Antibodies to distinct epitopes on MPXV enveloped virion provide additive and complete protection

IF 16.4 1区医学 Q1 IMMUNOLOGY

Science Immunology Pub Date : 2026-10-30 DOI:10.1126/sciimmunol.aee7011

Ding Zhang, Raianna F. Fantin, Xueyong Zhu, Ziqi Feng, Seok-Chan Park, Gabriel Laghlali, Jordan J. Clark, Guilherme M. Nobrega, Angelica C. Kottkamp, Marie I. Samanovic, Mark J. Mulligan, Jean K. Lim, Michael Schotsaert, Meng Yuan, Camila H. Coelho, Ian A. Wilson

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引用次数: 0

Abstract

The continuing evolution of monkeypox virus (MPXV) clades capable of sustained human-to-human transmission poses an escalating global health risk, yet no effective therapy exists for poxvirus infection. Here, we investigate a panel of human monoclonal antibodies (mAbs), derived from an antibody library, which targets A35 and B6 antigens located on the extracellular enveloped virion (EV). Four high-affinity mAbs target the central groove of the A35 dimer, whereas one targets a previously unidentified epitope on the A35 protruding loop. Three other mAbs recognize distinct, previously unmapped epitopes on the multidomain B6 antigen. Those epitopes are conserved across most orthopoxviruses. A combination of an anti-A35 and an anti-B6 antibody provides additive and complete protection from both morbidity and mortality in a lethal VACV mouse model, challenging the previous assumption that targeting both the EV and mature virion (MV) forms is required for full protection. These studies uncover critical information for next-generation therapeutics and vaccines against emerging MPXV as well as other Orthopoxvirus threats.

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针对MPXV包膜病毒粒子上不同表位的抗体提供附加的和完全的保护

能够持续人际传播的猴痘病毒（MPXV）分支的不断进化构成了不断升级的全球健康风险，但目前还没有针对痘病毒感染的有效治疗方法。在这里，我们研究了一组来自抗体库的人单克隆抗体（mab），其靶向位于细胞外包膜病毒粒子（EV）上的A35和B6抗原。四种高亲和力单克隆抗体靶向A35二聚体的中心凹槽，而一种靶向A35突出环上先前未识别的表位。另外三种单克隆抗体识别不同的、先前未定位的多结构域B6抗原表位。这些表位在大多数正痘病毒中是保守的。抗a35和抗b6抗体的组合在致死性VACV小鼠模型中提供了附加的和完全的保护，防止发病率和死亡率，挑战了之前的假设，即同时针对EV和成熟病毒粒子（MV）形式才能提供全面保护。这些研究揭示了针对新出现的MPXV以及其他正痘病毒威胁的下一代治疗方法和疫苗的关键信息。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Science Immunology Immunology and Microbiology-Immunology

CiteScore

32.90

自引率

2.00%

发文量

183

期刊介绍： Science Immunology is a peer-reviewed journal that publishes original research articles in the field of immunology. The journal encourages the submission of research findings from all areas of immunology, including studies on innate and adaptive immunity, immune cell development and differentiation, immunogenomics, systems immunology, structural immunology, antigen presentation, immunometabolism, and mucosal immunology. Additionally, the journal covers research on immune contributions to health and disease, such as host defense, inflammation, cancer immunology, autoimmunity, allergy, transplantation, and immunodeficiency. Science Immunology maintains the same high-quality standard as other journals in the Science family and aims to facilitate understanding of the immune system by showcasing innovative advances in immunology research from all organisms and model systems, including humans.