一种靶向融合前蛋白保守区域的单克隆抗体可交叉中和尼帕病毒和亨德拉病毒变体

IF 4 2区医学 Q1 PHARMACOLOGY & PHARMACY

Antiviral research Pub Date : 2025-06-18 DOI:10.1016/j.antiviral.2025.106215

Tao Li , Hua Xu , Mengyi Zhang , Jianhui Nie , Binfan Liao , Jingshu Xie , Yinan Jiang , Yawen Liu , Pingju Ge , Chunhui Zhao , Ziqi Sun , Yunbo Bai , Maoling Tang , Xiaodong Su , Youchun Wang , Weijin Huang

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引用次数: 0

摘要

尼帕病毒（NiV）和亨德拉病毒（HeV）具有极高的病死率，在全球几个国家导致数百人死亡。同属Henipavirus (HNV)，两种病毒序列高度相似，在有利条件下产生交叉中和免疫。本研究利用杂杂瘤技术获得了10种抗NiV- f单克隆抗体，并通过假病毒实验验证了这些抗体对来自不同地区的流行性NiV株具有较强的中和活性，中和浓度达到纳克/毫升水平。此外，两种抗体NiF03-3C9和NiF03-2F6对HeV具有交叉中和活性，其交叉中和活性甚至强于对NiV的交叉中和活性。表位竞争分析显示这些抗体具有两类表位。低温电镜显示，NiF03-3C9与预融合F蛋白三聚体的侧残基结合，在尼帕病毒和亨德拉病毒中高度保守。利用尼帕病毒和亨德拉病毒的体内假病毒感染模型也验证了抗体的保护效力。本研究开发的单抗及其经结构分析确定的保守交叉中和表位可能有助于控制高致病性HNV暴发。

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A monoclonal antibody targeting conserved regions of pre-fusion protein cross-neutralizes Nipah and Hendra virus variants

Nipah virus (NiV) and Hendra virus (HeV) have an extremely high case fatality, leading to hundreds of deaths in several countries around the globe. Belonging to the same genus Henipavirus (HNV), the two species have a high degree of sequence similarity, resulting in cross-neutralizing immunity under favorable conditions. Here, we obtained ten anti-NiV-F monoclonal antibodies using hybridoma technology, and verified that these antibodies had potent neutralizing activities against epidemic NiV strains from different regions using a pseudovirus assay, and the neutralizing concentration reached the nanogram per milliliter level. Moreover, two of the antibodies, NiF03-3C9 and NiF03-2F6, were found to have cross-neutralizing activity against HeV, which was even stronger than that against NiV. Epitope competition analysis revealed two classes of epitopes for these antibodies. Cryo-electron microscopy showed that NiF03-3C9 binds to lateral residues of the prefusion F protein trimer, highly conserved in both Nipah and Hendra. The protective potency of the antibodies was also validated using in vivo pseudovirus infection models of Nipah and Hendra viruses. The mAbs developed in this study and their conserved cross-neutralizing epitopes elucidated by structural analysis may contribute to the control of highly pathogenic HNV outbreaks.

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来源期刊

Antiviral research 医学-病毒学

CiteScore

17.10

自引率

3.90%

发文量

157

审稿时长

34 days

期刊介绍： Antiviral Research is a journal that focuses on various aspects of controlling viral infections in both humans and animals. It is a platform for publishing research reports, short communications, review articles, and commentaries. The journal covers a wide range of topics including antiviral drugs, antibodies, and host-response modifiers. These topics encompass their synthesis, in vitro and in vivo testing, as well as mechanisms of action. Additionally, the journal also publishes studies on the development of new or improved vaccines against viral infections in humans. It delves into assessing the safety of drugs and vaccines, tracking the evolution of drug or vaccine-resistant viruses, and developing effective countermeasures. Another area of interest includes the identification and validation of new drug targets. The journal further explores laboratory animal models of viral diseases, investigates the pathogenesis of viral diseases, and examines the mechanisms by which viruses avoid host immune responses.