Descrizione del progetto
Innovazioni nell’iperimmunizzazione per combattere le minacce virali
Di fronte alla minaccia di epidemie virali, le terapie convenzionali sono insufficienti a causa della limitata efficacia contro agenti patogeni in rapida evoluzione. Le attuali strategie di immunizzazione si scontrano con il panorama in continua evoluzione delle sottofamiglie virali, lasciando una lacuna critica nelle nostre difese. In questo contesto, il progetto e-FabRIC, finanziato dall’UE, svilupperà una strategia di iperimmunizzazione mirata alla sottofamiglia dei sarbecovirus. Genererà immunoglobuline equine con un’ampiezza di neutralizzazione senza precedenti. Utilizzando frammenti F(ab’)2 purificati, un prodotto farmaceutico di provata efficacia, il progetto utilizza un antigene a mosaico per stimolare risposte anticorpali diverse nei singoli cavalli. Mettendo insieme queste specificità, l’approccio innovativo di e-FabRIC dà vita a una potente immunoterapia con un’ampia attività di neutralizzazione virale. Questa scoperta permette di affrontare minacce come la COVID-19 e di gettare le basi per combattere le future epidemie virali.
Obiettivo
e-FabRIC will develop a new hyperimmunization strategy for generating high titers equine immunoglobulins having a broad neutralizing specificity against viral targets belonging to same subfamily phylogenic tree. The viral subfamily selected to demonstrate the unique benefits of this innovative way to induce highly anti-viral active antibodies is the sarbecovirus subfamily. The equine antibodies will be processed as purified F(ab’)2 fragments, a well-known pharmaceutical product with a strong historical safety record in human patients. The F(ab’)2 antibody fragments generated by e-FabRIC are expected to display a unique and very wide neutralizing activity spectrum. This new property will be the synergistic outcome of the immunization with a nanoparticle co-displaying 8 different sarbecovirus RBD subunits (designated as “mosaic antigen”) and the natural immunogenetic diversity present in individual horses. In each individual horse, the mosaic antigen immunization will drive the generation and maturation of antibodies highly focused on conserved epitope structures shared by the different sarbecovirus RBD subunits and associated with viral neutralization. As each horse's own immunogenetics will mature the mosaic antigen-specific antibodies in a different way, several equine individual antibody specificities will be pooled in order to expand the overall broad viral neutralizing activity of the final pharmaceutical product. The combined multiplicity of individual antibody response diversities and the highly focused antibody responses induced by the mosaic antigen will be the basis of a broadly potent, immunotherapy pharmaceutical F(ab’)2-based product able to significantly reduce the clinical and societal impact of any emergence of a new human sarbecovirus outbreak. The scientific and technical learnings of this new and powerful immunization strategy will be applicable to other viral families from which human infectious threats may arise.
Campo scientifico
- medical and health sciencesbasic medicineimmunologyimmunisation
- medical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugs
- medical and health scienceshealth sciencesinfectious diseasesRNA virusescoronaviruses
- engineering and technologynanotechnologynano-materials
- medical and health sciencesbasic medicineimmunologyimmunotherapy
Parole chiave
Programma(i)
Meccanismo di finanziamento
HORIZON-RIA - HORIZON Research and Innovation ActionsCoordinatore
69007 Lyon
Francia
L’organizzazione si è definita una PMI (piccola e media impresa) al momento della firma dell’accordo di sovvenzione.