Molecular determinants of human neutralizing antibodies isolated from a patient infected with Zika virus

Qihui Wang; Huabing Yang; Xiaoqing Liu; Lianpan Dai; Tong Ma; Jianxun Qi; Gary Wong; Ruchao Peng; Sheng Liu; Junfu Li; Shihua Li; Jian Song; Jianying Liu; Jianhua He; Hui Yuan; Ying Xiong; Yong Liao; Jianhua Li; Jianping Yang; Zhou Tong; Bryan D. Griffin; Yuhai Bi; Mifang Liang; Xiaoning Xu; Chuan Qin; Gong Cheng; Xinzheng Zhang; Peiyi Wang; Xiangguo Qiu; Gary Kobinger; Yi Shi; Jinghua Yan; George F. Gao

doi:10.1126/scitranslmed.aai8336

Molecular determinants of human neutralizing antibodies isolated from a patient infected with Zika virus

Qihui Wang, Huabing Yang, Xiaoqing Liu, Lianpan Dai, Tong Ma, Jianxun Qi, Gary Wong, Ruchao Peng, Sheng Liu, Junfu Li, Shihua Li, Jian Song, Jianying Liu, Jianhua He, Hui Yuan, Ying Xiong, Yong Liao, Jianhua Li, Jianping Yang, Zhou TongBryan D. Griffin, Yuhai Bi, Mifang Liang, Xiaoning Xu, Chuan Qin, Gong Cheng, Xinzheng Zhang, Peiyi Wang, Xiangguo Qiu, Gary Kobinger, Yi Shi, Jinghua Yan, George F. Gao

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Abstract

The 2015-2016 outbreak of Zika virus (ZIKV) disease has affected many countries and is a major public health concern. ZIKV is associated with fetal microcephaly and neurological complications, and countermeasures are needed to treat and prevent ZIKV infection. We report the isolation of 13 specific human monoclonal antibodies from a single patient infected with ZIKV. Two of the isolated antibodies (Z23 and Z3L1) demonstrated potent ZIKV-specific neutralization in vitro without binding or neutralizing activity against strains 1 to 4 of dengue virus, the closest relative to ZIKV. These two antibodies provided postexposure protection to mice in vivo. Structural studies revealed that Z23 and Z3L1 bound to tertiary epitopes in envelope protein domain I, II, or III, indicating potential targets for ZIKV-specific therapy. Our results suggest the potential of antibody-based therapeutics and provide a structure-based rationale for the design of future ZIKV-specific vaccines.

Original language	English (US)
Article number	369ra179
Journal	Science Translational Medicine
Volume	8
Issue number	369
DOIs	https://doi.org/10.1126/scitranslmed.aai8336
State	Published - Dec 14 2016
Externally published	Yes

ASJC Scopus subject areas

General Medicine

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10.1126/scitranslmed.aai8336

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Wang, Q., Yang, H., Liu, X., Dai, L., Ma, T., Qi, J., Wong, G., Peng, R., Liu, S., Li, J., Li, S., Song, J., Liu, J., He, J., Yuan, H., Xiong, Y., Liao, Y., Li, J., Yang, J., ... Gao, G. F. (2016). Molecular determinants of human neutralizing antibodies isolated from a patient infected with Zika virus. Science Translational Medicine, 8(369), Article 369ra179. https://doi.org/10.1126/scitranslmed.aai8336

Wang, Q, Yang, H, Liu, X, Dai, L, Ma, T, Qi, J, Wong, G, Peng, R, Liu, S, Li, J, Li, S, Song, J, Liu, J, He, J, Yuan, H, Xiong, Y, Liao, Y, Li, J, Yang, J, Tong, Z, Griffin, BD, Bi, Y, Liang, M, Xu, X, Qin, C, Cheng, G, Zhang, X, Wang, P, Qiu, X, Kobinger, G, Shi, Y, Yan, J & Gao, GF 2016, 'Molecular determinants of human neutralizing antibodies isolated from a patient infected with Zika virus', Science Translational Medicine, vol. 8, no. 369, 369ra179. https://doi.org/10.1126/scitranslmed.aai8336

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abstract = "The 2015-2016 outbreak of Zika virus (ZIKV) disease has affected many countries and is a major public health concern. ZIKV is associated with fetal microcephaly and neurological complications, and countermeasures are needed to treat and prevent ZIKV infection. We report the isolation of 13 specific human monoclonal antibodies from a single patient infected with ZIKV. Two of the isolated antibodies (Z23 and Z3L1) demonstrated potent ZIKV-specific neutralization in vitro without binding or neutralizing activity against strains 1 to 4 of dengue virus, the closest relative to ZIKV. These two antibodies provided postexposure protection to mice in vivo. Structural studies revealed that Z23 and Z3L1 bound to tertiary epitopes in envelope protein domain I, II, or III, indicating potential targets for ZIKV-specific therapy. Our results suggest the potential of antibody-based therapeutics and provide a structure-based rationale for the design of future ZIKV-specific vaccines.",

author = "Qihui Wang and Huabing Yang and Xiaoqing Liu and Lianpan Dai and Tong Ma and Jianxun Qi and Gary Wong and Ruchao Peng and Sheng Liu and Junfu Li and Shihua Li and Jian Song and Jianying Liu and Jianhua He and Hui Yuan and Ying Xiong and Yong Liao and Jianhua Li and Jianping Yang and Zhou Tong and Griffin, {Bryan D.} and Yuhai Bi and Mifang Liang and Xiaoning Xu and Chuan Qin and Gong Cheng and Xinzheng Zhang and Peiyi Wang and Xiangguo Qiu and Gary Kobinger and Yi Shi and Jinghua Yan and Gao, {George F.}",

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AU - Wang, Qihui

AU - Yang, Huabing

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AU - Dai, Lianpan

AU - Ma, Tong

AU - Qi, Jianxun

AU - Wong, Gary

AU - Peng, Ruchao

AU - Liu, Sheng

AU - Li, Junfu

AU - Li, Shihua

AU - Song, Jian

AU - Liu, Jianying

AU - He, Jianhua

AU - Yuan, Hui

AU - Xiong, Ying

AU - Liao, Yong

AU - Li, Jianhua

AU - Yang, Jianping

AU - Tong, Zhou

AU - Griffin, Bryan D.

AU - Bi, Yuhai

AU - Liang, Mifang

AU - Xu, Xiaoning

AU - Qin, Chuan

AU - Cheng, Gong

AU - Zhang, Xinzheng

AU - Wang, Peiyi

AU - Qiu, Xiangguo

AU - Kobinger, Gary

AU - Shi, Yi

AU - Yan, Jinghua

AU - Gao, George F.

PY - 2016/12/14

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N2 - The 2015-2016 outbreak of Zika virus (ZIKV) disease has affected many countries and is a major public health concern. ZIKV is associated with fetal microcephaly and neurological complications, and countermeasures are needed to treat and prevent ZIKV infection. We report the isolation of 13 specific human monoclonal antibodies from a single patient infected with ZIKV. Two of the isolated antibodies (Z23 and Z3L1) demonstrated potent ZIKV-specific neutralization in vitro without binding or neutralizing activity against strains 1 to 4 of dengue virus, the closest relative to ZIKV. These two antibodies provided postexposure protection to mice in vivo. Structural studies revealed that Z23 and Z3L1 bound to tertiary epitopes in envelope protein domain I, II, or III, indicating potential targets for ZIKV-specific therapy. Our results suggest the potential of antibody-based therapeutics and provide a structure-based rationale for the design of future ZIKV-specific vaccines.

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Molecular determinants of human neutralizing antibodies isolated from a patient infected with Zika virus

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