Innovative Monoclonal antibody against Poxviruses for Advanced CounTermeasures

To strengthen Europe's biodefence preparedness and responsiveness to epidemic and deliberate threats, the IMPACT project will develop the first antibody-based countermeasure for orthopoxviruses, targeting both variola major virus (VARV) and monkeypox virus (MPXV) with a single antibody. The project brings together a consortium of leading European institutions, many belonging to the European Vaccine Hub (EVH) network, with proven expertise in monoclonal antibody (mAb) discovery, structural biology, computational modelling, immunology, virology, pre-clinical models, GMP manufacturing, regulatory science, and clinical trial execution. The broadly neutralizing mAbs proposed target OPG153 (MPXV A28), a recently discovered conserved antigen, representing a breakthrough in orthopoxvirus countermeasures. These mAbs combine nanogram-per-millilitre potency, dual neutralisation of mature and extracellular virions, and cross-neutralisation across MPXV clades and vaccinia virus, with cross-reactivity to cowpox and VARV orthologues in a single molecule. We will use AI-driven optimization of mAbs to enhance functional activities and protein engineering to extend half-life. Selected candidates will then be tested in pre-clinical murine and non-human primate models to evaluate prophylactic and therapeutic efficacy against different orthopoxviruses. The most promising candidate will subsequently be manufactured under GMP conditions and assessed in a phase I clinical trial. In parallel, analyses of more than 1,800 sera from infected and vaccinated individuals will be performed to characterise the response to OPG153 and possibly identify correlates of protection, providing a critical foundation for regulatory approval. By combining world-class science with European strategic infrastructures, IMPACT will deliver not only a deployable first-in-class therapeutic but also a decisive biodefence tool, reinforcing Europe's leadership and resilience against epidemic and biothreat pathogens.