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广泛中和的人类单克隆抗体对抗BK多重瘤病毒基因型

J Andrew Duty^1,2, Thomas A Kraus², Madhu Kumar¹

¹Center for Therapeutic Antibody Development, Drug Discovery Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10709, USA.

The Journal of general virology

|December 22, 2025

概括

研究人员开发了广泛中和的人类单克隆抗体 (mAbs),针对BK多重瘤病毒 (BKV) I-IV基因型. 这些新型抗体显示出对移植受体BKV感染的治疗潜力.

科学领域:

免疫学和病毒学

背景情况:

在移植受体中,BK多重瘤病毒 (BKV) 会导致严重的并发症,如脏病和出血性囊炎.
目前的治疗方法包括降低免疫抑制,但BKV菌株表现出遗传多样性 (I-IV基因型),使管理复杂化.
BKV 中和抗体在限制病毒载量方面表现有前途,表明潜在的治疗标.

研究的目的:

产生广泛中和的人类单克隆抗体 (mAbs) 对抗BK多瘤病毒 (BKV) VP1主要囊蛋白跨基因型I-IV.
识别和描述具有BKV感染治疗潜力的新型mAbs.

主要方法:

使用VelocImmune®转基因小鼠免疫BKV基因型I-IV VP1蛋白和伪病毒 (BK-PsVs).
使用高通量结合试验选混合瘤克隆,并对各种BKV基因型评估中和活性.
测序和表征有前途的交叉中和mAbs,包括与IgG1 Fc域的人性化.

主要成果:

确定了36种广泛交叉中和的mAbs,对BKV基因型I-IV有效.
描述了14种不同的免疫球蛋白,分为6个克隆型家族.
开发出完全人性化的IgG1mAbs,证明了低皮科莫尔IC50值的所有四种BKV基因型的强有力的中和.

结论:

产生了高度有效的,广泛中和的人类mAbs,准BKV VP1蛋白.
这些交叉中和的mAbs代表了开发新型BKV疗法的有希望的生物候选者.
这些发现提供了一种潜在的新策略,用于在免疫受损患者中管理与BKV相关的疾病.

关键词:

BK多种病毒 (BKV)人类干细胞移植 (HST)单克隆抗体 (mAbs) 是一种单克隆抗体.与多种病毒相关的出血性囊炎 (PyVHC)聚瘤病毒相关性病 (PyVAN)

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