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 and Michael S. Diamond ()
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Alex W. Wessel: Washington University School of Medicine
Nurgun Kose: Vanderbilt University Medical Center
Robin G. Bombardi: Vanderbilt University Medical Center
Vicky Roy: Ragon Institute of MGH, MIT, and Harvard University
Warangkana Chantima: University of Oxford
Juthathip Mongkolsapaya: University of Oxford
Melissa A. Edeling: Washington University School of Medicine
Christopher A. Nelson: Washington University School of Medicine
Irene Bosch: E25Bio, Inc., The Engine of MIT
Galit Alter: Ragon Institute of MGH, MIT, and Harvard University
Gavin R. Screaton: University of Oxford
David H. Fremont: Washington University School of Medicine
James E. Crowe: Vanderbilt University Medical Center
Michael S. Diamond: Washington University School of Medicine

Nature Communications, 2020, vol. 11, issue 1, 1-13

Abstract: Abstract 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.

Date: 2020
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DOI: 10.1038/s41467-020-19096-y

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