Attempts to make a practical HIV vaccine have so far been unsuccessful. Here, we propose using an anti-HIV receptor (CD4) antibody as an HIV vaccine to circumvent the current problems of HIV vaccine trials. The premise of our 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. We will generate a panel of murine anti-CD4 MAbs and characterize them 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. In phase 2, we 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.
