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

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  • Dan Li
    Peking University-Tsinghua University-National Institute of Biological Sciences Joint Graduate Program, School of Life Sciences, Tsinghua University, Beijing, China
  • Wenhui He
    National Institute of Biological Sciences, Beijing, China
  • Ximing Liu
    National Institute of Biological Sciences, 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
  • 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
  • Kaixin Du
    National Institute of Biological Sciences, Beijing, China
  • Keqiong Ye
    National Institute of Biological Sciences, Beijing, China
  • Wenhui Li
    National Institute of Biological Sciences, Beijing, China
  • Jianhua Sui
    National Institute of Biological Sciences, Beijing, China

Description

<jats:p>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.</jats:p>

Journal

  • eLife

    eLife 6 2017-09-26

    eLife Sciences Publications, Ltd

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