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TitleDiscovery and Structural Characterization of a Highly Protective Neutralizing Antibody Targeting the Mpox Virus A35R Protein.
Journal, issue, pagesMedComm (2020), Vol. 7, Page e70804, Year 2026
Publish dateMay 18, 2026
AuthorsShimeng Bai / Shuo Song / Xin Wang / Yuxin Xiao / Yun Long / Fenfang Wu / Fuxiang Wang / Zhongyi Fan / Jianqing Xu / Maozhou He / Hongzhou Lu /
PubMed AbstractThe recent resurgence of the mpox virus (MPXV) has raised global health concerns due to its potential to cause severe illness in vulnerable populations. Targeting the extracellular enveloped virus ...The recent resurgence of the mpox virus (MPXV) has raised global health concerns due to its potential to cause severe illness in vulnerable populations. Targeting the extracellular enveloped virus (EEV) protein A35R is a promising strategy to restrict viral dissemination within the host. In this study, we combined mRNA-LNP immunization with the Beacon Optofluidic system to rapidly screen and isolate high-affinity monoclonal antibodies. One of these antibodies, 17H1, exhibited exceptional neutralization against authentic MPXV. Cryo-electron microscopy (Cryo-EM) analysis revealed that 17H1 binds to a specific epitope at the distal ends of the A35R dimer. The interaction is stabilized by a unique network of hydrogen bonds and salt bridges, particularly involving residue E120, distinguishing its binding mode from previously reported A35R antibodies. Furthermore, 17H1 exhibited complete protective efficacy against MPXV infection in vivo and significantly reduced pulmonary viral load and lung pathogenesis. These findings highlight 17H1 as a promising therapeutic candidate for novel mpox interventions.
External linksMedComm (2020) / PubMed:42358411 / PubMed Central
MethodsEM (single particle)
Resolution3.63 Å
Structure data

80928
EMDB Unreleased entry

26wc

EMDB-80928, PDB-26wc:
Local refinement of the mpox virus A35R protein in complexed with 17H1 Fab
Method: EM (single particle) / Resolution: 3.63 Å

Source
  • monkeypox virus
  • mus musculus (house mouse)
KeywordsVIRAL PROTEIN / Immune Complex

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