Bispecific antibodies targeting MPXV A29 and B6 demonstrate efficacy against MPXV infection

作者：Mengjun Li, Jiayin Chen, Fungxiang Wang, Jiahua Kuang, Yun Peng, Sadia Asghar, Wei Zhao, Yang Yang, Chenguang Shen · 发表于：Journal of Virology · 年份：2025 · DOI：10.1128/jvi.02320-24 · 被引用次数：7 · 研究领域：Poxvirus research and outbreaks、Herpesvirus Infections and Treatments、Bacillus and Francisella bacterial research

ABSTRACT Recently, the monkeypox virus (MPXV) outbreak was once again declared by the World Health Organization as a global health emergency, and currently, there is no specific drug against MPXV. During the replication cycle, MPXV produces two distinct forms of viral particles: extracellular enveloped virus (EEV), released via exocytosis, and intracellular mature virus (IMV), expelled through host cell lysis. A29 and B6 proteins are membrane proteins found on the IMV and EEV viral particles, respectively. This study designed two different bispecific antibodies (bsAbs) targeting specific antigens of the MPXV: the developed bsAb 9F8-3A1 targets two non-competitive binding epitopes on the MPXV protein A29, while bsAb 9F8-7C9 targets different antigen-binding epitopes on both A29 and B6. The in vitro and in vivo characterization assays demonstrated that the bsAbs provided complete protection against three poxvirus strains: vaccinia virus (VACV) Tiantan, VACV Western Reserve (VACV WR), and MPXV, surpassing the efficacy of all the parental monoclonal antibodies. Notably, the bsAb 9F8-7C9 exhibited the most effective antiviral activity. In vivo pharmacokinetic experiments showed that these two bsAbs have long half-lives in rhesus macaques. In conclusion, this study successfully developed two bispecific antibodies that target different epitopes, providing crucial insights for the development of decent antiviral drugs against MPXV and other orthopoxviruses. IMPORTANCE Mpox is a viral...