A potent human neutralizing antibody Fc-dependently reduces established HBV infections

• DOI: 10.7554/elife.26738
• Publication Date: 2017-09-14T17:00:13Z
• Authors: Dan Li; Wenhui He; Ximing Liu; Sanduo Zheng; Yonghe Qi; Huiyu Li; Fengfeng Mao; Juan Liu; Yinyan Sun; Lijing Pan; Kaixin Du; Keqiong Ye; Wenhui Li; Jianhua Sui
• Keywords: 0301 basic medicine; Hepatitis B virus; QH301-705.5; Science; NTCP; Antibodies, Viral; Antiviral Agents; Chemoprevention; Mice; 03 medical and health sciences; Immunology and Inflammation; antibody; HBV; Animals; Humans; Biology (General); Q; R; Antibodies, Monoclonal; Hepatitis B; Antibodies, Neutralizing; 3. Good health; Disease Models, Animal; Treatment Outcome; Fc receptor; preS1; Medicine; Immunotherapy; Hepatitis Delta Virus; effector function

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.