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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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 |
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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 |
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© 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. |
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Vanderbilt University Medical Center |
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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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1763488548051222528 |