A potent human neutralizing antibody Fc-dependently reduces established HBV infections
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 cot...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2017-09-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/26738 |
| _version_ | 1818018888831467520 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Dan Li |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-14T07:45:38Z |
| format | Article |
| id | doaj.art-eb2d66a881064cf38d0fb7b25eca3db5 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-14T07:45:38Z |
| publishDate | 2017-09-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-eb2d66a881064cf38d0fb7b25eca3db52022-12-22T02:05:22ZengeLife Sciences Publications LtdeLife2050-084X2017-09-01610.7554/eLife.26738A potent human neutralizing antibody Fc-dependently reduces established HBV infectionsDan Li0https://orcid.org/0000-0002-3670-4056Wenhui He1Ximing Liu2Sanduo Zheng3Yonghe Qi4Huiyu Li5Fengfeng Mao6Juan Liu7Yinyan Sun8Lijing Pan9Kaixin Du10Keqiong Ye11https://orcid.org/0000-0001-6169-7049Wenhui Li12https://orcid.org/0000-0003-1305-7404Jianhua Sui13https://orcid.org/0000-0002-1272-9662Peking 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, ChinaNational Institute of Biological Sciences, Beijing, ChinaNational Institute of Biological Sciences, Beijing, China; PTN Joint Graduate Program, College of Life Sciences, Peking University, Beijing, ChinaNational Institute of Biological Sciences, Beijing, ChinaNational Institute of Biological Sciences, Beijing, ChinaNational Institute of Biological Sciences, Beijing, ChinaNational Institute of Biological Sciences, Beijing, China; Graduate Program in College of Life Sciences, Beijing Normal University, Beijing, ChinaNational Institute of Biological Sciences, Beijing, ChinaNational Institute of Biological Sciences, Beijing, ChinaPeking 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, ChinaNational Institute of Biological Sciences, Beijing, China; Graduate Program in College of Life Sciences, Beijing Normal University, Beijing, ChinaNational Institute of Biological Sciences, Beijing, ChinaNational Institute of Biological Sciences, Beijing, ChinaNational Institute of Biological Sciences, Beijing, ChinaHepatitis 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.https://elifesciences.org/articles/26738HBVNTCPpreS1antibodyFc receptoreffector function |
| spellingShingle | 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 A potent human neutralizing antibody Fc-dependently reduces established HBV infections eLife HBV NTCP preS1 antibody Fc receptor effector function |
| title | A potent human neutralizing antibody Fc-dependently reduces established HBV infections |
| title_full | A potent human neutralizing antibody Fc-dependently reduces established HBV infections |
| title_fullStr | A potent human neutralizing antibody Fc-dependently reduces established HBV infections |
| title_full_unstemmed | A potent human neutralizing antibody Fc-dependently reduces established HBV infections |
| title_short | A potent human neutralizing antibody Fc-dependently reduces established HBV infections |
| title_sort | potent human neutralizing antibody fc dependently reduces established hbv infections |
| topic | HBV NTCP preS1 antibody Fc receptor effector function |
| url | https://elifesciences.org/articles/26738 |
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