THE ANTI-IDIOTYPE ANTIBODY APPROACH FOR AN HIV VACCINE

ATTEMPTS TO MAKE A PRACTICAL HIV VACCINE HAVE BEEN UNSUCCESSFUL TO DATE. WE WILL USE ANTI-IDIOTYPE ANTIBODY (ANTI-ID) AS AN HIV VACCINE TO ELICIT HIGH TITERS OF GROUP-SPECIFIC NEUTRALIZING ANTIBODIES. THE PRINCIPLE OF THIS APPROACH IS BASED ON IDIOTYPE MATCHING, WHICH UTILIZES ANTI-IDS AS SURROGATES FOR ANTIGEN IN AN ATTEMPT TO STIMULATE SPECIFIC ELEMENTS OF THE B CELL REPERTOIRE IN HUMANS. THE APPLICANT WILL GENERATE AND CHARACTERIZE A PANEL OF MURINE ANTI-ID MABS AGAINST HUMAN POLYCLONAL ANTI-GP120 ANTIBODIES. THE CHARACTERIZATION OF ANTI-ID MABS WILL BE ACHIEVED BY AFFINITY ISOLATION WITH INDIVIDUAL ANTI-ID MABS WHICH INTERACT WITH GROUP SPECIFIC NEUTRALIZING ANTI-GP120 ANTIBODIES FOR FURTHER STUDIES IN PRIMATES. TO IDENTIFY ANTI-ID MABS OF POTENTIAL UTILITY IN ELICITING GROUP-SPECIFIC NEUTRALIZING ANTIBODIES, MONKEYS WILL BE IMMUNIZED WITH ANTI-ID MABS AND THE SERA WILL BE EVALUATED FOR NEUTRALIZING ANTI-GP120 ANTIBODIES. EVALUATION OF NEUTRALIZING ANTIBODIES WILL BE DONE BY MEASUREMENT OF ANTI- GP120 TITER IN ELISA AND VIRUS NEUTRALIZATION ASSAY USING VARIOUS HIV ISOLATES. IN PHASE II, PROTECTION EXPERIMENTS AGAINST VIRAL INFECTION IN PRIMATES AND FURTHER EVALUATION OF ANTI-ID MABS AS AN HIV VACCINE IN HUMANS, WILL BE PERFORMED.