Zika-specific neutralizing antibodies targeting inter-dimer envelope epitopes
Summary: Zika virus (ZIKV) is an emerging pathogen that causes devastating congenital defects. The overlapping epidemiology and immunologic cross-reactivity between ZIKV and dengue virus (DENV) pose complex challenges to vaccine design, given the potential for antibody-dependent enhancement of disea...
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Format: | Article |
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Elsevier
2023-08-01
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Series: | Cell Reports |
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Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124723009531 |
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author | Rajeshwer S. Sankhala Vincent Dussupt Gina Donofrio Gregory D. Gromowski Rafael A. De La Barrera Rafael A. Larocca Letzibeth Mendez-Rivera Anna Lee Misook Choe Weam Zaky Grace Mantus Jaime L. Jensen Wei-Hung Chen Neelakshi Gohain Hongjun Bai Michael K. McCracken Rosemarie D. Mason David Leggat Bonnie M. Slike Ursula Tran Ningbo Jian Peter Abbink Rebecca Peterson Eric Araujo Mendes Rafael Freitas de Oliveira Franca Guilherme Amaral Calvet Ana Maria Bispo de Filippis Adrian McDermott Mario Roederer Mayda Hernandez Amie Albertus Edgar Davidson Benjamin J. Doranz Morgane Rolland Merlin L. Robb Rebecca M. Lynch Dan H. Barouch Richard G. Jarman Stephen J. Thomas Kayvon Modjarrad Nelson L. Michael Shelly J. Krebs M. Gordon Joyce |
author_facet | Rajeshwer S. Sankhala Vincent Dussupt Gina Donofrio Gregory D. Gromowski Rafael A. De La Barrera Rafael A. Larocca Letzibeth Mendez-Rivera Anna Lee Misook Choe Weam Zaky Grace Mantus Jaime L. Jensen Wei-Hung Chen Neelakshi Gohain Hongjun Bai Michael K. McCracken Rosemarie D. Mason David Leggat Bonnie M. Slike Ursula Tran Ningbo Jian Peter Abbink Rebecca Peterson Eric Araujo Mendes Rafael Freitas de Oliveira Franca Guilherme Amaral Calvet Ana Maria Bispo de Filippis Adrian McDermott Mario Roederer Mayda Hernandez Amie Albertus Edgar Davidson Benjamin J. Doranz Morgane Rolland Merlin L. Robb Rebecca M. Lynch Dan H. Barouch Richard G. Jarman Stephen J. Thomas Kayvon Modjarrad Nelson L. Michael Shelly J. Krebs M. Gordon Joyce |
author_sort | Rajeshwer S. Sankhala |
collection | DOAJ |
description | Summary: Zika virus (ZIKV) is an emerging pathogen that causes devastating congenital defects. The overlapping epidemiology and immunologic cross-reactivity between ZIKV and dengue virus (DENV) pose complex challenges to vaccine design, given the potential for antibody-dependent enhancement of disease. Therefore, classification of ZIKV-specific antibody targets is of notable value. From a ZIKV-infected rhesus macaque, we identify ZIKV-reactive B cells and isolate potent neutralizing monoclonal antibodies (mAbs) with no cross-reactivity to DENV. We group these mAbs into four distinct antigenic groups targeting ZIKV-specific cross-protomer epitopes on the envelope glycoprotein. Co-crystal structures of representative mAbs in complex with ZIKV envelope glycoprotein reveal envelope-dimer epitope and unique dimer-dimer epitope targeting. All four specificities are serologically identified in convalescent humans following ZIKV infection, and representative mAbs from all four groups protect against ZIKV replication in mice. These results provide key insights into ZIKV-specific antigenicity and have implications for ZIKV vaccine, diagnostic, and therapeutic development. |
first_indexed | 2024-03-12T11:54:09Z |
format | Article |
id | doaj.art-df7415563897410eaec20a0810786ea8 |
institution | Directory Open Access Journal |
issn | 2211-1247 |
language | English |
last_indexed | 2024-03-12T11:54:09Z |
publishDate | 2023-08-01 |
publisher | Elsevier |
record_format | Article |
series | Cell Reports |
spelling | doaj.art-df7415563897410eaec20a0810786ea82023-08-31T05:02:16ZengElsevierCell Reports2211-12472023-08-01428112942Zika-specific neutralizing antibodies targeting inter-dimer envelope epitopesRajeshwer S. Sankhala0Vincent Dussupt1Gina Donofrio2Gregory D. Gromowski3Rafael A. De La Barrera4Rafael A. Larocca5Letzibeth Mendez-Rivera6Anna Lee7Misook Choe8Weam Zaky9Grace Mantus10Jaime L. Jensen11Wei-Hung Chen12Neelakshi Gohain13Hongjun Bai14Michael K. McCracken15Rosemarie D. Mason16David Leggat17Bonnie M. Slike18Ursula Tran19Ningbo Jian20Peter Abbink21Rebecca Peterson22Eric Araujo Mendes23Rafael Freitas de Oliveira Franca24Guilherme Amaral Calvet25Ana Maria Bispo de Filippis26Adrian McDermott27Mario Roederer28Mayda Hernandez29Amie Albertus30Edgar Davidson31Benjamin J. Doranz32Morgane Rolland33Merlin L. Robb34Rebecca M. Lynch35Dan H. Barouch36Richard G. Jarman37Stephen J. Thomas38Kayvon Modjarrad39Nelson L. Michael40Shelly J. Krebs41M. Gordon Joyce42Emerging Infectious Disease Branch, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD, USAEmerging Infectious Disease Branch, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD, USA; U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USAEmerging Infectious Disease Branch, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD, USA; U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USAViral Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USAPilot Bioproduction Facility, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USACenter for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USAEmerging Infectious Disease Branch, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD, USA; U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USAHenry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD, USA; U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USAEmerging Infectious Disease Branch, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD, USAHenry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD, USA; U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USAGeorge Washington University School of Medicine & Health Sciences, Washington, DC, USAEmerging Infectious Disease Branch, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD, USAEmerging Infectious Disease Branch, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD, USAEmerging Infectious Disease Branch, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD, USAHenry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD, USA; U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USAViral Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USAVaccine Research Center, NIH, Bethesda, MD 20852, USAVaccine Research Center, NIH, Bethesda, MD 20852, USAHenry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD, USA; U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USAHenry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD, USA; U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USAHenry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD, USA; U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USACenter for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USACenter for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USACenter for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USAOswaldo Cruz Foundation Institute Aggeu Magalhães, Recife, PE 50740-465, BrazilOswaldo Cruz Foundation, Evandro Chagas National Institute of Infectious Diseases, Rio de Janeiro, RJ 21040-360, BrazilOswaldo Cruz Foundation, Oswaldo Cruz Institute, Rio de Janeiro, RJ 21041-300, BrazilVaccine Research Center, NIH, Bethesda, MD 20852, USAVaccine Research Center, NIH, Bethesda, MD 20852, USAIntegral Molecular, Philadelphia, PA 19104, USAIntegral Molecular, Philadelphia, PA 19104, USAIntegral Molecular, Philadelphia, PA 19104, USAIntegral Molecular, Philadelphia, PA 19104, USAHenry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD, USA; U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USAHenry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD, USAGeorge Washington University School of Medicine & Health Sciences, Washington, DC, USACenter for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USAViral Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USAViral Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USAEmerging Infectious Disease Branch, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USACenter of Infectious Disease Research, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USAEmerging Infectious Disease Branch, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD, USA; U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA; Corresponding authorEmerging Infectious Disease Branch, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD, USA; U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA; Corresponding authorSummary: Zika virus (ZIKV) is an emerging pathogen that causes devastating congenital defects. The overlapping epidemiology and immunologic cross-reactivity between ZIKV and dengue virus (DENV) pose complex challenges to vaccine design, given the potential for antibody-dependent enhancement of disease. Therefore, classification of ZIKV-specific antibody targets is of notable value. From a ZIKV-infected rhesus macaque, we identify ZIKV-reactive B cells and isolate potent neutralizing monoclonal antibodies (mAbs) with no cross-reactivity to DENV. We group these mAbs into four distinct antigenic groups targeting ZIKV-specific cross-protomer epitopes on the envelope glycoprotein. Co-crystal structures of representative mAbs in complex with ZIKV envelope glycoprotein reveal envelope-dimer epitope and unique dimer-dimer epitope targeting. All four specificities are serologically identified in convalescent humans following ZIKV infection, and representative mAbs from all four groups protect against ZIKV replication in mice. These results provide key insights into ZIKV-specific antigenicity and have implications for ZIKV vaccine, diagnostic, and therapeutic development.http://www.sciencedirect.com/science/article/pii/S2211124723009531CP: Immunology |
spellingShingle | Rajeshwer S. Sankhala Vincent Dussupt Gina Donofrio Gregory D. Gromowski Rafael A. De La Barrera Rafael A. Larocca Letzibeth Mendez-Rivera Anna Lee Misook Choe Weam Zaky Grace Mantus Jaime L. Jensen Wei-Hung Chen Neelakshi Gohain Hongjun Bai Michael K. McCracken Rosemarie D. Mason David Leggat Bonnie M. Slike Ursula Tran Ningbo Jian Peter Abbink Rebecca Peterson Eric Araujo Mendes Rafael Freitas de Oliveira Franca Guilherme Amaral Calvet Ana Maria Bispo de Filippis Adrian McDermott Mario Roederer Mayda Hernandez Amie Albertus Edgar Davidson Benjamin J. Doranz Morgane Rolland Merlin L. Robb Rebecca M. Lynch Dan H. Barouch Richard G. Jarman Stephen J. Thomas Kayvon Modjarrad Nelson L. Michael Shelly J. Krebs M. Gordon Joyce Zika-specific neutralizing antibodies targeting inter-dimer envelope epitopes Cell Reports CP: Immunology |
title | Zika-specific neutralizing antibodies targeting inter-dimer envelope epitopes |
title_full | Zika-specific neutralizing antibodies targeting inter-dimer envelope epitopes |
title_fullStr | Zika-specific neutralizing antibodies targeting inter-dimer envelope epitopes |
title_full_unstemmed | Zika-specific neutralizing antibodies targeting inter-dimer envelope epitopes |
title_short | Zika-specific neutralizing antibodies targeting inter-dimer envelope epitopes |
title_sort | zika specific neutralizing antibodies targeting inter dimer envelope epitopes |
topic | CP: Immunology |
url | http://www.sciencedirect.com/science/article/pii/S2211124723009531 |
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