Human antibodies to the dengue virus E-dimer epitope have therapeutic activity against Zika virus infection

Fernandez Estefania; Dejnirattisai Wanwisa; Cao Bin; Scheaffer Suzanne M.; Supasa Piyada; Wongwiwat Wiyada; Esakky Prabagaran; Drury Andrea; Mongkolsapaya Juthathip; Moley Kelle H.; Mysorekar Indira U.; Screaton Gavin R.; Diamond Michael S.

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Human antibodies to the dengue virus E-dimer epitope have therapeutic activity against Zika virus infection

机译：登革热病毒E-Dimer表位的人抗体对Zika病毒感染具有治疗活动

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The Zika virus (ZIKV) epidemic has resulted in congenital abnormalities in fetuses and neonates. Although some cross-reactive dengue virus (DENV)-specific antibodies can enhance ZIKV infection in mice, those recognizing the DENV E-dimer epitope (EDE) can neutralize ZIKV infection in cell culture. We evaluated the therapeutic activity of human monoclonal antibodies to DENV EDE for their ability to control ZIKV infection in the brains, testes, placentas, and fetuses of mice. A single dose of the EDE1-B10 antibody given 3 d after ZIKV infection protected against lethality, reduced ZIKV levels in brains and testes, and preserved sperm counts. In pregnant mice, wild-type or engineered LALA variants of EDE1-B10, which cannot engage Fc gamma receptors, diminished ZIKV burden in maternal and fetal tissues, and protected against fetal demise. Because neutralizing antibodies to EDE have therapeutic potential against ZIKV, in addition to their established inhibitory effects against DENV, it may be possible to develop therapies that control disease caused by both viruses.

机译：Zika病毒（ZIKV）流行病导致胎儿和新生儿的先天性异常。虽然一些交叉反应性登革热病毒（DENV）的特异性抗体可以增强小鼠中的ZIKV感染，但识别丹佛E-DIMER表位（EDE）的那些可以中和细胞培养中的ZIKV感染。我们评估了人单克隆抗体对Denv EDE的治疗活性，以便他们在大脑中控制ZIKV感染的能力，睾丸，胎盘和小鼠胎儿中的能力。在ZIKV感染后，单剂量的EDE1-B10抗体受到抗杀伤症的影响，患有硫化态，降低ZIKV水平和睾丸，并保存精子计数。在怀孕的小鼠，野生型或工程化LALA变体的EDE1-B10，不能接触Fcγ受体，减少母亲和胎儿组织中的Zikv负担，并防止胎儿消亡。由于对EDE的抗体的抗体具有免受ZIKV的治疗潜力，除了它们对DENV的鉴定抑制作用之外，还可以开发治疗两种病毒引起的疾病的疗法。

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《Nature immunology》 |2017年第11期|共9页
作者
Fernandez Estefania; Dejnirattisai Wanwisa; Cao Bin; Scheaffer Suzanne M.; Supasa Piyada; Wongwiwat Wiyada; Esakky Prabagaran; Drury Andrea; Mongkolsapaya Juthathip; Moley Kelle H.; Mysorekar Indira U.; Screaton Gavin R.; Diamond Michael S.;
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作者单位

Washington Univ Sch Med Dept Pathol &

Immunol St Louis MO 63110 USA;

Imperial Coll Dept Med Div Immunol &

Inflammat Hammersmith Campus London England;

Washington Univ Sch Med Dept Obstet &

Gynecol St Louis MO 63110 USA;

Washington Univ Sch Med Dept Obstet &

Gynecol St Louis MO 63110 USA;

Imperial Coll Dept Med Div Immunol &

Inflammat Hammersmith Campus London England;

Imperial Coll Dept Med Div Immunol &

Inflammat Hammersmith Campus London England;

Washington Univ Sch Med Dept Obstet &

Gynecol St Louis MO 63110 USA;

Washington Univ Sch Med Dept Obstet &

Gynecol St Louis MO 63110 USA;

Imperial Coll Dept Med Div Immunol &

Inflammat Hammersmith Campus London England;

Washington Univ Sch Med Dept Obstet &

Gynecol St Louis MO 63110 USA;

Washington Univ Sch Med Dept Pathol &

Immunol St Louis MO 63110 USA;

Imperial Coll Dept Med Div Immunol &

Inflammat Hammersmith Campus London England;

Washington Univ Sch Med Dept Pathol &

Immunol St Louis MO 63110 USA;

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正文语种 eng
中图分类医学免疫学;
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专利

1. Author Correction: Human antibodies to the dengue virus E-dimer epitope have therapeutic activity against Zika virus infection. [J] . Nature immunology . 2020,第3期

机译：作者校正：人类抗体对登革热病毒E二聚体表位具有针对Zika病毒感染的治疗活动。
2. Human Serum With High Neutralizing Antibody Titers Against Both Zika and Dengue Virus Shows Delayed In Vitro Antibody-Dependent Enhancement of Dengue Virus Infection [J] . William G Valiant, Tahaniyat Lalani, Heather C Yun, Open Forum Infectious Diseases . 2018,第7期

机译：对寨卡病毒和登革热病毒均具有高中和抗体滴度的人血清显示延迟的抗体依赖性登革热病毒感染的体外增强
3. Nonstructural protein 1 antibody-based epitope-blocking enzyme-linked immunosorbent assay to differentiate Japanese encephalitis virus from dengue virus infections in humans. [J] . Konishi E, Konishi M Japanese journal of infectious diseases . 2011,第4期

机译：基于非结构蛋白1抗体的表位封闭酶联免疫吸附测定法，用于区分人中的日本脑炎病毒和登革热病毒感染。
4. IMPLEMENTATION OF A STRATEGY TO PRODUCE A BROADLY NEUTRALIZING MONOCLONAL ANTIBODY AGAINST ZIKA AND DENGUE VIRUSES [C] . Esmeralda Cuevas-Juarez, Laura A. Palomares Conference on vaccine technology VI . 2018

机译：实施针对寨卡病毒和登革热病毒的广泛中和性单克隆抗体的策略的实施
5. The Roles of Virus-Host Interactions in the Pathogenesis of Dengue and Zika Viral Infections [D] . Robinson, Makeda Lucretia. 2020

机译：病毒 - 宿主相互作用在登革热和ZIKA病毒感染的发病机制中的作用
6. Anti-Dengue E-dimer epitope human antibodies have therapeutic activity against Zika virus infection [O] . Estefania Fernandez, Wanwisa Dejnirattisai, Bin Cao, -1

机译：抗登革热E-二聚体表位人类抗体具有抵抗寨卡病毒感染的治疗活性
7. Human antibodies to the dengue virus E-dimer epitope have therapeutic activity against Zika virus infection. [O] . Fernandez, E, Dejnirattisai, W, Cao, B, 2017

机译：登革热病毒E-二聚体表位的人抗体具有针对寨卡病毒感染的治疗活性。
8. Infection Enhancement of Dengue Type 2 Virus in the U-937 Human Monocyte Cell Line by Antibodies to Flavivirus Cross-Reactive Determinants [R] . Brandt, W. E., McCown, J. M., Gentry, M. K., 1981

机译：黄病毒交叉反应决定因子抗体对U-937人单核细胞系登革2型病毒的感染增强作用

Human antibodies to the dengue virus E-dimer epitope have therapeutic activity against Zika virus infection

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