9OG1

Globular domain of monkeypox virus OPG153 (A28) bound to antibody 02M12

Summary for 9OG1

• Entry DOI: 10.2210/pdb9og1/pdb
• EMDB information: 70449
• Descriptor: A28L, Monoclonal antibody 02M12 heavy chain, Monoclonal antibody 02M12 light chain (3 entities in total)
• Functional Keywords: monkeypox virus, neutralizing antibody, orthopoxvirus, viral protein
• Biological source: Monkeypox virus; More
• Total number of polymer chains: 3
• Total formula weight: 74037.36

Authors

Rundlet, E.J.,Zhou, L.,McLellan, J.S. (deposition date: 2025-04-30, release date: 2025-12-24)

Primary citation

Paciello, I.,Rundlet, E.J.,Zhou, L.,Realini, G.,Perrone, F.,Pierleoni, G.,Troisi, M.,Postal, J.,Guivel-Benhassine, F.,Porrot, F.,Mullins, C.M.,Moschese, D.,Cossu, M.V.,Sabaini, F.,Accordini, S.,Gianesini, N.,Passarelli Mantovani, R.,Panza, F.,Fabbiani, M.,Tumbarello, M.,Antinori, S.,Castilletti, C.,Montagnani, F.,Schwartz, O.,Rappuoli, R.,McLellan, J.S.,Andreano, E.
Antigen-agnostic identification of poxvirus broadly neutralizing antibodies targeting OPG153.
Sci Transl Med, 17:eaeb3840-eaeb3840, 2025

PubMed Abstract: 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.

PubMed: 41370398
DOI: 10.1126/scitranslmed.aeb3840

Experimental method

ELECTRON MICROSCOPY (3.2 Å)