Structural highlights
FunctionPublication Abstract from PubMedRecurrent 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. Antigen-agnostic identification of poxvirus broadly neutralizing antibodies targeting OPG153.,Paciello I, Rundlet EJ, Zhou L, Realini G, Perrone F, Pierleoni G, Troisi M, Postal J, Guivel-Benhassine F, Porrot F, Mullins CM, Moschese D, Cossu MV, 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 JS, Andreano E Sci Transl Med. 2025 Dec 10;17(828):eaeb3840. doi: 10.1126/scitranslmed.aeb3840. , Epub 2025 Dec 10. PMID:41370398[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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