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Kam YW, Lee CY, Teo TH, et al. Cross-reactive dengue human monoclonal antibody prevents severe pathologies and death from Zika virus infections. JCI Insight. 2017;2(8)doi: 10.1172/jci.insight.92428.
Kam, Y. W., Lee, C. Y., Teo, T. H., Howland, S. W., Amrun, S. N., Lum, F. M., See, P., Kng, N. Q., Huber, R. G., Xu, M. H., Tan, H. L., Choo, A., Maurer-Stroh, S., Ginhoux, F., Fink, K., Wang, C. I., Ng, L. F., & Rénia, L. (2017). Cross-reactive dengue human monoclonal antibody prevents severe pathologies and death from Zika virus infections. JCI insight, 2(8), . https://doi.org/10.1172/jci.insight.92428
Kam, Yiu-Wing, et al. "Cross-reactive dengue human monoclonal antibody prevents severe pathologies and death from Zika virus infections." JCI insight vol. 2,8 (2017). doi: https://doi.org/10.1172/jci.insight.92428
Kam YW, Lee CY, Teo TH, Howland SW, Amrun SN, Lum FM, See P, Kng NQ, Huber RG, Xu MH, Tan HL, Choo A, Maurer-Stroh S, Ginhoux F, Fink K, Wang CI, Ng LF, Rénia L. Cross-reactive dengue human monoclonal antibody prevents severe pathologies and death from Zika virus infections. JCI Insight. 2017 Apr 20;2(8). doi: 10.1172/jci.insight.92428. eCollection 2017 Apr 20. PMID: 28422757; PMCID: PMC5396524.
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JCI Insight. 2017 Apr 20;2(8). doi: 10.1172/jci.insight.92428. eCollection 2017 Apr 20.

Cross-reactive dengue human monoclonal antibody prevents severe pathologies and death from Zika virus infections.

JCI insight

Yiu-Wing Kam, Cheryl Yi-Pin Lee, Teck-Hui Teo, Shanshan W Howland, Siti Naqiah Amrun, Fok-Moon Lum, Peter See, Nicholas Qing-Rong Kng, Roland G Huber, Mei-Hui Xu, Heng-Liang Tan, Andre Choo, Sebastian Maurer-Stroh, Florent Ginhoux, Katja Fink, Cheng-I Wang, Lisa Fp Ng, Laurent Rénia

Affiliations

  1. Singapore Immunology Network, Agency for Technology and Research (A*STAR), Biopolis, Singapore.
  2. NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore.
  3. Bioinformatics Institute.
  4. Bioprocessing Technology Institute, A*STAR, Biopolis, Singapore.
  5. Department of Biomedical Engineering, Faculty of Engineering, National University of Singapore, Singapore.
  6. School of Biological Sciences, Nanyang Technological University, Singapore.
  7. Department of Biological Sciences, National University of Singapore, Singapore.
  8. Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
  9. Institute of Infection and Global Health, University of Liverpool, United Kingdom.

PMID: 28422757 PMCID: PMC5396524 DOI: 10.1172/jci.insight.92428

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.

Keywords: Infectious disease

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