PDF(Pubmed)
Abstract：
The eradication of smallpox was officially declared by the WHO in 1980, leading to discontinuation of the vaccination campaign against the virus. Consequently, immunity against smallpox and related orthopoxviruses like Monkeypox virus gradually declines, highlighting the need for efficient countermeasures not only for the prevention, but also for the treatment of already exposed individuals. We have recently developed human-like monoclonal antibodies (mAbs) from vaccinia virus-immunized non-human primates. Two mAbs, MV33 and EV42, targeting the two infectious forms of the virus, were selected for in vivo evaluation, based on their in vitro neutralization potency. A single dose of either MV33 or EV42 administered three days post-infection (dpi) to BALB/c female mice provides full protection against lethal ectromelia virus challenge. Importantly, a combination of both mAbs confers full protection even when provided five dpi. Whole-body bioimaging and viral load analysis reveal that combination of the two mAbs allows for faster and more efficient clearance of the virus from target organs compared to either MV33 or EV42 separately. The combined mAbs treatment further confers post-exposure protection against the currently circulating Monkeypox virus in Cast/EiJ female mice, highlighting their therapeutic potential against other orthopoxviruses.
摘要：
世界卫生组织于1980年正式宣布根除天花，导致停止了针对该病毒的疫苗接种运动。因此,对天花和相关正痘病毒如猴痘病毒的免疫力逐渐下降，强调需要有效的对策，不仅是为了预防，也用于治疗已经暴露的个体。我们最近从牛痘病毒免疫的非人灵长类动物中开发了类似人的单克隆抗体（mAb）。两个单克隆抗体，MV33和EV42，针对两种感染形式的病毒，被选择用于体内评估，基于它们的体外中和效力。在感染后3天(dpi)给予BALB/c雌性小鼠的MV33或EV42的单剂量提供了针对致死性外胚层病毒攻击的完全保护。重要的是,即使提供五个dpi，两种mAb的组合也可提供全面保护。全身生物成像和病毒载量分析显示，与MV33或EV42分开相比，两种mAb的组合可以更快，更有效地从靶器官清除病毒。联合的单克隆抗体治疗进一步赋予Cast/EiJ雌性小鼠对当前流行的猴痘病毒的暴露后保护，强调它们对其他正痘病毒的治疗潜力。
