Antibodies targeting epitopes on the cell-surface form of NS1 protect against Zika virus infection during pregnancy

© 2020, The Author(s). There are no licensed therapeutics or vaccines available against Zika virus (ZIKV) to counteract its potential for congenital disease. Antibody-based countermeasures targeting the ZIKV envelope protein have been hampered by concerns for cross-reactive responses that induce ant...

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Main Authors: Alex W. Wessel, Nurgun Kose, Robin G. Bombardi, Vicky Roy, Warangkana Chantima, Juthathip Mongkolsapaya, Melissa A. Edeling, Christopher A. Nelson, Irene Bosch, Galit Alter, Gavin R. Screaton, David H. Fremont, James E. Crowe, Michael S. Diamond
Other Authors: Vanderbilt University Medical Center
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Published: 2020
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Online Access:https://repository.li.mahidol.ac.th/handle/123456789/59851
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spelling th-mahidol.598512020-11-18T15:37:43Z Antibodies targeting epitopes on the cell-surface form of NS1 protect against Zika virus infection during pregnancy Alex W. Wessel Nurgun Kose Robin G. Bombardi Vicky Roy Warangkana Chantima Juthathip Mongkolsapaya Melissa A. Edeling Christopher A. Nelson Irene Bosch Galit Alter Gavin R. Screaton David H. Fremont James E. Crowe Michael S. Diamond Vanderbilt University Medical Center Washington University School of Medicine in St. Louis Massachusetts Institute of Technology Faculty of Medicine, Siriraj Hospital, Mahidol University Harvard University Nuffield Department of Medicine Biochemistry, Genetics and Molecular Biology Chemistry © 2020, The Author(s). There are no licensed therapeutics or vaccines available against Zika virus (ZIKV) to counteract its potential for congenital disease. Antibody-based countermeasures targeting the ZIKV envelope protein have been hampered by concerns for cross-reactive responses that induce antibody-dependent enhancement (ADE) of heterologous flavivirus infection. Nonstructural protein 1 (NS1) is a membrane-associated and secreted glycoprotein that functions in flavivirus replication and immune evasion but is absent from the virion. Although some studies suggest that antibodies against ZIKV NS1 are protective, their activity during congenital infection is unknown. Here we develop mouse and human anti-NS1 monoclonal antibodies that protect against ZIKV in both non-pregnant and pregnant mice. Avidity of antibody binding to cell-surface NS1 along with Fc effector functions engagement correlate with protection in vivo. Protective mAbs map to exposed epitopes in the wing domain and loop face of the β-platform. Anti-NS1 antibodies provide an alternative strategy for protection against congenital ZIKV infection without causing ADE. 2020-11-18T07:59:15Z 2020-11-18T07:59:15Z 2020-12-01 Article Nature Communications. Vol.11, No.1 (2020) 10.1038/s41467-020-19096-y 20411723 2-s2.0-85092785339 https://repository.li.mahidol.ac.th/handle/123456789/59851 Mahidol University SCOPUS https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85092785339&origin=inward
institution Mahidol University
building Mahidol University Library
continent Asia
country Thailand
Thailand
content_provider Mahidol University Library
collection Mahidol University Institutional Repository
topic Biochemistry, Genetics and Molecular Biology
Chemistry
spellingShingle Biochemistry, Genetics and Molecular Biology
Chemistry
Alex W. Wessel
Nurgun Kose
Robin G. Bombardi
Vicky Roy
Warangkana Chantima
Juthathip Mongkolsapaya
Melissa A. Edeling
Christopher A. Nelson
Irene Bosch
Galit Alter
Gavin R. Screaton
David H. Fremont
James E. Crowe
Michael S. Diamond
Antibodies targeting epitopes on the cell-surface form of NS1 protect against Zika virus infection during pregnancy
description © 2020, The Author(s). There are no licensed therapeutics or vaccines available against Zika virus (ZIKV) to counteract its potential for congenital disease. Antibody-based countermeasures targeting the ZIKV envelope protein have been hampered by concerns for cross-reactive responses that induce antibody-dependent enhancement (ADE) of heterologous flavivirus infection. Nonstructural protein 1 (NS1) is a membrane-associated and secreted glycoprotein that functions in flavivirus replication and immune evasion but is absent from the virion. Although some studies suggest that antibodies against ZIKV NS1 are protective, their activity during congenital infection is unknown. Here we develop mouse and human anti-NS1 monoclonal antibodies that protect against ZIKV in both non-pregnant and pregnant mice. Avidity of antibody binding to cell-surface NS1 along with Fc effector functions engagement correlate with protection in vivo. Protective mAbs map to exposed epitopes in the wing domain and loop face of the β-platform. Anti-NS1 antibodies provide an alternative strategy for protection against congenital ZIKV infection without causing ADE.
author2 Vanderbilt University Medical Center
author_facet Vanderbilt University Medical Center
Alex W. Wessel
Nurgun Kose
Robin G. Bombardi
Vicky Roy
Warangkana Chantima
Juthathip Mongkolsapaya
Melissa A. Edeling
Christopher A. Nelson
Irene Bosch
Galit Alter
Gavin R. Screaton
David H. Fremont
James E. Crowe
Michael S. Diamond
format Article
author Alex W. Wessel
Nurgun Kose
Robin G. Bombardi
Vicky Roy
Warangkana Chantima
Juthathip Mongkolsapaya
Melissa A. Edeling
Christopher A. Nelson
Irene Bosch
Galit Alter
Gavin R. Screaton
David H. Fremont
James E. Crowe
Michael S. Diamond
author_sort Alex W. Wessel
title Antibodies targeting epitopes on the cell-surface form of NS1 protect against Zika virus infection during pregnancy
title_short Antibodies targeting epitopes on the cell-surface form of NS1 protect against Zika virus infection during pregnancy
title_full Antibodies targeting epitopes on the cell-surface form of NS1 protect against Zika virus infection during pregnancy
title_fullStr Antibodies targeting epitopes on the cell-surface form of NS1 protect against Zika virus infection during pregnancy
title_full_unstemmed Antibodies targeting epitopes on the cell-surface form of NS1 protect against Zika virus infection during pregnancy
title_sort antibodies targeting epitopes on the cell-surface form of ns1 protect against zika virus infection during pregnancy
publishDate 2020
url https://repository.li.mahidol.ac.th/handle/123456789/59851
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