State Key Laboratory of Organ Failure Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, People's Republic of China.
BSL-3 Laboratory (Guangdong), Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health; Department of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, People's Republic of China.
Emerg Microbes Infect. 2024 Dec;13(1):2401931. doi: 10.1080/22221751.2024.2401931. Epub 2024 Sep 19.
In 2022, the monkeypox virus (mpox virus, MPXV) exhibited global dissemination across six continents, representing a notable challenge owing to the scarcity of targeted antiviral interventions. Passive immunotherapy, such as the use of monoclonal antibodies (mAbs) and bispecific antibodies (bsAbs), has emerged as a promising option for antiviral regimens. Here, we generated several mAbs against M1R and B6R of MPXV, and subsequently characterized the antiviral activity of these antibodies both and . Two neutralizing mAbs, M1H11 and M3B2, targeting M1R, and one B6R-specific mAb, B7C9, were identified. They exhibited varying antiviral efficacy against vaccinia virus (VACV) and . A cocktail comprising M1H11 and M3B2 demonstrated a superior protective effect . A bsAb, Bis-M1M3, was engineered by conjugating the fragment crystallizable (Fc) region of the human-mouse chimeric engineered M1H11 with the single-chain fragment variable (scFv) of M3B2. In mice challenged with MPXV, Bis-M1M3 showed a notable protective effects. Analysis of neutralization mechanism showed that these mAbs and Bis-M1M3 exerted virus-neutralizing effects before the virus infects cells. pharmacokinetic experiments showed that Bis-M1M3 has a long half-life in rhesus macaques. This study provides crucial insights for further research on broad-spectrum antiviral drugs against MPXV and other orthopoxviruses.
2022 年，猴痘病毒（mpox 病毒，MPXV）在六大洲广泛传播，由于缺乏靶向抗病毒干预措施，这是一个显著的挑战。被动免疫疗法，如使用单克隆抗体（mAbs）和双特异性抗体（bsAbs），已成为抗病毒方案的一个有前途的选择。在这里，我们针对 MPXV 的 M1R 和 B6R 生成了几种 mAbs，并随后对这些抗体的抗病毒活性进行了 和 的表征。鉴定了两种针对 M1R 的中和 mAb，M1H11 和 M3B2，以及一种针对 B6R 的 mAb B7C9。它们对痘苗病毒（VACV）和 的抗病毒效果不同。包含 M1H11 和 M3B2 的鸡尾酒显示出更好的保护效果。双特异性抗体 Bis-M1M3 通过将人-鼠嵌合工程化 M1H11 的 Fc 区与 M3B2 的单链片段可变区（scFv）缀合而构建。在感染 MPXV 的小鼠中，Bis-M1M3 显示出显著的保护作用。中和机制分析表明，这些 mAbs 和 Bis-M1M3 在病毒感染细胞之前发挥了病毒中和作用。药代动力学实验表明，Bis-M1M3 在恒河猴体内具有较长的半衰期。这项研究为进一步研究针对 MPXV 和其他正痘病毒的广谱抗病毒药物提供了重要的见解。
