PoxviRus cOnTrolled EmergenCy using Therapeutics and Innovative VaccinEs

Recent Monkeypox (mpox) outbreaks have caught once again the world unprepared. Low-middle income countries are currently most affected by mpox, however cases keep being reported worldwide. The continues circulation of mpox can rapidly burst in a global crisis that can set-back our world into chaos, reminiscing the recent pandemic. Lack of effective and affordable medical interventions urges the need to develop innovative countermeasures against orthopoxviruses. Recent technologies and methodological advancements allow to develop vaccines and monoclonal antibodies (mAbs) in record time, and their use can be vital to stop current and future orthopoxvirus-related threats. Here we propose to discover and develop mAbs against mpox and other orthopoxviruses. These reagents will be crucial to identify and design novel protective antigens to develop innovative vaccines. We will isolate, through an antigen-agnostic approach, mAbs from mpox infected or vaccinated individuals to build a panel of neutralizing mAbs (nAbs) able to recognize orthopoxviruses shared and protective epitopes. Generative artificial intelligence will be systemically integrated in our workflow to identify antigens targeted by discovered nAbs at unprecedented speed. Data-augmentation and iterative deep-learning models will be used to in silico design new vaccine immunogens which can be produced as recombinant proteins or mRNA, or loaded on nanoparticles. This approach will provide broadly nAbs and effective vaccines designed to protect from mpox and other orthopoxviruses. If successful, the approach herein proposed will fuel the field of vaccinology allowing unprecedent speed for antigen discovery and vaccine development. This approach could be translated to all pathogens for which no cure or prevention are available including emerging viral pathogens and antimicrobial resistant bacteria. This will strongly increase European competitiveness in fighting infectious disease and control future crisis.