猕猴体内强效中和寨卡病毒单克隆抗体的保护阈值。

IF 4 2区 医学 Q2 VIROLOGY
Journal of Virology Pub Date : 2024-12-17 Epub Date: 2024-11-15 DOI:10.1128/jvi.01429-24
Joseph P Nkolola, David Hope, Ruoran Guan, Alessandro Colarusso, Malika Aid, Deborah Weiss, John Misamore, Hanne Andersen, Mark G Lewis, Lauren Williamson, Robert H Carnahan, James E Crowe, Dan H Barouch
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引用次数: 0

摘要

寨卡病毒(ZIKV)是一种由蚊子传播的黄病毒,曾在 2016-2017 年引发全球大流行,并在多个国家持续低水平传播。在没有获得批准的寨卡病毒疫苗的情况下,中和单克隆抗体(mAbs)为预防和治疗寨卡病毒感染提供了一种选择。之前的研究发现了一种强效中和性人类 mAb ZIKV-117,它能减少小鼠在受到 ZIKV 挑战后的胎儿感染和死亡。在本研究中,我们报告了 ZIKV-117-LALA-YTE 在恒河猴滴定研究中的卓越功效,该抗体经过设计,可减少 Fc 受体结合并延长半衰期,从而抵御 ZIKV 挑战。我们的研究结果表明,ZIKV-117-LALA-YTE 的剂量为 0.016 mg/kg,血清浓度中值为 0.13 µg/mL,即可提供完全保护。重要意义在这项研究中,我们报告了寨卡病毒(ZIKV)特异性中和抗体 ZIKV-117-LALA-YTE 在猕猴滴定研究中抵御 ZIKV 挑战的效力。这种高效力支持进一步开发这种针对 ZIKV 的单克隆抗体。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Protective threshold of a potent neutralizing Zika virus monoclonal antibody in rhesus macaques.

Zika virus (ZIKV) is a mosquito-borne flavivirus that caused a global pandemic in 2016-2017 with continued ongoing transmission at low levels in several countries. In the absence of an approved ZIKV vaccine, neutralizing monoclonal antibodies (mAbs) provide an option for the prevention and treatment of ZIKV infection. Previous studies identified a potent neutralizing human mAb ZIKV-117 that reduced fetal infection and death in mice following ZIKV challenge. In this study, we report exquisite potency of ZIKV-117-LALA-YTE, which has been engineered to reduce Fc receptor binding and to extend half-life, in a titration study in rhesus macaques to protect against ZIKV challenge. We show complete protection at a dose of 0.016 mg/kg ZIKV-117-LALA-YTE, which resulted in median serum concentrations of 0.13 µg/mL. The high potency of this mAb supports its potential clinical development as a novel biotherapeutic intervention for ZIKV.IMPORTANCEIn this study, we report the potency of the Zika virus (ZIKV)-specific neutralizing antibody ZIKV-117-LALA-YTE against ZIKV challenge in a titration study rhesus macaques. This high potency supports the further development of this monoclonal antibody for ZIKV.

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来源期刊
Journal of Virology
Journal of Virology 医学-病毒学
CiteScore
10.10
自引率
7.40%
发文量
906
审稿时长
1 months
期刊介绍: Journal of Virology (JVI) explores the nature of the viruses of animals, archaea, bacteria, fungi, plants, and protozoa. We welcome papers on virion structure and assembly, viral genome replication and regulation of gene expression, genetic diversity and evolution, virus-cell interactions, cellular responses to infection, transformation and oncogenesis, gene delivery, viral pathogenesis and immunity, and vaccines and antiviral agents.
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