Passive immunotherapy has been shown to be an effective method for controlling RSV infection. The virus envelope fusion (F protein) represents an ideal target for passive immunotherapy because antibodies to this protein tYpically bind to and neutralize both of the two clinical subgroups of this virus, A and B. In addition, antibodies to the F protein have been shown to provide protection in animal models of RSV. We will produce human MAbs, which are capable of in vitro and in vivo neutralization and which are useful for the treatment of this significant pathogen. Human B cells will be immortalized using three approaches: EBV transformation, somatic cell fusion, and hu-SCID mouse expansion followed by EBV transformation. Immortalized human B cells will be screened for antibody activity to the F protein. F protein reactive B cells will be cloned and their antibodies tested for virus-neutralizing activity. The immunoglobulin genes from the selected B cell clones will be transfected into a mammalian expression system for generation of antibodies for clinical evaluation.Awardee's statement of the potential commercial applications of the research: The research will provide IDEC Pharmaceuticals Corp. with a human monoclonal antibody. The antibody can be used for the passive immunotherapy of respiratory syncytial virus infection in infants, the elderly and immunocompromised patients.National Institute of Allergy and Infectious Diseases (NIAID)