EXPRESSION OF AN ANTI-IDIOTYPIC FV FRAGMENT AS A VACCINE FOR AIDS

TANOX BIOSYSTEMS, INC., HAS GENERATED AN ANTI-IDIOTYPE (ID) MONOCLONAL ANTIBODY (MAB), AB19-4, TO THE HIV-1-NEUTRALIZING MAB, BAT123, WHICH RECOGNIZES AN IMMUNODOMINANT REGION OF GP120. RESEARCH HAS CHARACTERIZED AB19-4 TO BE A PARATOPE-SPECIFIC ANTI-ID MAB THAT MIMICS THE THREE-DIMENSIONAL STRUCTURE OF NEUTRALIZING EPITOPES OF THE VIRUS. FURTHERMORE, POLYCLONAL RESPONSES OBTAINED FROM RABBITS IMMUNIZED WITH AB19-4 SHOWED SPECIFIC IMMUNOREACTIVITY TO GP120 AND NEUTRALIZING ACTIVITY TOWARD HIV-1. AB19-4 IS, THEREFORE, A GOOD CANDIDATE FOR AIDS VACCINE DEVELOPMENT. HOWEVER, DIRECT USE OF MURINE MAB AB19-4 IN VIVO MAY POSE A PROBLEM DUE TO THE IMMUNOGENICITY OF THE CONSTANT REGIONS OF THE MOLECULE. IN PHASE I, RECOMBINANT DNA TECHNIQUES WILL BE USED TO PRODUCE THE CORRESPONDING FV FRAGMENT FOR ITS POTENTIAL USE AS A VACCINE. THIS PROCESS WILL INVOLVE CLONING THE VARIABLE REGION GENES ENCODING BOTH HEAVY AND LIGHT CHAINS OF THE MURINE IGG AND SPLICING THEM INTO A BACTERIAL EXPRESSION VECTOR. BOTH CHAINS WILL BE CO-EXPRESSED, AND ASSEMBLED PROTEINS WILL BE CHARACTERIZED. IN PHASE II STUDIES, THE ANTI-ID FV PROTEIN WILL BE FURTHER EVALUATED AS A POTENTIAL CANDIDATE FOR DEVELOPMENT INTO AN AIDS VACCINE. IF PROVEN FEASIBLE, THIS TECHNOLOGY CAN BE BROADLY APPLICABLE TO ALL ANTI-ID-BASED THERAPY.