Bepirovirsen induces innate immune activation in the liver potentially through TLR8 signaling

Key Points

• The aim is to explore how bepirovirsen activates the innate immune system in addition to its antiviral effects.
• Analyzed cytokine production in Phase 2a serum and plasma samples.
• Conducted preclinical studies using PBMCs and PRR-overexpressing cells.
• Measured cytokine levels in hTLR8 transgenic mice and assessed gene expression through RT-qPCR.
• Pro-inflammatory cytokines were significantly upregulated in bepirovirsen-treated participants.
• Innate immune activation occurred only in cells with human TLR8 (p=0.00085).
• In hTLR8 mice, bepirovirsen treatment increased inflammatory cytokines, similar to TLR8 agonist effects.