Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/90226
Title: Cross-reactive dengue human monoclonal antibody prevents severe pathologies and death from Zika virus infections
Authors: Kam, Yiu-Wing
Lee, Cheryl Yi-Pin
Teo, Teck-Hui
Howland, Shanshan W.
Siti Naqiah Amrun
Lum, Fok-Moon
See, Peter
Kng, Nicholas Qing-Rong
Huber, Roland G.
Xu, Mei-Hui
Tan, Heng-Liang
Choo, Andre
Maurer-Stroh, Sebastian
Ginhoux, Florent
Fink, Katja
Wang, Cheng-I
Ng, Lisa F.P.
Rénia, Laurent
Keywords: Zika Virus
Monoclonal Antibody
DRNTU::Science::Biological sciences
Issue Date: 2017
Source: Kam, Y.-W., Lee, C. Y.-P., Teo, T.-H., Howland, S. W., Siti Naqiah Amrun, Lum, F.-M., See, P., et al. (2017). Cross-reactive dengue human monoclonal antibody prevents severe pathologies and death from Zika virus infections. JCI Insight, 2(8), e92428. doi:10.1172/jci.insight.92428.
Series/Report no.: JCI Insight
Abstract: Zika virus (ZIKV) infections have been linked with neurological complications and congenital Zika syndrome. Given the high level of homology between ZIKV and the related flavivirus dengue virus (DENV), we investigated the level of cross-reactivity with ZIKV using a panel of DENV human mAbs. A majority of the mAbs showed binding to ZIKV virions, with several exhibiting neutralizing capacities against ZIKV in vitro. Three of the best ZIKV-neutralizing mAbs were found to recognize diverse epitopes on the envelope (E) glycoprotein: the highly conserved fusion-loop peptide, a conformation-specific epitope on the E monomer, and a quaternary epitope on the virion surface. The most potent ZIKV-neutralizing mAb (SIgN-3C) was assessed in 2 type I interferon receptor–deficient (IFNAR–/–) mouse models of ZIKV infection. Treatment of adult nonpregnant mice with SIgN-3C rescued mice from virus-induced weight loss and mortality. The SIgN-3C variant with Leu-to-Ala mutations in the Fc region (SIgN-3C-LALA) did not induce antibody-dependent enhancement (ADE) in vitro but provided similar levels of protection in vivo. In pregnant ZIKV-infected IFNAR–/– mice, treatment with SIgN-3C or SIgN-3C-LALA significantly reduced viral load in the fetal organs and placenta and abrogated virus-induced fetal growth retardation. Therefore, SIgN-3C-LALA holds promise as a ZIKV prophylactic and therapeutic agent.
URI: https://hdl.handle.net/10356/90226
http://hdl.handle.net/10220/47229
DOI: http://dx.doi.org/10.1172/jci.insight.92428
Rights: © 2017 American Society for Clinical Investigation (ASCI). This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:SBS Journal Articles

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