2025/08/18 by Ida Paciello, Ling Zhou, Emily J. Rundlet +24 · 1 voice
Immunology and Microbiology · Biochemistry, Genetics and Molecular Biology · Medicine · #Poxvirus research and outbreaks #Virus-based gene therapy research #Herpesvirus Infections and Treatments
paper · pdf · doi:10.1101/2025.08.15.670377
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, antigen-agnostic isolation of neutralizing monoclonal antibodies from convalescent or vaccinated people, AlphaFold 3-based predictive modeling, and cryo-electron microscopy were synergistically combined to identify the protein encoded by orthopoxviral gene (OPG) 153 (MPXV A28) as a target of broadly neutralizing antibodies. OPG153-targeting antibodies neutralized MPXV clade Ib, 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, substantiating OPG153 as a promising vaccine antigen and a potent target for preventive and therapeutic antibodies.