Nasal IGA for Respiratory Syncytial Virus Prophylaxis

Respiratory syncytial virus (RSV) appears in predictable yearly outbreaks. In most people, it causes mild upper respiratory tract disease, but in young infants and other high risk populations it can spread and cause bronchiolitis and pneumonia. RSV is now considered the major cause of lower respiratory tract disease in infants. The overall goal is to develop a monoclonal antibody (mAb) product for prevention of RSV infection in high risk individuals. The product will be formulated for nasal delivery to provide protection of the upper respiratory tract and will comprise one or more mAbs engineered to include murine antigen binding regions and human IgA constant regions. Candidate murine anti-RSV mAbs of IgA and IgG isotypes have been generated. Several protect against upper and lower respiratory tract infection in mice when delivered intranasally. In this Phase I study, we will examine mechanisms of protection and define optimal dose and schedule of mAb treatment. The results will form the basis for further product development including humanization, formulation for nasal delivery, and preclinical safety and efficacy studies in cotton rats and nonhuman primates.