Our laboratory has generated an anti-idiotype monoclonal antibody (mAb) AB194 to the HIV-1 neutralizing mAb BAT123 which recognized an immunodominant region of gpl2O. We have characterized AB19-4 to be a paratope-specific anti-Id mAb which 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 gpl2O and neutralizing activity toward HIV-1. AB19-4 is therefore a good candidate for AIDS vaccine development. 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 this Phase I application, we propose to use recombinant DNA techniques 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, we will further evaluate the anti-Id Fv protein 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.
