, promoting innate immune responses and co-stimulation of γδ T cells       
Stage of Development Research       
Components Here we have used recently described RNA ligands for TLR7 and TLR8 together with V纬9V未2 T-cell specific pyrophosphate antigens to analyze the rapid cytokine induction in V未2 T cells as well as the accessory cell requirements. While TLR8- as well as TLR7/8-specific RNA did not induce IFN-纬 in V未2 T cells on their own, they provided strong co-stimulation for V未2 T cells within peripheral blood mononuclear cells in the presence of additional T-cell receptor activation. In contrast, TLR7 ligands were ineffective.       
Structure Short synthetic single-stranded RNA oligonucleotides, complexed with poly-arginine (pArg) for delivery       
Preparation Short synthetic single-stranded RNA oligonucleotides, complexed with poly-arginine (pArg) for delivery       
Dosage ssRNA40: 2 µg/mL R2152 & 9.2s: 4 µg/mL Optimal concentrations determined via titration for PBMC activation       
Function Toll-like receptors (TLR) are pattern recognition receptors in innate immune cells which sense microbial structures including nucleic acids       
Safety No adverse effects reported in vitro; well-tolerated in PBMC culture models       
References
Serrano et al., 2021: Serrano R, Coch C, Peters C, Hartmann G, Wesch D, Kabelitz D. Monocyte-dependent co-stimulation of cytokine induction in human γδ T cells by TLR8 RNA ligands. Scientific reports. 2021; 11(1); 15231. [PubMed: 34315922].