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
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- Wenhui He
- National Institute of Biological Sciences, Beijing, China
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- Ximing Liu
- National Institute of Biological Sciences, Beijing, China
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- Sanduo Zheng
- National Institute of Biological Sciences, Beijing, China
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- Yonghe Qi
- National Institute of Biological Sciences, Beijing, China
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- Huiyu Li
- National Institute of Biological Sciences, Beijing, China
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- Fengfeng Mao
- National Institute of Biological Sciences, Beijing, China
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- Juan Liu
- National Institute of Biological Sciences, Beijing, China
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- Yinyan Sun
- National Institute of Biological Sciences, Beijing, China
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- Lijing Pan
- Peking University-Tsinghua University-National Institute of Biological Sciences Joint Graduate Program, School of Life Sciences, Tsinghua University, Beijing, China
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- Kaixin Du
- National Institute of Biological Sciences, Beijing, China
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- Keqiong Ye
- National Institute of Biological Sciences, Beijing, China
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- Wenhui Li
- National Institute of Biological Sciences, Beijing, China
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- Jianhua Sui
- National Institute of Biological Sciences, Beijing, China
説明
<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>
収録刊行物
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- eLife
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eLife 6 2017-09-26
eLife Sciences Publications, Ltd