结合的人类广泛中和抗体对乙型肝炎病毒的体内疗效
Maxime Beretta1, Ariel Mechaly2, Cyril Planchais1
1Institut Pasteur, Université Paris Cité, Humoral Immunology Unit, 75015 Paris, France.
Cell reports
|December 17, 2025
概括
针对乙型肝炎病毒 (HBV) preS2和小 (S) 抗原的新人类单克隆抗体显示出强大的抗病毒活性. 结合这些抗体可显著降低小鼠中的HBV感染标志物,为疫苗和免疫疗法提供了希望.
科学领域:
- 免疫学 免疫学 免疫学
- 病毒学 病毒学
- 疫苗开发 疫苗开发
背景情况:
- 对乙型肝炎病毒 (HBV) 表面抗原 (HBsAg) 的抗体对于控制HBV感染至关重要.
- 这些抗体的精确分子和功能特征尚未完全理解.
- 了解HBsAg的抗体标是开发有效的HBV疗法和疫苗的关键.
研究的目的:
- 针对preS1,preS2和HBsAg.小 (S) 区域的人类B细胞单克隆抗体的记忆特征.
- 评估这些抗体的中和能力和体内抗病毒疗效,特别是抗preS2抗体.
- 探索将不同类型的广泛中和抗体 (bNAbs) 结合在一起,以提高HBV控制的潜力.
主要方法:
- 从HBV血清转化剂中分离和表征单克隆抗体.
- 对抗体活性,HBV的中和和Fc依赖的效应因子功能的评估.
- 在HBV载体小鼠体内使用联合抗体治疗的实体疗效研究.
- 抗体-抗原相互作用的表皮图谱绘制和结构分析.
主要成果:
- 广泛反应的抗preS2抗体被发现可以中和HBV,并在体内表现出显著的Fc依赖性抗病毒活性.
- 这些抗preS2抗体向preS2区域N端的免疫主导表位.
- 同一个捐赠者的抗preS2和抗S bNAbs的联合治疗导致HBV携带小鼠的抗原血和病毒血的深刻而持久的减少.
结论:
- 抗preS2抗体对HBV具有显著的抗病毒潜力.
- 将抗preS2抗体与强大的抗S bNAbs结合起来,为持久的HBV抑制提供了一个有希望的策略.
- 这些发现支持开发增强型HBV疫苗和新型免疫疗法.
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