The long-term objective of this work is to develop a monoclonal antibody product for the prevention and treatment of EV-D68 respiratory disease and acute flaccid myelitis (AFM). EV- 68 is an emerging picornavirus that has caused outbreaks of respiratory disease and is associated with AFM, which is a polio-like illness. The peak incidence of EV-D68 infections is August to October every other year since emerging in 2014. AFM exclusively affects children, while the respiratory manifestations affect both adults and children. The largest outbreak in the US was in 2014 with over 1,100 respiratory disease cases and associated with 120 AFM cases. Preliminary studies demonstrate that anti-EV-D68 antibodies can have activity against multiple EV-D68 viruses and are efficacious in animals models of both respiratory and neurologicdisease. The proposed work will achieve the following objectives: Determination of breadth of anti-EV-D68 mAb activity; Determination of in vivo efficacy of anti-EV-D68 mAb candidates and ead selection; Computational assessment and optimization of manufacturing liabilities of the lead candidates. At the completion of this proposed research, a lead anti-EV-D68 monoclonal antibody will be identified and optimized and ready to move forward in preclinical and manufacturing development of a monoclonal antibody drug against EV-D68 infection.
