Monoclonal Antibodies to Respiratory Syncytial Virus

Respiratory syncytial virus (RSv) is the primary etiologic agent of pediatric respiratory tractinfection. In premature infants and children with bronchopulmonary dysplasia or congenital heartdisease, RSv induced pneumonia and bronchiolitis cause significant morbidity and mortality. ProphylacticRSv vaccines are not available and the use of Ribavirin, an approved treatment for RSv infection, hasproven to be controversial. Currently the most promising approach to prophylaxis and treatment of RSvdisease in high risk cases is passive immunization. A hyperimmune intravenous immunoglobulin (IVIG)product for the prevention of RSv disease has been shown to be extremely effective in a Phase III clinicaltrial. The development of a standardized, defined product with higher specific activity would lower costsand enhance ease of administration and, thus, have increased use in populations at risk. Our objectivesare to generate potent neutralizing human monoclonal antibodies to the more conserved fusion (F)glycoprotein of RSv in the HyPBL-SCID mouse (severe combined immunodeficient mice reconstitutedwith human Peripheral blood lymphocytes) immunized with RSv. Selection of antibodies by their abilityto neutralize a panel of clinical isolates in vitro and in vivo models will form the basis of a Phase II study.