Monoclonal antibodies targeting HBsAg as anti-HDV: clinical prospects

Hepatitis D (delta) virus (HDV) remains the most severe form of chronic viral hepatitis and represents a substantial global health burden. Although effective prophylactic vaccines against hepatitis B virus (HBV) indirectly prevent HDV infection, an estimated 12 million people worldwide remain chronically infected with HDV. Current antiviral strategies suppress viral replication but rarely achieve sustained virological response or functional cure, resulting in lifelong treatment for many patients. As HDV depends on hepatitis B surface antigen (HBsAg) for virion assembly and entry into hepatocytes, targeting the viral envelope represents an attractive therapeutic strategy to prevent viral spread. Advances in recombinant antibody engineering have enabled the development of highly potent human monoclonal antibodies (mAbs) against viral pathogens, including HBV and HDV. Neutralizing anti-HBsAg mAbs block viral entry by binding HBsAg and preventing its interaction with the receptor, while their Fc domains may additionally promote immune-mediated clearance of viral particles and infected cells. Compared with conventional small-molecule antivirals, mAbs generally exhibit high target specificity and favorable safety profiles, thus making them promising candidates for antiviral therapy Currently, one mAb has been licensed in China for the treatment of adults with chronic HDV, with or without compensated cirrhosis, while several additional neutralizing mAbs are being evaluated in preclinical and clinical studies as monotherapy or in combination with other antiviral agents. This review summarizes the current landscape of monoclonal antibody development for chronic HDV infection, highlighting their mechanisms of action, preclinical and clinical efficacy, and potential role in future therapeutic strategies.