DataSheet1_Characterization of a plant-derived monoclonal antibody targeting extracellular enveloped virions of Monkeypox virus.pdf

In 2022, the global outbreak of monkeypox virus (MPXV) with increased human-to-human transmission triggered urgent public health interventions. Plant-derived monoclonal antibodies (mAbs) are being explored as potential therapeutic strategies due to their diverse mechanisms of antiviral activity. MPXV produces two key infectious particles: the mature virion (MV) and the extracellular enveloped virion (EV), both essential for infection and spread. Effective therapies must target both to halt replication and transmission. Our prior research demonstrated the development of a potent neutralizing mAb against MPXV MV. This study focuses on developing a plant-derived mAb targeting MPXV EV, which is critical for viral dissemination within the host and generally resistant to antibody neutralization. Our findings reveal that the mAb (H2) can be robustly produced in Nicotiana benthamiana plants via transient expression. The plant-made H2 mAb effectively targets MPXV EV by binding specifically to the A35 MPXV antigen. Importantly, H2 mAb shows notable neutralizing activity against the infectious MPXV EV particle. This investigation is the first to report the development of a plant-derived anti-EV mAb for MPXV prevention and treatment, as well as the first demonstration of anti-MPXV EV activity by an mAb across any production platform. It highlights the potential of plant-produced mAbs as therapeutics for emerging infectious diseases, including the MPXV outbreak.

2022年，猴痘病毒（MPXV）在全球范围内的爆发，以及人传人传播能力的增强，促使公共卫生干预措施迅速展开。鉴于植物来源的单克隆抗体（mAbs）具有多种抗病毒活性的机制，它们被探索作为潜在的治疗策略。MPXV产生两种关键感染性颗粒：成熟的病毒颗粒（MV）和细胞外包膜病毒颗粒（EV），两者均为感染和传播所必需。有效的治疗方法必须针对两者以阻止复制和传播。我们先前的研究展示了针对MPXV MV的强效中和mAb的研发。本研究聚焦于开发一种靶向MPXV EV的植物来源的mAb，后者对于病毒在宿主体内的传播至关重要，并且通常对抗体中和具有抵抗力。我们的研究结果表明，该mAb（H2）可以通过瞬时表达在烟草花叶（Nicotiana benthamiana）植物中稳定生产。植物生产的H2 mAb能够通过特异性结合A35 MPXV抗原有效地靶向MPXV EV。重要的是，H2 mAb对感染性MPXV EV颗粒表现出显著的中和活性。本研究首次报告了植物来源的针对EV的mAb在MPXV的预防和治疗中的应用，以及首次证明了任何生产平台上的mAb对MPXV EV的抗活性。这突出了植物生产的mAbs作为新兴传染病（包括MPXV爆发）治疗药物的潜力。