2025-12-10 テキサス大学オースチン校 (UT Austin)
<関連情報>
- https://news.utexas.edu/2025/12/10/ai-tips-off-scientists-to-new-drug-target-to-fight-treat-monkeypox-virus/
- https://www.science.org/doi/10.1126/scitranslmed.aeb3840
OPG153を標的とするポックスウイルス広域中和抗体の抗原非依存同定 Antigen-agnostic identification of poxvirus broadly neutralizing antibodies targeting OPG153
Ida Paciello, Emily J. Rundlet, Ling Zhou, Giulia Realini, […] , and Emanuele Andreano
Nature Translational Medicine Published:10 Dec 2025
DOI:https://doi.org/10.1126/scitranslmed.aeb3840
Editor’s summary
Two recent outbreaks of mpox, caused by monkeypox virus (MPXV), underscore the urgent need to develop and stockpile effective vaccines and therapeutics. Here, Paciello et al. applied Reverse Vaccinology 2.0 combined with AI to identify an MPXV protein targeted by human B cells to enable the development of antibody therapeutics and vaccines. The authors recombinantly expressed MPXV-neutralizing antibodies derived from B cells of individuals who had a history of MPXV infection or vaccination. They next used AI-assisted modeling and cryo-EM to identify the target of a subset of potent, broadly neutralizing antibodies as the protein encoded by the conserved orthopoxviral gene (OPG) 153. Immunization of mice with an adjuvanted MPXV OPG153 vaccine elicited neutralizing antibodies, suggesting that OPG153 represents both a candidate vaccine antigen and a therapeutic antibody target. Together, these findings highlight the power of leveraging human immunity to design therapeutics and vaccines. —Courtney Malo
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.
