ANTIIDIOTYPIC ANTIBODIES TO THE 3RD VARIABLE DOMAIN OF GP120 INDUCED AN ANTI-HIV-1 ANTIBODY-RESPONSE IN MICE

We tested the potential of anti-idiotypic antibodies to function as molecular mimics of a neutralizing epitope of the human immunodeficiency virus (HIV). Three monoclonal antibodies to the third variable domain (V-3) of gp120 from the HIV-1LAI isolate were raised in a BALB/c mouse. They bound gp120LAI with high affinity (K-d similar or equal to 10(-11) M), immunoprecipitated viral gp120LAI, recognized HIVLAI-infected cells by immunofluorescence and neutralized HIVLAI infection in vitro. Mice and rabbits were immunized against each one of these antibodies, and one monoclonal and two polyclonal anti-idiotypic reagents were selected for further study. The three anti-idiotypes recognized binding site-related idiotopes that were not present on other V-3-specific mouse sera or monoclonal antibodies. Groups of mice and rabbits were immunized against these anti-idiotypes presented in a homopolymerized form, conjugated to a protein carrier, or in an uncoupled form. In the absence of antigen, mice that received polyclonal anti-idiotypes mounted an antibody response to gp120LAI, but not to V-3-deleted gp120LAI recombinant proteins. Unlike the three nominal mAbs, the induced antibodies also reacted with gp120 from the divergent HIV strain SF2. The isotypic distribution of the anti-idiotype-induced antibodies and their temporal evolution resemble the restricted pattern and the rapid rise of the antibody response obtained after administration of recombinant gp120LAI to mice. These data thus present evidence that anti-idiotypes raised against HIV-specific antibodies may substitute viral antigens for induction of a humoral immune response to HIV. They also suggest that the HIV epitope variability may be, in part, overcome with the use of anti-idiotypic reagents. (C) 1994 Academic Press. Inc.