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 Rouvinsky; 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 Rouvinsky, 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^*

^*Corresponding author for this work

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

370 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	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 - 16 Jan 2015
Externally published	Yes

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Publisher Copyright:
© 2015 Nature America, Inc.

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Dejnirattisai, W., Wongwiwat, W., Supasa, S., Zhang, X., Dai, X., Rouvinsky, 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.",

author = "Wanwisa Dejnirattisai and Wiyada Wongwiwat and Sunpetchuda Supasa and Xiaokang Zhang and Xinghong Dai and Alexander Rouvinsky and Amonrat Jumnainsong and Carolyn Edwards and Quyen, {Nguyen Than Ha} and Thaneeya Duangchinda and Grimes, {Jonathan M.} and Tsai, {Wen Yang} and Lai, {Chih Yun} and Wang, {Wei Kung} 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.}",

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Dejnirattisai, W, Wongwiwat, W, Supasa, S, Zhang, X, Dai, X, Rouvinsky, A, Jumnainsong, A, Edwards, C, Quyen, NTH, Duangchinda, T, Grimes, JM, Tsai, WY, Lai, CY, Wang, WK, 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 - Rouvinsky, 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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A new class of highly potent, broadly neutralizing antibodies isolated from viremic patients infected with dengue virus

Abstract

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