Peking University-Tsinghua University-National Institute of Biological Sciences Joint Graduate Program, School of Life Sciences, Tsinghua University, Beijing, China; National Institute of Biological Sciences, Beijing, China
Wenhui He
National Institute of Biological Sciences, Beijing, China
Ximing Liu
National Institute of Biological Sciences, Beijing, China; PTN Joint Graduate Program, College of Life Sciences, Peking University, Beijing, China
Sanduo Zheng
National Institute of Biological Sciences, Beijing, China
Yonghe Qi
National Institute of Biological Sciences, Beijing, China
Huiyu Li
National Institute of Biological Sciences, Beijing, China
Fengfeng Mao
National Institute of Biological Sciences, Beijing, China; Graduate Program in College of Life Sciences, Beijing Normal University, Beijing, China
Juan Liu
National Institute of Biological Sciences, Beijing, China
Yinyan Sun
National Institute of Biological Sciences, Beijing, China
Lijing Pan
Peking University-Tsinghua University-National Institute of Biological Sciences Joint Graduate Program, School of Life Sciences, Tsinghua University, Beijing, China; National Institute of Biological Sciences, Beijing, China
Kaixin Du
National Institute of Biological Sciences, Beijing, China; Graduate Program in College of Life Sciences, Beijing Normal University, Beijing, China
Hepatitis B virus (HBV) infection is a major global health problem. Currently-available therapies are ineffective in curing chronic HBV infection. HBV and its satellite hepatitis D virus (HDV) infect hepatocytes via binding of the preS1 domain of its large envelope protein to sodium taurocholate cotransporting polypeptide (NTCP). Here, we developed novel human monoclonal antibodies that block the engagement of preS1 with NTCP and neutralize HBV and HDV with high potency. One antibody, 2H5-A14, functions at picomolar level and exhibited neutralization-activity-mediated prophylactic effects. It also acts therapeutically by eliciting antibody-Fc-dependent immunological effector functions that impose durable suppression of viral infection in HBV-infected mice, resulting in reductions in the levels of the small envelope antigen and viral DNA, with no emergence of escape mutants. Our results illustrate a novel antibody-Fc-dependent approach for HBV treatment and suggest 2H5-A14 as a novel clinical candidate for HBV prevention and treatment of chronic HBV infection.
