Long-term Antigen Reduction is Insufficient to Cure Hepatitis B Virus in Mice

This study investigated whether prolonged suppression of HBV antigens could restore HBV-specific immune responses and support therapeutic vaccination. HBV-carrier mice were treated for up to eight months with liver-directed siRNAs or shRNAs targeting all HBV transcripts.

Although viral antigens declined initially, a threshold was reached after four months, and extended suppression alone did not restore T-cell immunity; viral replication rebounded after treatment stopped. However, combining antigen suppression with the therapeutic vaccine TherVacB reconstituted antiviral T-cell responses and achieved sustained HBV control. Longer siRNA pretreatment enhanced interferon signaling and improved vaccine-induced immunity, highlighting the need for combined antiviral suppression and immune stimulation.