美国西奈山伊坎医学院Camila H. Coelho团队揭示了靶向A35的人源单克隆抗体可防止猴痘引起的死亡。相关论文于2025年8月26日发表于国际顶尖学术期刊《细胞》杂志上。
从一名mpox恢复期个体中，该课题组人员鉴定出三种高亲和力的人单克隆抗体（mAbs）（命名为EV35-2、EV35-6和EV35-7），它们靶向MPXV中的A35蛋白。这些抗体阻断病毒在体外的传播，并通过Fc依赖性和独立机制保护小鼠免受致命的MPXV和牛痘病毒感染。针对相同表位的血清抗体水平在mpox恢复期的人中升高，血清中这些抗体水平升高与症状持续时间缩短和不住院有关。
系统水平的多变量分析表明，针对相同表位区域的mpox-恢复期血清抗体与这三种单克隆抗体可能协同起作用，与临床保护具有附加关联。其中两种抗体在其CDRH3区域定位保守的IGHD2-21编码的CxGGDCx基序，结合高度保守的痘病毒表位。这些发现确立了A35作为一个关键的治疗靶点，并突出了A35特异性单克隆抗体作为下一代正痘病毒治疗的有希望的候选者。
研究人员表示，2022年猴痘疫情凸显了猴痘病毒（MPXV）的严重威胁，但缺乏有效的治疗方法。
附：英文原文
Title: Human monoclonal antibodies targeting A35 protect from death caused by mpox
Author: Raianna F. Fantin, Meng Yuan, Seok-Chan Park, Bailey Bozarth, Hallie Cohn, Maxinne Ignacio, Patricia Earl, Alesandro Civljak, Gabriel Laghlali, Ding Zhang, Xueyong Zhu, Jameson Crandell, Valter Monteiro, Jordan J. Clark, Catherine Cotter, Martin Burkhardt, Gagandeep Singh, Prajakta Warang, Juan García-Bernalt Diego, Komal Srivastava, Luz A. Lugo, Lauren Pischel, Inci Yildirim, Saad B. Omer, Daniel da Silva, Florian Krammer, Goran Bajic, Viviana Simon, Michael Schotsaert, Carolina Lucas, Ian A. Wilson, Bernard Moss, Camila H. Coelho
Issue&Volume: 2025-08-26
Abstract: The 2022 mpox outbreak highlighted the serious threat of monkeypox virus (MPXV), yet effective treatments are lacking. From an mpox-convalescent individual, we identified three high-affinity human monoclonal antibodies (mAbs) (named EV35-2, EV35-6, and EV35-7) that target the A35 protein in MPXV. These antibodies block viral spread in vitro and protect mice against lethal MPXV and vaccinia virus infection via both Fc-dependent and independent mechanisms. Levels of serum antibodies targeting the same epitopes are increased in mpox-convalescent humans, and higher levels of these antibodies in the sera are linked to shorter symptom duration and no hospitalization. Systems-level multivariate analysis indicated that mpox-convalescent serum antibodies targeting the same epitopic region as these three mAbs may function cooperatively, with additive associations to clinical protection. Two of the antibodies use a conserved IGHD2-21-encoded CxGGDCx motif in their CDRH3 region to bind a highly conserved poxvirus epitope. These findings establish A35 as a critical therapeutic target and highlight A35-specific mAbs as promising candidates for next-generation orthopoxvirus treatments.
DOI: 10.1016/j.cell.2025.08.004
Source: https://www.cell.com/cell/abstract/S0092-8674(25)00918-3