A new class of highly potent, broadly neutralizing antibodies isolated from viremic patients infected with dengue virus

Wanwisa Dejnirattisai; Wiyada Wongwiwat; Sunpetchuda Supasa; Xiaokang Zhang; Xinghong Dai; Alexander Rouvinski; Amonrat Jumnainsong; Carolyn Edwards; Nguyen Than Ha Quyen; Thaneeya Duangchinda; Jonathan M Grimes; Wen-Yang Tsai; Chih-Yun Lai; Wei-Kung Wang; Prida Malasit; Jeremy Farrar; Cameron P Simmons; Z Hong Zhou; Felix A Rey; Juthathip Mongkolsapaya; Gavin R Screaton

doi:10.1038/ni.3058

A new class of highly potent, broadly neutralizing antibodies isolated from viremic patients infected with dengue virus

Wanwisa Dejnirattisai, Wiyada Wongwiwat, Sunpetchuda Supasa, Xiaokang Zhang, Xinghong Dai, Alexander Rouvinski, Amonrat Jumnainsong, Carolyn Edwards, Nguyen Than Ha Quyen, Thaneeya Duangchinda, Jonathan M Grimes, Wen-Yang Tsai, Chih-Yun Lai, Wei-Kung Wang, Prida Malasit, Jeremy Farrar, Cameron P Simmons, Z Hong Zhou, Felix A Rey, Juthathip MongkolsapayaGavin R Screaton

Department of Microbiology and Molecular Genetics

Research output: Contribution to journal › Article › peer-review

337 Scopus citations

Abstract

Dengue is a rapidly emerging, mosquito-borne viral infection, with an estimated 400 million infections occurring annually. To gain insight into dengue immunity, we characterized 145 human monoclonal antibodies (mAbs) and identified a previously unknown epitope, the envelope dimer epitope (EDE), that bridges two envelope protein subunits that make up the 90 repeating dimers on the mature virion. The mAbs to EDE were broadly reactive across the dengue serocomplex and fully neutralized virus produced in either insect cells or primary human cells, with 50% neutralization in the low picomolar range. Our results provide a path to a subunit vaccine against dengue virus and have implications for the design and monitoring of future vaccine trials in which the induction of antibody to the EDE should be prioritized.

Original language	American English
Pages (from-to)	170-177
Number of pages	8
Journal	Nature Immunology
Volume	16
Issue number	2
DOIs	https://doi.org/10.1038/ni.3058
State	Published - Feb 2015

Bibliographical note

Funding Information:
We thank the Armed Forces Research Institute of Medical Sciences of Thailand (AFRIMS), C. Puttikhunt (National Center for Genetic Engineering and Biotechnology, Thailand) and W. Kasinrerk (Chiang Mai University) for the mouse mAb 4G2 to DENV E protein and mAb 1H10 to DENV; E. Harris (University of California Berkeley School of Public Health) for mAb E1D8 to DENV NS3 protein; H. Wardemann (Max Planck Institute for Infection Biology) for expression vectors for IgG1 or immunoglobulin κ-chain or λ-chain; A Flanagan (University of Oxford) for recombinant soluble E protein; the staff at Oxford University Clinical Research Unit Viet Nam for sample collection; and N. Ferguson (Imperial College London) for statistical advice. We acknowledge the use of instruments at the Electron Imaging Center for Nanomachines, supported by University of California Los Angeles and the US National Institutes of Health (1S10OD018111 and NSF DBI-1338135). Supported by the Medical Research Council UK, the Wellcome Trust (G.R.S.), the National Institutes for Health Research Biomedical Research Centre, the US National Institutes of Health (GM071940 and AI094386), European Commission Seventh Framework Programme (FP7/2007-2013; DENFREE project, 282 378) and the Thailand Research Fund through the Royal Golden Jubilee Ph.D. Program (S.S. and J.M.).

Publisher Copyright:
© 2015 Nature America, Inc.

Keywords

Animals
Antibodies, Monoclonal/blood
Antibodies, Neutralizing/blood
Biological Assay
Cell Line
Dengue/blood
Dengue Virus/immunology
Enzyme-Linked Immunosorbent Assay
Humans
Immunoblotting
Viral Envelope Proteins/immunology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Dejnirattisai, W., Wongwiwat, W., Supasa, S., Zhang, X., Dai, X., Rouvinski, A., Jumnainsong, A., Edwards, C., Quyen, N. T. H., Duangchinda, T., Grimes, J. M., Tsai, W-Y., Lai, C-Y., Wang, W-K., Malasit, P., Farrar, J., Simmons, C. P., Zhou, Z. H., Rey, F. A., ... Screaton, G. R. (2015). A new class of highly potent, broadly neutralizing antibodies isolated from viremic patients infected with dengue virus. Nature Immunology, 16(2), 170-177. https://doi.org/10.1038/ni.3058

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abstract = "Dengue is a rapidly emerging, mosquito-borne viral infection, with an estimated 400 million infections occurring annually. To gain insight into dengue immunity, we characterized 145 human monoclonal antibodies (mAbs) and identified a previously unknown epitope, the envelope dimer epitope (EDE), that bridges two envelope protein subunits that make up the 90 repeating dimers on the mature virion. The mAbs to EDE were broadly reactive across the dengue serocomplex and fully neutralized virus produced in either insect cells or primary human cells, with 50% neutralization in the low picomolar range. Our results provide a path to a subunit vaccine against dengue virus and have implications for the design and monitoring of future vaccine trials in which the induction of antibody to the EDE should be prioritized.",

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author = "Wanwisa Dejnirattisai and Wiyada Wongwiwat and Sunpetchuda Supasa and Xiaokang Zhang and Xinghong Dai and Alexander Rouvinski and Amonrat Jumnainsong and Carolyn Edwards and Quyen, {Nguyen Than Ha} and Thaneeya Duangchinda and Grimes, {Jonathan M} and Wen-Yang Tsai and Chih-Yun Lai and Wei-Kung Wang and Prida Malasit and Jeremy Farrar and Simmons, {Cameron P} and Zhou, {Z Hong} and Rey, {Felix A} and Juthathip Mongkolsapaya and Screaton, {Gavin R}",

note = "Funding Information: We thank the Armed Forces Research Institute of Medical Sciences of Thailand (AFRIMS), C. Puttikhunt (National Center for Genetic Engineering and Biotechnology, Thailand) and W. Kasinrerk (Chiang Mai University) for the mouse mAb 4G2 to DENV E protein and mAb 1H10 to DENV; E. Harris (University of California Berkeley School of Public Health) for mAb E1D8 to DENV NS3 protein; H. Wardemann (Max Planck Institute for Infection Biology) for expression vectors for IgG1 or immunoglobulin κ-chain or λ-chain; A Flanagan (University of Oxford) for recombinant soluble E protein; the staff at Oxford University Clinical Research Unit Viet Nam for sample collection; and N. Ferguson (Imperial College London) for statistical advice. We acknowledge the use of instruments at the Electron Imaging Center for Nanomachines, supported by University of California Los Angeles and the US National Institutes of Health (1S10OD018111 and NSF DBI-1338135). Supported by the Medical Research Council UK, the Wellcome Trust (G.R.S.), the National Institutes for Health Research Biomedical Research Centre, the US National Institutes of Health (GM071940 and AI094386), European Commission Seventh Framework Programme (FP7/2007-2013; DENFREE project, 282 378) and the Thailand Research Fund through the Royal Golden Jubilee Ph.D. Program (S.S. and J.M.). Publisher Copyright: {\textcopyright} 2015 Nature America, Inc.",

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Dejnirattisai, W, Wongwiwat, W, Supasa, S, Zhang, X, Dai, X, Rouvinski, A, Jumnainsong, A, Edwards, C, Quyen, NTH, Duangchinda, T, Grimes, JM, Tsai, W-Y, Lai, C-Y, Wang, W-K, Malasit, P, Farrar, J, Simmons, CP, Zhou, ZH, Rey, FA, Mongkolsapaya, J & Screaton, GR 2015, 'A new class of highly potent, broadly neutralizing antibodies isolated from viremic patients infected with dengue virus', Nature Immunology, vol. 16, no. 2, pp. 170-177. https://doi.org/10.1038/ni.3058

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T1 - A new class of highly potent, broadly neutralizing antibodies isolated from viremic patients infected with dengue virus

AU - Dejnirattisai, Wanwisa

AU - Wongwiwat, Wiyada

AU - Supasa, Sunpetchuda

AU - Zhang, Xiaokang

AU - Dai, Xinghong

AU - Rouvinski, Alexander

AU - Jumnainsong, Amonrat

AU - Edwards, Carolyn

AU - Quyen, Nguyen Than Ha

AU - Duangchinda, Thaneeya

AU - Grimes, Jonathan M

AU - Tsai, Wen-Yang

AU - Lai, Chih-Yun

AU - Wang, Wei-Kung

AU - Malasit, Prida

AU - Farrar, Jeremy

AU - Simmons, Cameron P

AU - Zhou, Z Hong

AU - Rey, Felix A

AU - Mongkolsapaya, Juthathip

AU - Screaton, Gavin R

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KW - Animals

KW - Antibodies, Monoclonal/blood

KW - Antibodies, Neutralizing/blood

KW - Biological Assay

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KW - Enzyme-Linked Immunosorbent Assay

KW - Humans

KW - Immunoblotting

KW - Viral Envelope Proteins/immunology

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DO - 10.1038/ni.3058

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SN - 1529-2908

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EP - 177

JO - Nature Immunology

JF - Nature Immunology

IS - 2

ER -

A new class of highly potent, broadly neutralizing antibodies isolated from viremic patients infected with dengue virus

Abstract

Bibliographical note

Keywords

UN SDGs

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