ANTI-ID ANTIBODY VACCINE FOR HUMAN RESPIRATORY SYNCYTIAL VIRUS

RESPIRATORY SYNCYTIAL VIRUS (RSV) IS NOW RECOGNIZED AS THE LEADING CAUSE OF HOSPITALIZATION OF CHILDREN DURING THE FIRST YEAR OF LIFE AS WELL AS THE LEADING CAUSE OF PEDIATRIC NOSCOMIAL INFECTION. THE INFECTION CARRIES AN ASSOCIATION MORTALITY RATE OF 0.5%, AND RECENT ESTIMATED BY TH INSTITUTE OF MEDICINE PLACE THE NUMBER OF HOSPITALIZATIONS IN THE U.S. SECONDARY TO RSV INFECTION AT APPROXIMATELY 91,000 ANNUALLY. THE ASSOCIATED MEDICAL COST OF THE DISEASE IS ROUGHLY $300,000,000. VACCINATION ATTEMPTS TO PREVENT INFECTION HAVE UNIFORMLY FAILED. INDEED, CONVENTIONAL VACCINE METHODOLOGY RESULTED IN MORE SEVERE RESPIRATORY MANIFESTATIONS IN VACCINE RECIPIENTS COMPARED TO UNVACCINATED CONTROLS. INTRA-NASAL ANTI-IDIOTYPIC (ANTI-ID) VACCINATION, ON THE OTHER HAND, SEEMS IDEALLY SUITED TO GENERATE PASSIVE IMMUNITY IN THE NASAL MUCOSA OF AT RISK INFANTS. THE FUSION (F) PROTEIN OF THE VIRUS IS LARGELY (IF NOT ENTIRELY) RESPONSIBLE FOR THE INFECTIVITY OF RSV, AND IS KNOWN TO POSSESS NOR MORE THAN FOUR NEUTRALIZING EPITOPES. NEUTRALIZING ANTIBODIES TO THE F PROTEIN OF BOVINE RSV HAVE RECENTLY BEEN REPORTED (KLUCAS AND ANDERSON, 1988). SINCE SUBSTANTIAL HOMELOGY EXISTS BETWEEN THE F PROTEIN OF BRSV AND HRSV, WE WILL UTILIZE THESE ANTIBODIES TO GENERATE A HUMAN ANTI-ID TO UTILIZE AS A VACCINE FOR INFANTS. WE HAVE GENERATED ANTI-ID ANTIBODIES AGAINST THESE ANTI-F ANTIBODIES, AND HAVE SHOWN THAT HUMAN SERA (RECENTLY EXPOSED TO RSV) RECOGNIZES THE MURINE ANTI-IDS. WE HAVE FURTHER SHOWN THAT THIS BINDING IS INHIBITED BY ANTI-F. THE IMPLICATION OF THESE RESULTS IS THAT HUMAN SERA CONTAIN ANTIBODIES ANALOGOUS TO THE ORIGINAL ANTI-F. WE WILL CREATE HYBRIDOMAS WHICH SECRETE HUMAN ANTIBODIES AGAINST ANTI-F TO BE UTILIZED AS AN INTRA-NASAL VACCINE.