Neutralization of Zika virus by germline-like human monoclonal antibodies targeting cryptic epitopes on envelope domain III
The Zika virus (ZIKV), a flavivirus transmitted by Aedes mosquitoes, has emerged as a global public health concern. Pre-existing cross-reactive antibodies against other flaviviruses could modulate immune responses to ZIKV infection by antibody-dependent enhancement, highlighting the importance of un...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2017-01-01
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| Series: | Emerging Microbes and Infections |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1038/emi.2017.79 |
| _version_ | 1797676933004132352 |
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| author | Yanling Wu Shun Li Lanying Du Chunyu Wang Peng Zou Binbin Hong Mengjiao Yuan Xiaonan Ren Wanbo Tai Yu Kong Chen Zhou Lu Lu Xiaohui Zhou Shibo Jiang Tianlei Ying |
| author_facet | Yanling Wu Shun Li Lanying Du Chunyu Wang Peng Zou Binbin Hong Mengjiao Yuan Xiaonan Ren Wanbo Tai Yu Kong Chen Zhou Lu Lu Xiaohui Zhou Shibo Jiang Tianlei Ying |
| author_sort | Yanling Wu |
| collection | DOAJ |
| description | The Zika virus (ZIKV), a flavivirus transmitted by Aedes mosquitoes, has emerged as a global public health concern. Pre-existing cross-reactive antibodies against other flaviviruses could modulate immune responses to ZIKV infection by antibody-dependent enhancement, highlighting the importance of understanding the immunogenicity of the ZIKV envelope protein. In this study, we identified a panel of human monoclonal antibodies (mAbs) that target domain III (DIII) of the ZIKV envelope protein from a very large phage-display naive antibody library. These germline-like antibodies, sharing 98%–100% hoLogy with their corresponding germline IGHV genes, bound ZIKV DIII specifically with high affinities. One mAb, m301, broadly neutralized the currently circulating ZIKV strains and showed a synergistic effect with another mAb, m302, in neutralizing ZIKV in vitro and in a mouse model of ZIKV infection. Interestingly, epitope mapping and competitive binding studies suggest that m301 and m302 bind adjacent regions of the DIII C–C′ loop, which represents a recently identified cryptic epitope that is intermittently exposed in an uncharacterized virus conformation. This study extended our understanding of antigenic epitopes of ZIKV antibodies and has direct implications for the design of ZIKV vaccines.Emerging Microbes & Infections (2017) 6, e89; doi:10.1038/emi.2017.79; published online 11 October 2017 |
| first_indexed | 2024-03-11T22:37:36Z |
| format | Article |
| id | doaj.art-1b21717166d24c6086f59d7d20833335 |
| institution | Directory Open Access Journal |
| issn | 2222-1751 |
| language | English |
| last_indexed | 2024-03-11T22:37:36Z |
| publishDate | 2017-01-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Emerging Microbes and Infections |
| spelling | doaj.art-1b21717166d24c6086f59d7d208333352023-09-22T12:08:35ZengTaylor & Francis GroupEmerging Microbes and Infections2222-17512017-01-016111110.1038/emi.2017.79Neutralization of Zika virus by germline-like human monoclonal antibodies targeting cryptic epitopes on envelope domain IIIYanling Wu0Shun Li1Lanying Du2Chunyu Wang3Peng Zou4Binbin Hong5Mengjiao Yuan6Xiaonan Ren7Wanbo Tai8Yu Kong9Chen Zhou10Lu Lu11Xiaohui Zhou12Shibo Jiang13Tianlei Ying14Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, School of Basic Medical SciencesFudan University, Shanghai 200032, ChinaShanghai Public Health Clinical CenterFudan University, Shanghai 201508, ChinaLindsley F Kimball Research Institute, New York Blood Center, New York, NY 10065, USAKey Laboratory of Medical Molecular Virology of Ministries of Education and Health, School of Basic Medical SciencesFudan University, Shanghai 200032, ChinaShanghai Public Health Clinical CenterFudan University, Shanghai 201508, ChinaKey Laboratory of Medical Molecular Virology of Ministries of Education and Health, School of Basic Medical SciencesFudan University, Shanghai 200032, ChinaShanghai Public Health Clinical CenterFudan University, Shanghai 201508, ChinaShanghai Public Health Clinical CenterFudan University, Shanghai 201508, ChinaLindsley F Kimball Research Institute, New York Blood Center, New York, NY 10065, USAKey Laboratory of Medical Molecular Virology of Ministries of Education and Health, School of Basic Medical SciencesFudan University, Shanghai 200032, ChinaBiomissile Corporation, Shanghai 201203, ChinaKey Laboratory of Medical Molecular Virology of Ministries of Education and Health, School of Basic Medical SciencesFudan University, Shanghai 200032, ChinaShanghai Public Health Clinical CenterFudan University, Shanghai 201508, ChinaKey Laboratory of Medical Molecular Virology of Ministries of Education and Health, School of Basic Medical SciencesFudan University, Shanghai 200032, ChinaKey Laboratory of Medical Molecular Virology of Ministries of Education and Health, School of Basic Medical SciencesFudan University, Shanghai 200032, ChinaThe Zika virus (ZIKV), a flavivirus transmitted by Aedes mosquitoes, has emerged as a global public health concern. Pre-existing cross-reactive antibodies against other flaviviruses could modulate immune responses to ZIKV infection by antibody-dependent enhancement, highlighting the importance of understanding the immunogenicity of the ZIKV envelope protein. In this study, we identified a panel of human monoclonal antibodies (mAbs) that target domain III (DIII) of the ZIKV envelope protein from a very large phage-display naive antibody library. These germline-like antibodies, sharing 98%–100% hoLogy with their corresponding germline IGHV genes, bound ZIKV DIII specifically with high affinities. One mAb, m301, broadly neutralized the currently circulating ZIKV strains and showed a synergistic effect with another mAb, m302, in neutralizing ZIKV in vitro and in a mouse model of ZIKV infection. Interestingly, epitope mapping and competitive binding studies suggest that m301 and m302 bind adjacent regions of the DIII C–C′ loop, which represents a recently identified cryptic epitope that is intermittently exposed in an uncharacterized virus conformation. This study extended our understanding of antigenic epitopes of ZIKV antibodies and has direct implications for the design of ZIKV vaccines.Emerging Microbes & Infections (2017) 6, e89; doi:10.1038/emi.2017.79; published online 11 October 2017https://www.tandfonline.com/doi/10.1038/emi.2017.79cryptic epitopehuman monoclonal antibodiesZika virus |
| spellingShingle | Yanling Wu Shun Li Lanying Du Chunyu Wang Peng Zou Binbin Hong Mengjiao Yuan Xiaonan Ren Wanbo Tai Yu Kong Chen Zhou Lu Lu Xiaohui Zhou Shibo Jiang Tianlei Ying Neutralization of Zika virus by germline-like human monoclonal antibodies targeting cryptic epitopes on envelope domain III Emerging Microbes and Infections cryptic epitope human monoclonal antibodies Zika virus |
| title | Neutralization of Zika virus by germline-like human monoclonal antibodies targeting cryptic epitopes on envelope domain III |
| title_full | Neutralization of Zika virus by germline-like human monoclonal antibodies targeting cryptic epitopes on envelope domain III |
| title_fullStr | Neutralization of Zika virus by germline-like human monoclonal antibodies targeting cryptic epitopes on envelope domain III |
| title_full_unstemmed | Neutralization of Zika virus by germline-like human monoclonal antibodies targeting cryptic epitopes on envelope domain III |
| title_short | Neutralization of Zika virus by germline-like human monoclonal antibodies targeting cryptic epitopes on envelope domain III |
| title_sort | neutralization of zika virus by germline like human monoclonal antibodies targeting cryptic epitopes on envelope domain iii |
| topic | cryptic epitope human monoclonal antibodies Zika virus |
| url | https://www.tandfonline.com/doi/10.1038/emi.2017.79 |
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