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TitleAntigen-agnostic identification of poxvirus broadly neutralizing antibodies targeting OPG153.
Journal, issue, pagesSci Transl Med, Vol. 17, Issue 828, Page eaeb3840, Year 2025
Publish dateDec 10, 2025
AuthorsIda Paciello / Emily J Rundlet / Ling Zhou / Giulia Realini / Federica Perrone / Giulio Pierleoni / Marco Troisi / Jeanne Postal / Florence Guivel-Benhassine / Françoise Porrot / Connor M Mullins / Davide Moschese / Maria Vittoria Cossu / Federico Sabaini / Silvia Accordini / Natasha Gianesini / Rebeca Passarelli Mantovani / Francesca Panza / Massimiliano Fabbiani / Mario Tumbarello / Spinello Antinori / Concetta Castilletti / Francesca Montagnani / Olivier Schwartz / Rino Rappuoli / Jason S McLellan / Emanuele Andreano /
PubMed AbstractRecurrent mpox outbreaks caused by the monkeypox virus (MPXV) have prompted the World Health Organization to declare a Public Health Emergency of International Concern and have stimulated the ...Recurrent mpox outbreaks caused by the monkeypox virus (MPXV) have prompted the World Health Organization to declare a Public Health Emergency of International Concern and have stimulated the development of medical interventions. Here, we used antigen-agnostic identification of MPXV-neutralizing monoclonal antibodies from convalescent or vaccinated people, AlphaFold 3-based predictive modeling, and cryo-electron microscopy to identify the protein encoded by orthopoxviral gene (OPG) 153 (MPXV A28) as a target of broadly neutralizing antibodies. OPG153-targeting antibodies neutralized MPXV clades Ib and IIb and vaccinia virus (VACV) and cross-reacted with OPG153 orthologs from cowpox and variola viruses. Immunization with MPXV OPG153 elicited a potent neutralizing antibody response against MPXV and VACV in mice, substantiating OPG153 as both a promising vaccine antigen and a potent target for preventive and therapeutic antibodies.
External linksSci Transl Med / PubMed:41370398
MethodsEM (single particle)
Resolution2.8 - 3.2 Å
Structure data

70449

9og1

EMDB-70449, PDB-9og1:
Globular domain of monkeypox virus OPG153 (A28) bound to antibody 02M12
Method: EM (single particle) / Resolution: 3.2 Å

70450

9og2

EMDB-70450, PDB-9og2:
Globular domain of monkeypox virus OPG153 (A28) in complex with antibodies 08E11 and 12I12
Method: EM (single particle) / Resolution: 2.8 Å

Source
  • homo sapiens (human)
  • monkeypox virus
KeywordsVIRAL PROTEIN / Monkeypox virus / neutralizing antibody / orthopoxvirus / neutralizing antibodies

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