NEUTRALIZATION OF HIV

MONOCLONAL ANTIBODIES HAVE BEEN GENERATED WHICH REACT WITH CONSERVED SITES OF THE P17 CORE PROTEIN OF THE HUMAN IMMUNODEFICIENCY VIRUS (HIV). TWO OF THESE ANTIBODIES EXERTA POTENT NEUTRALIZING EFFECT ON THE REPLICATION OF HIV IN PERMISSIVE CELLS. THE GOALS OF THIS PROPOSAL ARE TO (1) PRECISELY IDENTIFY THE P17 EPITOPES RECOGNIZED, (2) SYNTHESIZE PEPTIDES WHICH SPAN THE EPITOPES OF INTEREST, (3) GENERATE IDIOTYPIC REAGENTS CORRESPONDING TO THE BIOLOGICALLY ACTIVE ANTIBODIES AND TO (4) CHARACTERIZE THE ANTIPEPTIDE ANTISERA AND IDIOTYPIC ANTIBODIES FOR HIV NEUTRALIZATION AND INHIBITION OF VIRAL ADSORPTION TO TARGET RECEPTORS. METHODOLOGIES FOR ACHIEVING THESE GOALS INCLUDE EPITOPE MAPPING, PEPTIDE SYNTHESIS, MONOCLONAL AND POLYCLONAL ANTIBODY DEVELOPMENT AND THE USE OF HIV TRANSMISSION ASSAYS AND VIRAL ADSORPTION PROCEDURES. A COMPARATIVE EVALUATION OF THE BIOLOGICAL EFFICACY OF ANTIPEPTIDE VERSUS IDIOTYPIC ANTIBODIES WILL RESULT, ALONG WITH INFORMATION RELATING TO NOVEL SITES ON HIV STRUCTURES WHICH ARE AMENABLE TO NEUTRALIZATION.