Isolation and Characterization of E8 Monoclonal Antibodies from Donors Vaccinated with Recombinant Vaccinia Vaccine with Efficient Neutralization of Authentic Monkeypox Virus

作者：Yutao Shi, Shuhui Wang, Yanling Hao, Xiuli Shen, Jun Zhang, Shuo Wang, Junjie Zhang, Yuyu Fu, Ran Chen, Dong Wang, Yiming Shao, Dan Li, Ying Liu · 发表于：Vaccines · 年份：2025 · DOI：10.3390/vaccines13050471 · 被引用次数：8 · 研究领域：Poxvirus research and outbreaks、Immunotherapy and Immune Responses、vaccines and immunoinformatics approaches

Background/Objectives: Monkeypox, twice declared a public health emergency of international concern by the WHO, currently lacks approved targeted therapeutics. This study focused on the development of monkeypox virus (MPXV) E8-specific human monoclonal antibodies (mAbs) derived from recipients of the recombinant vaccinia vaccine (rTV), with subsequent evaluation of their cross-neutralizing activity against orthopoxviruses, including the vaccinia virus (VACV) and MPXV. Methods: Three mAbs (C5, C9, and F8) were isolated from rTV vaccinees. Structural mapping characterized their binding domains on the MPXV E8 and VACV D8 proteins. Neutralization potency was assessed against the VACV TianTan strain and MPXV clade IIb. A combo was further evaluated in a VACV-infected mice model for clinical recovery and viral load reduction. Complement-dependent enhancement mechanisms were also investigated in vitro. Results: C9 targets the virion surface region of E8 and both the virion surface region and intravirion region of D8, showing cross-neutralization activity against the MPXV (IC50 = 3.0 μg/mL) and VACV (IC50 = 51.1 ng/mL) in vitro. All three antibodies demonstrated potent neutralization against the VACV in vitro: C5 (IC50 = 3.9 ng/mL), C9 (IC50 = 51.1 ng/mL), and F8 (IC50 = 101.1 ng/mL). Notably, complement enhanced neutralization against the VACV by >50-fold, although no enhancement was observed for the MPXV. In vivo administration accelerated clinical recovery by 24 h and achieved ...