HUMAN-MURINE CHIMERIC ANTIBODIES VS. RESPIRATORY SYNCYTIAL VIRUS

RESPIRATORY SYNCYTIAL VIRUS (RSV) IS RESPONSIBLE FOR YEARLY EPIDEMICS OF BRONCHIOLITIS AND PNEUMONIA IN INFANTS AND YOUNG CHILDREN. AT RISK OF SERIOUS RSV MORBIDITY ARE CHILDREN WITH UNDERLYING DISEASE, BRONCHOPULMONARY DYSPLASIA AND OTHER PULMONARY DISEASES, VARIOUS CONGENITALOR ACQUIRED IMMUNODEFICIENCY SYNDROMES AND PREMATURITY. A VACCINE FOR IMMUNIZATION TO PREVENT RSV INFECTIONS IS URGENTLY NEEDED. UNFORTUNATELY, RSV VACCINES ARE UNLIKELY TO BE LICENSED IN THE NEAR FUTURE. THE INITIAL FORMALIN INACTIVATED RSV VACCINE CAUSED AN INCREASED INCIDENCE OFRSV LOWER RESPIRATORY TRACT DISEASE AND DEATH IN IMMUNIZED CHILDREN. THEREFORE, THE MOST PROMISING APPROACH TO PROPHYLAXIS OF RSV DISEASE IN HIGH RISK INFANTS IS PASSIVE IMMUNIZATION. CURRENTLY, INTRAVENOUS HYPERIMMUNE GLOBULIN PREPARED FROM PLASMA CONTAINING HIGH LEVELS OF ANTI-RSV ANTIBODY IS BEING TESTED IN HIGH RISK CHILDREN FOR PROTECTIVE EFFICACY. HOWEVER, A MORE RELIABLE SOURCE OF A HIGHLY DEFINED AND STANDARDIZED PRODUCT WOULD BE DESIRABLE. MURINE MABS AGAINST THE F GLYCOPROTEIN OF RSV HAVE BEEN DEVELOPED AND CHARACTERIZED. THESE HAVE BEEN SHOWN TO NEUTRALIZE RSV IN VITRO AND PROTECT COTTON RATS FROM LOWER RESPIRATORY TRACT INFECTIONIN VIVO. PREVIOUS STUDIES WITH OTHER RODENT ANTIBODIES SUGGEST THAT THE DEVELOPMENT OF HUMAN ANTI-MOUSE ANTIBODY RESPONSES WOULD PRECLUDE THE USE OF THESE MURINE ANTIBODIES DIRECTLY IN CHILDREN. THEREFORE, IT IS THE OBJECTIVE OF THIS PHASE I STUDY TO DEVELOP HUMANIZED DERIVATIVES OF THESE ANTI-RSV ANTIBODIES WHICH COULD THEN BE DEVELOPED AS AGENTS FOR PASSIVE IMMUNIZATION AGAINST RSV INFECTION.