ANTI-CD4 ANTIBODY AS A THERAPEUTIC AND PREVENTIVE HIV VACCINE

ATTEMPTS TO MAKE A PRACTICAL HIV VACCINE HAVE SO FAR BEEN UNSUCCESSFUL. THIS RESEARCH WILL USE AN ANTI-HIV RECEPTOR (CD4) ANTIBODY AS AN HIV VACCINE TO CIRCUMVENT THE CURRENT PROBLEMS OF HIV VACCINE TRIALS. THE APPROACH IS BASED UPON THE ASSUMPTION THAT CERTAIN ANTI-CD4 ANTIBODIES CAN STRUCTURALLY MIMIC THE NEUTRALIZING EPITOPE OF GP120 AND ELICIT NEUTRALIZING ANTI-GP120 ANTIBODIES. A PANEL OF MURINE ANTI-CD4 MONOCLONAL ANTIBODIES (MABS) WILL BE GENERATED AND CHARACTERIZED IN VITRO TO IDENTIFY CANDIDATES FOR GP120-MIMICKING ANTIBODIES BY EPITOPE MAPPING AND IN VITRO VIRUS NEUTRALIZATION ASSAYS. BASED UPON IN VITRO CHARACTERIZATIONS, ANTI-CD4 MABS WILL BE SELECTED AND EVALUATED IN VIVO TO IDENTIFY THEIR POTENTIAL UTILITY IN ELICITING NEUTRALIZING ANTI-GP120 ANTIBODIES AGAINST VARIOUS HIV ISOLATES. FOR THIS, RABBITS AND RATS WILL BE IMMUNIZED WITH ANTI-CD4 MABS, AND THE SERA WILL BE EVALUATED FOR NEUTRALIZING ANTI-GP120 ANTIBODIES BY MEASUREMENT OF ANTI-GP120 TITER IN ELISA AND VIRUS NEUTRALIZATION ASSAYS USING VARIOUS HIV ISOLATES. PHASE II RESEARCH WILL FURTHER EVALUATE THE EFFECT OF ANTI-CD4 MABS AS AN HIV VACCINE IN PRIMATES. AT THAT TIME, PROTECTION EXPERIMENTS AGAINST VIRAL INFECTION WILL BE PERFORMED.