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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.
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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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