Mesh : Animals Mice, Inbred BALB C Humans Female Antibodies, Neutralizing / immunology Antibodies, Viral / immunology Mice Antibodies, Monoclonal / immunology Epitopes / immunology Monkeypox virus / immunology Poxviridae Infections / immunology prevention & control Vaccinia virus / immunology Orthopoxvirus / immunology Mpox (monkeypox) / immunology prevention & control

来  源:   DOI:10.1038/s41467-024-48312-2   PDF(Pubmed)

Abstract:
The recent outbreak of mpox epidemic, caused by monkeypox virus (MPXV), poses a new threat to global public health. Here, we initially assessed the preexisting antibody level to the MPXV B6 protein in vaccinia vaccinees born before the end of the immunization program and then identified two monoclonal antibodies (MAbs), hMB621 and hMB668, targeting distinct epitopes on B6, from one vaccinee. Binding assays demonstrate that both MAbs exhibit broad binding abilities to B6 and its orthologs in vaccinia (VACV), variola (VARV) and cowpox viruses (CPXV). Neutralizing assays reveal that the two MAbs showed potent neutralization against VACV. Animal experiments using a BALB/c female mouse model indicate that the two MAbs showed effective protection against VACV via intraperitoneal injection. Additionally, we determined the complex structure of B6 and hMB668, revealing the structural feature of B6 and the epitope of hMB668. Collectively, our study provides two promising antibody candidates for the treatment of orthopoxvirus infections, including mpox.
摘要:
最近爆发的水痘疫情,由猴痘病毒(MPXV)引起,对全球公共卫生构成了新的威胁。这里,我们最初评估了免疫计划结束前出生的牛痘疫苗中MPXVB6蛋白的预先存在的抗体水平,然后鉴定了两种单克隆抗体(MAb),hMB621和hMB668,靶向B6上的不同表位,来自一名疫苗。结合测定表明,两种单克隆抗体在牛痘(VACV)中对B6及其直系同源物表现出广泛的结合能力,天花(VARV)和牛痘病毒(CPXV)。中和测定显示,两种MAb显示针对VACV的有效中和。使用BALB/c雌性小鼠模型的动物实验表明,两种MAb通过腹膜内注射显示出针对VACV的有效保护。此外,我们确定了B6和hMB668的复合结构,揭示了B6的结构特征和hMB668的表位。总的来说,我们的研究提供了两种有希望的候选抗体,用于治疗正痘病毒感染,包括水痘.
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