8XS3

Structure of MPXV B6 and D68 fab complex

Summary for 8XS3

• Entry DOI: 10.2210/pdb8xs3/pdb
• EMDB information: 38613
• Descriptor: D68_heavy chain, D68_light chain, Protein OPG190, ... (5 entities in total)
• Functional Keywords: mpxv antibody, viral protein/immune system, viral protein-immune system complex
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 3
• Total formula weight: 77556.25

Authors

wu, L.L.,Sun, J.Q. (deposition date: 2024-01-08, release date: 2024-06-12, Last modification date: 2025-07-23)

Primary citation

Zhao, R.,Wu, L.,Sun, J.,Liu, D.,Han, P.,Gao, Y.,Zhang, Y.,Xu, Y.,Qu, X.,Wang, H.,Chai, Y.,Chen, Z.,Gao, G.F.,Wang, Q.
Two noncompeting human neutralizing antibodies targeting MPXV B6 show protective effects against orthopoxvirus infections.
Nat Commun, 15:4660-4660, 2024

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.

PubMed: 38821921
DOI: 10.1038/s41467-024-48312-2

Experimental method

ELECTRON MICROSCOPY (3.46 Å)