TY - JOUR T1 - Novel prime-boost immune-based therapy inhibiting both hepatitis B and D virus infections JF - Gut JO - Gut DO - 10.1136/gutjnl-2022-327216 SP - gutjnl-2022-327216 AU - Rani Burm AU - Panagiota Maravelia AU - Gustaf Ahlen AU - Sandra Ciesek AU - Noelia Caro Perez AU - Anna Pasetto AU - Stephan Urban AU - Freya Van Houtte AU - Lieven Verhoye AU - Heiner Wedemeyer AU - Magnus Johansson AU - Lars Frelin AU - Matti Sällberg AU - Philip Meuleman Y1 - 2022/08/17 UR - http://gut.bmj.com/content/early/2022/09/01/gutjnl-2022-327216.abstract N2 - Objective Chronic HBV/HDV infections are a major cause of liver cancer. Current treatments can only rarely eliminate HBV and HDV. Our previously developed preS1-HDAg immunotherapy could induce neutralising antibodies to HBV in vivo and raise HBV/HDV-specific T-cells. Here, we further investigate if a heterologous prime-boost strategy can circumvent T-cell tolerance and preclude HDV superinfection in vivo.Design A DNA prime-protein boost strategy was evaluated for immunogenicity in mice and rabbits. Its ability to circumvent T-cell tolerance was assessed in immunocompetent hepatitis B surface antigen (HBsAg)-transgenic mice. Neutralisation of HBV and HDV was evaluated both in vitro and in immunodeficient human-liver chimeric mice upon adoptive transfer.Results The prime-boost strategy elicits robust HBV/HDV-specific T-cells and preS1-antibodies that can effectively prevent HBV and HDV (co-)infection in vitro and in vivo. In a mouse model representing the chronic HBsAg carrier state, active immunisation primes high levels of preS1-antibodies and HDAg-specific T-cells. Moreover, transfer of vaccine-induced antibodies completely protects HBV-infected human-liver chimeric mice from HDV superinfection.Conclusion The herein described preS1-HDAg immunotherapy is shown to be immunogenic and vaccine-induced antibodies are highly effective at preventing HBV and HDV (super)infection both in vitro and in vivo. Our vaccine can complement current and future therapies for the control of chronic HBV and HDV infection.All data relevant to the study are included in the article or uploaded as supplementary information. ER -