ENHANCED MANUFACTURING OF BROADLY POTENT EQUINE POLYCLONAL FAB WITH A RATIONAL IMMUNIZATION STRATEGY AGAINST CORONAVIRUSES

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 antibodiesin 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.