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Antibodies targeting epitopes on the cell-surface form of NS1 protect against Zika virus infection during pregnancy
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Antibodies targeting epitopes on the cell-surface form of NS1 protect against Zika virus infection during pregnancy
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Journal Article
Antibodies targeting epitopes on the cell-surface form of NS1 protect against Zika virus infection during pregnancy
2020
Overview
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.
Zika virus is an arthropod-transmitted flavivirus that can cause microcephaly and other fetal abnormalities during pregnancy. Here Wessel et al. develop antibodies against the Zika virus nonstructural protein 1 that protect non-pregnant and pregnant mice against infection, and define particular antibody epitopes and mechanisms underlying this protection.
Publisher
Nature Publishing Group UK,Nature Portfolio
Subject
/ 13/109
/ 64
/ 64/60
/ 82/47
/ Animals
/ Antibodies, Viral - administration & dosage
/ Antibodies, Viral - immunology
/ Antibody-Dependent Enhancement
/ Female
/ Humanities and Social Sciences
/ Humans
/ Male
/ Mice
/ Pregnancy Complications, Infectious - immunology
/ Pregnancy Complications, Infectious - prevention & control
/ Pregnancy Complications, Infectious - virology
/ Science
/ Viral Nonstructural Proteins - chemistry
/ Viral Nonstructural Proteins - genetics
/ Viral Nonstructural Proteins - immunology
/ Zika Virus Infection - congenital
/ Zika Virus Infection - immunology
