MONOCLONAL ANTIBODIES TO HTLV-III/LAV

MOUSE AND RAT MONOCLONAL ANTIBODIES WILL BE PRODUCED AGAINSTHTLV-III, THE HUMAN RETROVIRUS ASSOCIATED WITH AIDS AND A SPECTRUM OF RELATED SYNDROMES. GENE LABS WILL EMPLOY INTACTHTLV-III VIRIONS COUPLED TO KLH AS AN IMMUNOGEN AND USE A SENSITIVE ELISA ASSAY, BASED ON PURIFIED HTLV-III AS THE ANTIGEN IN OUR PRIMARY SCREENING PROCEDURE. IMMUNOPRECIPI- TATION, WESTERN BLOTTING, AND CELLULAR IMMUNOFLUORESCENCE WILL BE USED TO CHARACTERIZE STABLE, IMMUNOGLOBULIN- SECRETING, ELISA-REACTIVE SUBCLONES. ANTIBODY BINDING CONSTANTS WILL BE ASSESSED BY STANDARD PROCEDURES. FINE MAPPING OF ANTIBODY SPECIFICITY AS IT CORRELATES WITH BIOLOGICAL EFFECTS WILL BE EXAMINED IN THE CONTEXT OF SEPARATE PHASE II FUNDING. PRELIMINARY STUDIES HAVE DEMONSTRATED THE FEASIBILITY OF THE PROPOSAL APPROACH, RESULTING IN THE GENERATION OF BOTH MOUSE AND RAT MONOCLONALANTIBODIES TO HTLV-III DETERMINED ANTIGENS. THE SUCCESSFUL COMPLETION OF THIS PROJECT WILL INVOLVE THE ESTABLISHMENT OFA COMPLETE PANEL OF RAT AND MOUSE MONOCLONAL ANTIBODIES WITHHIGH AVIDITY AGAINST EPITOPES THAT MAY BE WEAKLY IMMUNOGENICOR SILENT IN THE NORMAL HOST.